High-flow nasal oxygen versus noninvasive ventilation in acute respiratory failure: reflections on the RENOVATE trial

We read the recent RENOVATE trial in the December 10th, 2024 edition of the Journal of the American Medical Association with great interest (1).This study adds to a growing body of literature exploring the use of highflow nasal oxygen (HFNO) compared with noninvasive ventilation (NIV) in acute respiratory diseases (2-4).Specifically, RENOVATE was a randomized controlled trial of 1,766 patients comparing the use of HFNO versus NIV for those with hypoxemia and five different clinical conditions: immunocompromised state, nonimmunocompromised state, acute cardiogenic pulmonary oedema (ACPO), chronic obstructive pulmonary disease (COPD) exacerbation with respiratory acidosis, and coronavirus disease 2019 (COVID-19).Many of these diseases would traditionally be managed with NIV (particularly ACPO and COPD with respiratory acidosis), rather than HFNO, owing to a wealth of robust literature and experience in support of this approach in these clinical conditions (5,6).While this study demonstrated noninferiority of HFNO with respect to the primary outcome of endotracheal intubation and 7-day mortality in all but the immunocompromised cohorts, discussion regarding the limitations of this study and its place within the context of existing literature on the topic is necessary to understand how it may influence patient care.This study supports the superiority of HFNO for patient comfort in instances of acute respiratory failure (ARF) as compared with NIV.Patients receiving HFNO reported significantly higher comfort scores at every interval, and sedative use was more frequent in all NIV groups, particularly among patients with COVID-19 (7).This finding is clinically meaningful, as intolerance of NIV is a common driver of treatment failure, escalation to intubation, increased sedative exposure, and prolonged intensive care unit length of stay.Importantly, sedative use is not benign and carries increased risk of adverse outcomes, including delirium, hypotension, and bradycardia (8).These risks may be mitigated through use of a more tolerable respiratory support modality when clinically appropriate.Despite these advantages, the generalizability of the RENOVATE trial is constrained by the mild-to-moderate severity of illness across cohorts.In the ACPO group, patients had partial pressure of oxygen in arterial blood (PaO 2 ) to fraction of inspired oxygen (FiO 2 ) ratios of 247 in the HFNO arm and 235 in the NIV arm.Moreover, patients requiring NIV prior to randomization were excluded,