Noninvasive Treatment of Hypoxemic Respiratory Failure: Give It a Try… But Do Not Push Too Hard*

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Noninvasive support of ICU patients presenting with acute hypoxemic respiratory failure (AHRF) is used with increasing frequency (1) following the rediscovery of noninvasive ventilation (NIV) in the late 1980s and the more recent commercialization of devices allowing administration of humidified high-flow nasal oxygen.
Nearly 2 decades after two landmark randomized controlled trials (performed before the era of protective ventilation) reported a mortality benefit of NIV in immunocompromised patients with AHRF (2, 3), a contemporary large randomized controlled trial has raised new uncertainty regarding the benefit of NIV (4).
Although no multicenter randomized controlled trial unequivocally supports the use of NIV in the general population of patients with AHRF or acute respiratory distress syndrome (ARDS), a high rate of failure (up to 50%) of this technique has been repeatedly reported (5–7). Furthermore, an “increased” mortality related to NIV use in ARDS was suggested in the recent LUNG SAFE study in the subgroup of patient with PaO2/FIO2 ratio below 150 mm Hg (7).
On the other hand, nasal high-flow oxygen therapy has recently emerged as a promising therapy of AHRF. Investigators of the FLORALI trial randomized 310 patients with AHRF—patients with respiratory rate greater than 25/min and without extrarespiratory organ dysfunction—into a nasal high-flow oxygen therapy group, an NIV group, and a conventional face-mask oxygen therapy group (8). Although no difference was found in intubation rate (the primary endpoint), the count of ventilator-free days at day 28 was significantly higher and the mortality at day 90 was significantly lower in the nasal high-flow oxygen group. A post hoc analysis identified a lower intubation rate favoring nasal high-flow oxygen therapy in the subgroup of patients with PaO2/FIO2 ratio lower than 200 mm Hg. These are exploratory findings, and therefore, confirmation in a prospective randomized trial is required. We observe that patient comfort is important: nasal high-flow oxygen therapy significantly improved patient comfort and dyspnea score as compared to the other techniques, emphasizing the potential of this technique to improve patient-centered outcomes. Furthermore, in immunocompromised patients with AHRF, several exploratory studies favor nasal high-flow oxygen therapy over NIV for decreasing intubation rate (9, 10). Several randomized controlled trials are underway to confirm this finding.
In this issue of Critical Care Medicine, investigators, Frat et al (11), who conducted the FLORALI trial present a secondary analysis of their data. They aimed to identify early predictors of failure (defined as intubation within the following 28 days) in patients with AHRF initially treated with noninvasive oxygen therapy. Evaluation of these failures is important since noninvasive management of AHRF has been asserted to be harmful in the subgroup of patients who fail to improve under that initial noninvasive therapy and are subsequently intubated (7, 12), with harms attributed to delay of appropriate diagnostic and/or needed therapeutic management.
The size of the FLORALI study population, the multicentricity, and the prospective design make this cohort particularly informative. Here are the key findings: Respiratory rate greater than 30/min 1 hour after randomization and higher heart rate 1 hour after randomization now emerge as independent predictors of failure for standard oxygen therapy and for high-flow nasal oxygen therapy, respectively. NIV failure was independently associated with both PaO2/FIO2 ratio less than 200 mm Hg and expired tidal volume exceeding 9 mL/kg 1 hour after initiation of the technique.
Perhaps the key message of this secondary analysis lies not in the predictors of noninvasive oxygen therapy failure that were identified, but rather in the inability to find any useful predictor prior to attempting a noninvasive therapy of any sort. Indeed, no patient characteristic could predict subsequent intubation before initiation of any of the three techniques.

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