The utility of high-flow nasal oxygen for severe COVID-19 pneumonia in a resource-constrained setting: A multi-centre prospective observational study

Abstract

Background: The utility of heated and humidified high-flow nasal oxygen (HFNO) for severe COVID-19-related hypoxaemic respiratory failure (HRF), particularly in settings with limited access to intensive care unit (ICU) resources, remains unclear, and predictors of outcome have been poorly studied.

Methods: We included consecutive patients with COVID-19-related HRF treated with HFNO at two tertiary hospitals in Cape Town, South Africa. The primary outcome was the proportion of patients who were successfully weaned from HFNO, whilst failure comprised intubation or death on HFNO.

Findings: The median (IQR) arterial oxygen partial pressure to fraction inspired oxygen ratio (P_aO2/FiO₂) was 68 (54-92) in 293 enroled patients. Of these, 137/293 (47%) of patients [P_aO2/FiO₂ 76 (63-93)] were successfully weaned from HFNO. The median duration of HFNO was 6 (3-9) in those successfully treated versus 2 (1-5) days in those who failed (p<0.001). A higher ratio of oxygen saturation/FiO2 to respiratory rate within 6 h (ROX-6 score) after HFNO commencement was associated with HFNO success (ROX-6; AHR 0.43, 0.31-0.60), as was use of steroids (AHR 0.35, 95%CI 0.19-0.64). A ROX-6 score of ≥3.7 was 80% predictive of successful weaning whilst ROX-6 ≤ 2.2 was 74% predictive of failure. In total, 139 patents (52%) survived to hospital discharge, whilst mortality amongst HFNO failures with outcomes was 129/140 (92%).

Interpretation: In a resource-constrained setting, HFNO for severe COVID-19 HRF is feasible and more almost half of those who receive it can be successfully weaned without the need for mechanical ventilation.

Keywords: COVID-19; High flow nasal oxygen; Pneumonia; Ventilation.

Fig. 1

CONSORT diagram showing outcomes of HFNO and survival to discharge. HFNO: high-flow nasal cannula oxygen; ICU: intensive care unit; MV: mechanical ventilation, DNR: do not resuscitate. Success = weaned from HFNO; Failure= need for intubation or death. * Triaged due local facility protocol, DNR order or pre-specified patient preference. ^† Survival to hospital discharge = 139/269 (52%): denominator excludes those still in hospital or ventilated in ICU (n = 24). ^†† Sudden death = abrupt unexpected death on HFNO (intubation was not being considered at the time).

Fig. 2

Proportion of patients on HFNO reaching outcome per day of therapy. The median (IQR) duration of HFNO was 6 (3–9) days in those successfully treated versus 2 (1–5) days in those who failed (p<0.001). *P<0.05 when compared to proportion of previous day for same outcome (Pearson's χ² test).

Fig. 3

A. Receiver operating characteristic (ROC) curve for ROX-6 for predicting HFNO failure. ROC was performed for ROX-6 (134 patients successfully treated with HFNO and 145 patients who failed HFNO). Area under the curve (AUC) for ROX-6 is 0.75 with p<0.0001. B. Scatter plot of ROX score (ratio of oxygen saturation/FiO2 to respiratory rate) at 6 h (ROX-6) showing cut-offs maximising sensitivity and specificity. PPV = positive predictive value; NPV = negative predictive value. A ROX-6 below 3.7 (cut-off A, maximising sensitivity) was 90% sensitive (true positives) whilst ROX-6 above 2.2 (cut-off B, maximising specificity) was 90% specific (true negatives). The single cut-off that maximised sensitivity and specificity (Youden's index) was 2.7; the PPV and NPV at Youden's index was 72% and 73%, respectively.