The Effectiveness of High-Flow Nasal Cannula in Coronavirus Disease 2019 Pneumonia: A Retrospective Cohort Study

Abstract

Objectives: High-flow nasal cannula is widely used in acute hypoxemic respiratory failure due to coronavirus disease 2019, yet data regarding its effectiveness is lacking. More evidence is needed to guide patient selection, timing of high-flow nasal cannula initiation, and resource allocation. We aimed to assess time to discharge and time to death in severe coronavirus disease 2019 in patients treated with high-flow nasal cannula compared with matched controls. We also evaluated the ability of the respiratory rate-oxygenation ratio to predict progression to invasive mechanical ventilation.

Design: Time-dependent propensity score matching was used to create pairs of individuals who were then analyzed in a Cox proportional-hazards regression model to estimate high-flow nasal cannula's effect on time to discharge and time to death. A secondary analysis excluded high-flow nasal cannula patients intubated within 6 hours of admission. A Cox proportional-hazards regression model was used to assess risk of invasive mechanical ventilation among high-flow nasal cannula patients stratified by respiratory rate-oxygenation.

Setting: The five hospitals of the Johns Hopkins Health System.

Patients: All patients who were admitted with a laboratory-confirmed diagnosis of coronavirus disease 2019 were eligible for inclusion.

Interventions: None.

Measurements and main results: High-flow nasal cannula was associated with longer median time to discharge: 10.6 days (interquartile range, 7.1-15.8 d) versus 7.8 days (interquartile range, 4.9-12.1 d). Respiratory rate-oxygenation index performed poorly in predicting ventilation or death. In the primary analysis, there was no significant association between high-flow nasal cannula and hazard of death (adjusted hazard ratio, 0.79; 95% CI, 0.57-1.09). Excluding patients intubated within 6 hours of admission, high-flow nasal cannula was associated with reduced hazard of death (adjusted hazard ratio, 0.67; 95% CI, 0.45-0.99).

Conclusions: Among unselected patients with severe coronavirus disease 2019 pneumonia, high-flow nasal cannula was not associated with a statistically significant reduction in hazard of death. However, in patients not mechanically ventilated within 6 hours of admission, high-flow nasal cannula was associated with a significantly reduced hazard of death.

Figure 1.

Patient cohort and controls. HFNC = high-flow nasal cannula, JHHS = Johns Hopkins Health System.

Figure 2.

Primary analyses of mortality according to high-flow nasal cannula (HFNC) exposure. These Kaplan-Meier curves depict cumulative survival in (A) patients with any HFNC exposure and their matched controls as well as in (B) HFNC patient not intubated within 6 hr of admission and their matched controls. p value of less than 0.05 for comparison between HFNC patients not intubated within 6 hr of admission and their matched controls. aHR = adjusted hazard ratio.

Figure 3.

Primary analyses of mortality according to high-flow nasal cannula (HFNC) exposure, stratified by degree of hypoxemia. Similar to Figure 2, these Kaplan-Meier curves depict cumulative survival in patients with any HFNC exposure and in HFNC patients not intubated within 6 hr of admission as well as their respective matched controls. However, in this iteration, patients have also been matched by their degree of hypoxemia (ratio of oxygen saturation/Fio₂ [S/F] > 200 or < 200). p value of less than 0.05 for comparison between the more hypoxemic HFNC patients not intubated within 6 hr of admission and their matched controls. aHR = adjusted hazard ratio.

Figure 4.

Cumulative discharge rates. This figure demonstrates that time to discharge was significantly longer among high-flow nasal cannula (HFNC) patients. However, cumulative discharge rates begin to converge between days 14 and 21. aHR = adjusted hazard ratio.