Derivation and Exploratory Evaluation of the Respiratory Rate-Oxygenation (ROX) Index as a Predictor of High-Flow Nasal Cannula Outcomes in Patients With COVID-19 Pneumonia

Objectives: High-flow nasal cannula (HFNC) therapy is a first-line respiratory support modality for acute hypoxemic respiratory failure (AHRF) due to COVID-19 pneumonia. The respiratory rate-oxygenation (ROX) index, defined as the ratio of peripheral oxygen saturation (SpO2)/fraction of inspired oxygen (FiO2) divided by respiratory rate, has been proposed as a predictor of HFNC success or failure. This study aimed to derive time-specific cut-off values and explore the predictive accuracy of the ROX index in COVID-19 patients receiving HFNC therapy. Methods: This single-center prospective observational cohort study included 60 consecutive adult patients with COVID-19 pneumonia requiring HFNC therapy in the intensive care unit (ICU) from March 2021 to February 2022. The study was conducted at Medanta, Ranchi, India. The ROX index was measured at 2, 6, 12, 18, and 24 hours after HFNC initiation. HFNC failure was defined as the subsequent requirement for invasive mechanical ventilation (IMV) within the index ICU admission. Receiver operating characteristic (ROC) curves with optimal cut-off determined by the Youden index, and univariate logistic regression were used to assess predictive accuracy. Results: Of 60 patients enrolled, 37/60 (61.7%) achieved HFNC success, and 23/60 (38.3%) experienced HFNC failure. The ROX index was significantly higher in the success group at all measured time points (P<0.001). The ROX index at 12 hours was the best predictor of HFNC outcome (area under the curve (AUC)=0.973, sensitivity 36/37 (97.3%), specificity 19/23 (82.6%), cut-off value 5.81). These performance estimates were derived and evaluated in the same 60-patient cohort and should be considered optimistic pending external validation. Univariate logistic regression showed odds ratios up to 102 at 24 hours. Vaccination was present in 25/60 patients (41.7%) and showed a non-significant trend toward association with HFNC success (chi-square 3.72, P=0.054). Mortality was 18/23 (78.3%) in the failure group versus 0/37 (0%) in the success group (P<0.001). Conclusions: The ROX index is a candidate non-invasive bedside predictor of HFNC therapy outcome in patients with COVID-19 pneumonia. Derived cut-offs, particularly at 12 hours (5.81), showed promising predictive accuracy and can aid clinicians in timely decisions regarding escalation to IMV. These findings are hypothesis-generating and require external validation before clinical implementation.