Rationale: One important concern during high-flow nasal cannula (HFNC) therapy in patients with acute hypoxemic respiratory failure is to not delay intubation. Objectives: To validate the diagnostic accuracy of an index (termed ROX and defined as the ratio of oxygen saturation as measured by pulse oximetry/Fi_O₂ to respiratory rate) for determining HFNC outcome (need or not for intubation). Methods: This was a 2-year multicenter prospective observational cohort study including patients with pneumonia treated with HFNC. Identification was through Cox proportional hazards modeling of ROX association with HFNC outcome. The most specific cutoff of the ROX index to predict HFNC failure and success was assessed. Measurements and Main Results: Among the 191 patients treated with HFNC in the validation cohort, 68 (35.6%) required intubation. The prediction accuracy of the ROX index increased over time (area under the receiver operating characteristic curve: 2 h, 0.679; 6 h, 0.703; 12 h, 0.759). ROX greater than or equal to 4.88 measured at 2 (hazard ratio, 0.434; 95% confidence interval, 0.264-0.715; P = 0.001), 6 (hazard ratio, 0.304; 95% confidence interval, 0.182-0.509; P < 0.001), or 12 hours (hazard ratio, 0.291; 95% confidence interval, 0.161-0.524; P < 0.001) after HFNC initiation was consistently associated with a lower risk for intubation. A ROX less than 2.85, less than 3.47, and less than 3.85 at 2, 6, and 12 hours of HFNC initiation, respectively, were predictors of HFNC failure. Patients who failed presented a lower increase in the values of the ROX index over the 12 hours. Among components of the index, oxygen saturation as measured by pulse oximetry/Fi_O₂ had a greater weight than respiratory rate. Conclusions: In patients with pneumonia with acute respiratory failure treated with HFNC, ROX is an index that can help identify those patients with low and those with high risk for intubation. Clinical trial registered with www.clinicaltrials.gov (NCT02845128).

	Year	Citations

About