Editorial

Is a “Fine Tuning” of the Flow Rate During High Flow Oxygen Therapy Clinically Relevant?: The Optimal Setting of High Flow Nasal Cannula Should Be Explored Further

Alessandro Galazzi, Giacomo Grasselli

Chest 2025; 167: 1257-1258

The clinical effects of high flow nasal cannula (HFNC) include improvement of oxygenation, reduction of respiratory rate, inspiratory effort and dyspnea, amelioration of ventilation homogeneity and preservation of mucociliary function.¹ It has been shown that the magnitude of these effects is influenced by the system settings, particularly the Fio₂ (from 21% to 100%), the flow rate (from 30 L/min to 60 L/min), and the humidification temperature (from 31 °C to 37 °C) of the inspired gas mixture, which are decided respectively on the basis of the level of oxygenation, the level of dyspnea, and the need of humidification.² In addition, the optimal setting of HFNC may be different in different categories of patients (eg, patients with acute hypoxemic respiratory failure vs patients with hypercapnic exacerbation of a chronic respiratory condition).³ Most studies have explored the physiologic effects of different HFNC settings, although data on their impact on clinical outcomes are scarce.

In this issue of CHEST, Ruan et al⁴ present the results of a randomized controlled trial that investigated the effect of different HFNC flow rates on extubation outcomes. They included 169 patients admitted to 5 ICUs who received at least 2 days of invasive mechanical ventilation for acute hypoxemic respiratory failure. After extubation, the patients were assigned randomly to receive HFNC at 60 L/min vs 40 L/min for 24 hours, with Fio₂ titrated to target a peripheral arterial oxygen saturation of at least 92%.

The primary outcome, a composite of reintubation or use of noninvasive ventilation within 48 hours after extubation, occurred in 19 patients (22.1%) in the 40 L/min group and in 14 patients (16.9%) in the 60 L/min group (risk difference, 5.2%; 95% CI, –6.7% to 17.1%; P = .39). No difference in ICU and hospital mortality rates was found in the 2 groups (7 [8.1%] vs 3 [3.6%]; P = .21, and 7 [8.1%] vs 10 [12.1%]; P = .4). Based on these findings, the authors⁴ concluded that starting HFNC after extubation with a flow rate of 40 L/min, with as-needed up-titration, may be a reasonable strategy compared with routinely setting the flow at 60 L/min in all patients.

In our opinion, this is an important study that provides interesting insights into the association between flow setting during HFNC and relevant clinical outcomes. However, 3 important aspects must be highlighted. First, because of the relatively limited number of patients included, the study may not have been powered enough to exclude small differences between the 2 groups. Second, the lower flow (40 L/min) was associated with a higher risk of escalation in respiratory support, defined as the need of noninvasive ventilation or up-titration of HFNC settings (24 [27.9%] vs 8 [9.6%]; P = .002). Third, a preplanned subgroup analysis showed a potential benefit of the higher flow in patients with worse oxygenation before extubation.⁴ For all these reasons, the findings of this study should be considered as explorative and must be confirmed in further studies on larger population of patients.

In addition to the flow, it has been shown that temperature setting (in the present study, it was kept at 34 °C in all patients) also plays a relevant role, having a significant impact on patient comfort.⁵ Compared with noninvasive ventilation, HFNC seems to be characterized by better patient comfort, which might be 1 of the most important factors contributing to its efficacy.⁶ Indeed, improved comfort means more time on the device; improved comfort has also been shown to contribute, at least partly, to the reduction in minute ventilation observed with HFNC. Several studies have tried to assess the role of comfort in patients undergoing HFNC, despite the lack of scales specifically validated in patients supported with this technique.⁷ Therefore, it would have been interesting to include comfort among the secondary outcomes assessed in the population of patients included in this study. Moreover, temperature setting is important not only for comfort but also for physiologic reasons; indeed, for at least 24 hours of treatment, 40 L/min compared with 60 L/min can cause different nasal dryness, nasal humidity, and effects on mucociliary function for clearance of secretions and airway defense.^8,9 These aspects can significantly influence the clinical outcomes of patients in the postextubation period. Last but not least, as underlined by the authors,⁴ a difference in flow of 20 L/min has a significant impact on the amount of oxygen consumed, which is relevant for the environmental sustainability of the technique.

Considering the increasing use of HFNC, not only in patients who are critically ill and admitted to the ICU but also in general wards,¹⁰ further studies certainly are needed to better understand the optimal settings of HFNC in different categories of patients and in different phases of the disease. HFNC setting should aim toward the customization of patient’s treatment based on the assessment of clinical needs, supported by scientific evidence, and oriented to patient comfort.