High-flow nasal oxygen vs. conventional oxygen therapy in patients with COVID-19 related acute hypoxemic respiratory failure and a do not intubate order: a multicentre cohort study

Abstract

Background: High-flow nasal oxygen (HFNO) is frequently used to treat patients with acute hypoxemic respiratory failure (AHRF) due to viral pneumonia, including COVID-19. However, its clinical effect compared to conventional oxygen therapy (COT) remains largely unexplored in patients with a do not intubate (DNI) order. We aimed to assess whether HFNO compared to COT is associated with improved clinical outcomes in hospitalized patients with AHRF due to COVID-19 and a DNI order.

Methods: This analysis included patients with a DNI order and SARS-CoV-2 infection, selected from three observational studies, who were treated with COT only or HFNO. The primary endpoint was in-hospital mortality, the secondary endpoint was hospital length of stay (LOS). The effect of HFNO vs. COT was assessed using multivariable regression, accounting for pre-selected confounders.

Results: Between March 2020 and September 2021, 116 patients received HFNO and 110 patients received COT. Median age was 78 [72-83], and 78% of the patients had a Clinical Frailty Scale score of 4 to 9. In-hospital mortality was 64% for HFNO and 71% for COT (p = 0.29), with an adjusted odds ratio of 0.72 (95% confidence interval [0.34-1.54], p = 0.40). Hospital LOS was 11 [6-18] days for HFNO, and 7 [4-12] days for COT (p < 0.001), with a remaining difference after adjusting for confounders (p < 0.01).

Conclusion: The lack of survival benefit and increased hospital LOS should be taken into account when considering HFNO for patients with a DNI order, suffering from AHRF due to viral pneumonia, like COVID-19.

Clinical trial registration: HFNO-COVID-19 study: DTR, NL9067 (Dutch Trial Registry), registration date: 27-11-2020.

Keywords: Acute hypoxemic respiratory failure; COVID-19; Conventional oxygen therapy; Do not intubate order; High-flow nasal oxygen.

Fig. 1

Flowchart study population. Cohort 1 refers to the HFNO-COVID-19 cohort, cohort 2 refers to the Northwest Hospital group (NWZ) cohort, cohort 3 refers to the University Medical Center Groningen (UMCG) cohort. HFNO high-flow nasal oxygen, COT conventional oxygen therapy

Fig. 2

Kaplan–Meier curve of HFNO vs. COT. HFNO high-flow nasal oxygen, COT conventional oxygen therapy. a Kaplan–Meier Curve of HFNO vs. COT (time point selected as potential HFNO initiation point for COT: at least 6 L oxygen per minute), log-rank p-value: 0.02. b Kaplan–Meier Curve of HFNO vs. COT (time point selected as potential HFNO initiation point for COT: at maximum oxygen therapy level during hospital admission). Log-rank p-value: 0.002

Fig. 3

Course of respiratory parameters between survivors and non-survivors. a Respiratory rate, b Oxygen saturation, c S/F ratio, d ROX index. Parameters are depicted as Boxplot, p-values: Mann–Whitney U-test for continuous variables and Chi-square test for categorical variables. * represent p-values < 0.05, ** represent p-values < 0.001. T time point, prior prior to HFNO initiation, Q quartile, IQR interquartile range, S/F ratio SpO₂/FiO₂ ratio, ROX index respiratory oxygenation index (SpO₂/FiO₂/respiratory rate)