In the present cross-over study, we show that, as compared to standard oxygen, HFOTTRACHEAL mitigates the negative swing in airway pressure during inspiration, and, when flow is set at 50 L/min, ameliorates oxygenation and slightly reduces respiratory rate. With similar flow rates, tracheal expiratory pressure is significantly lower with HFOTTRACHEAL than with HFOTNASAL, suggesting that the physiologic effects of HFOTTRACHEAL are milder than HFOTNASAL. A gas flow of 50 L/min should be set with the tracheal interface to slightly improve oxygenation and reduce respiratory rate.
Several studies addressed the effects of HFOTNASAL in a variety of clinical scenarii . Although high-flow oxygen can be delivered through tracheostomy, few data elucidate its mechanisms of action, which can be different from HFOTNASAL .
During HFOTTRACHEAL, PaO2/FiO2 ratio increases proportionally to gas flow. However, when compared to standard oxygen via heat and moisture exchangers, only 50 L/min generate improvement in PaO2/FiO2 ratio. These data are partially consistent with what has been reported for HFOTNASAL  and may be explained by the following mechanisms:
Increasing flow rate up to 50 L/min can limit air dilution of inhaled gas mixture, enabling more accurate delivery of set FiO2. This can be demonstrated by the reduction of the inspiratory airway pressure swing during HFOTTRACHEAL.
Increasing flow rate yields a concomitant increase in peak and mean expiratory pressure. Although the increase in tracheal pressure generated by HFOTTRACHEAL is lower than the one reported during HFOTNASAL [11, 14, 15, 28], this rise in expiratory pressure may still contribute to increase end-expiratory lung volume, reduce shunt fraction, optimize lung mechanics and improve oxygenation [11, 13, 18, 29].
One previous report showed that, when compared to T-Piece with a Venturi generator in tracheostomized patients, airway pressure and SpO2/FiO2 slightly increase during 50 L/min HFOTTRACHEAL . However, because of the entrainment effect, Venturi systems can provide flows up to 30–50 L/min and cannot be considered standard oxygen devices . Standard oxygen through heat and moisture exchangers represents a widely used alternative for oxygen therapy in tracheostomized patients.
We have shown that standard oxygen through heat and moisture exchangers produces positive expiratory pressure, which is comparable to the one obtained with 30 L/min of high-flow oxygen through an open system. In fact, oxygenation between these two settings was similar. For the same gas flow (≈ 10 L/min), oxygenation and tracheal expiratory pressure were higher with the standard oxygenation (closed system) than with the HFOTTRACHEAL device (open system). This suggests that the oxygenation changes are dependent on the amount of tracheal expiratory pressure. However, mechanisms of airway pressure generation may be different between the two devices: with standard oxygen, the increase in pressure depends on the expiratory resistance produced by the heat and moisture exchanger; while, during HFOTTRACHEAL, positive expiratory pressure is produced by patient’s expiration against the delivered gas flow in an open system and airway pressure is more stable over the respiratory cycle (i.e., less negative during inspiration). In this context, avoidance of excessive negative inspiratory swings in airway (and pleural) pressure is important to mitigate the risk of negative pressure pulmonary edema, whose occurrence induces lung damage and worsens oxygenation .
HFOTNASAL lowers inspiratory resistance and enhances anatomical dead space clearance with CO2 washout [32, 33], finally reducing work of breathing [11, 13, 27, 34]. Our study shows that 50 L/min HFOTTRACHEAL lowers respiratory rate without changes in PaCO2, as compared to standard oxygen. A reduction in respiratory rate has been reported during HFOTNASAL [5, 35] and has been linked to anatomical dead space clearance, increased tidal volume, diminished resistive work of breathing and, in chronic obstructive pulmonary disease patients, increased positive expiratory pressure [13, 33, 36].
Work of breathing reduction by HFOTNASAL is obtained at 30 L/min and is minimally enhanced by further increases in gas flow : differently, 50 L/min of HFOTTRACHEAL are needed to generate effects on respiratory rate. It is, therefore, reasonable to hypothesize that, in tracheostomized patients:
lower anatomical dead space and inspiratory resistance reduce the size effect of the intervention, that consequently requires higher flows to generate a significant effect;
inspired and expired flows are forcedly unidirectional, thus clearing anatomical dead space and improving breathing efficiency : this contributes to CO2 washout independently from the device used for oxygen therapy, thereby mitigating the effect of HFOTTRACHEAL.
Our results are consistent with recent data indicating that HFOTTRACHEAL minimally affects neuro-ventilatory coupling, work of breathing and gas exchange after weaning from mechanical ventilation .
Differences with HFOTNASAL
Our comparison of HFOTTRACHEAL and HFOTNASAL in the same patients represented a unique opportunity to highlight the contribution of upper airway resistance to positive-pressure generation during HFOTNASAL. In fact, to our knowledge, no other data clarify the behavior of lower airway pressure during this treatment. The average expiratory pressure reported in our study is similar to what has been reported for pharyngeal pressure [11, 15, 28]. However, tracheal pressure during HFOTNASAL was not constant over the respiratory cycle and became negative during inspiration in 4 of the 5 studied patients, which is different from what has been reported on upper airway pressure . Our results indicate that expiratory pressure in lower airways is higher and more inter-individually variable when high flows are delivered through nasal cannula than through tracheostomy. This suggests that the mechanism of expiratory pressure generation during high-flow oxygen is dependent not only on gas flow rate, but also on the greater resistance offered by upper airways and patient’s expiratory flow. In tracheostomized patients, resistance is limited, and the generated pressure is minimal. Patient’s expiratory flow has wide inter-individual variability according to the resistive and elastic properties of the respiratory system and to the eventual recruitment of expiratory muscles : thus, the pressure produced by HFOTNASAL is variable among subjects, also if respiratory rate with HFOTTRACHEAL is similar (Fig. 3) .
Our study shows that the effects of HFOTTRACHEAL are milder than HFOTNASAL, likely because the dedicated interface is completely open. HFOTTRACHEAL allows to limit the negative swing in inspiratory airway pressure, but both the dead space washout and the generation of positive expiratory pressure are limited. From a clinical perspective, our findings suggest that a minimum gas flow of 50 L/min should be set during HFOTTRACHEAL to slightly improve oxygenation and reduce respiratory rate, as compared to standard oxygen. Whether these mild physiologic effects are cost-effective and may clinically benefit the management of tracheostomized patients cannot be established from our data and should be addressed in further investigations.
First, we did not measure effectively delivered FiO2, as performed elsewhere . As a result, the calculation of PaO2/FiO2 ratio may be subject to errors, especially if lower flows are used . Nevertheless, our approach is clinically reproducible and we used a formula that has recently been shown to provide satisfactory correlation with actual FiO2 .
Second, we did not measure work of breathing by esophageal manometry . However, esophageal catheter insertion in awake and spontaneously breathing patients may be challenging and eventually require some sedation. Importantly, during HFOTNASAL, changes in respiratory rate have been shown to reflect variations of the work of breathing [13, 33].
Third, there was no wash-out period between the applied interventions during HFOTTRACHEAL. However, our approach is consistent with previous investigations on the topic , and the randomized order of the interventions should have mitigated any carry-over effect on the observed results. Accordingly, the main outcomes of the study were not affected by the sequence of applied flow settings.
Fourth, during HFOTNASAL, absence of major leaks through the stoma was assessed by hand. Unfortunately, we had no other way to assess if minimal leaks were present. We believe, however, that even minimal leaks, if present, should not have affected tracheal pressure measurement. In fact, the tracheal pressure values we report are similar to nasopharyngeal pressure values measured in non-tracheostomized patients by others [13,14,15].
Finally, we showed that expiratory pressure increase due to HFOTNASAL has wide inter-individual variability. Whether and to what extent expiratory flow limitation and expiratory muscles recruitment contribute to this is unknown and remains to be established in further investigations [38, 42].
HFOTTRACHEAL generates small flow-dependent improvement in oxygenation and increases in tracheal expiratory pressure. When compared to standard oxygen, a minimum flow of 50 L/min is needed during HFOTTRACHEAL to improve oxygenation, increase expiratory pressure, limit inspiratory airway pressure swings and reduce respiratory rate. At same gas flow, HFOTNASAL produces higher expiratory pressure than HFOTTRACHEAL.