To the best of our knowledge, this is the first randomized controlled trial using HFNC in advanced cancer patients. In this study, we found that HFNC can enhance patients comfort, which is reflected in the decrease of VAS score, dryness of mouth score, and SRSS score. The beneficial effects of HFNC in several objective parameters, such as RR, HR, SpO2, PaO2, PaCO2 were also showed.
There are several explanations for the decrement of dyspnea. First, HFNC can increase expiratory resistance of the nose because of the different sizes of the cannula and the jet-flow effect against exhaled gas 24. The expiratory pressure will further prolong the duration of exhalation, so decreasing respiratory rate. The slower and deeper breathing can decrease the work of breathing25–27 and increase tidal volume24, which can decrease the proportion of dead-space volume and then improve breathing efficiency24. Thus, patients can breathe more comfortably with less dyspnea. Compared with HFNC, the conventional nasal catheter oxygen inhalation provides oxygen at flow rates <15 L/min28–30. It lacks the ability to wash out the nasopharyngeal dead space and decrease work of breathing. Secondly, HFNC can decrease anatomical dead space in the upper airway, which is attributed to the high flow effect14, 24. Nasopharyngeal dead space washout can reduce rebreathing of expired air and CO2, create a fresh oxygen reservoir within the upper airways31, 32, thus improving breathing efficiency and reducing tachypnea24, 33–35. Thirdly, the high flow of delivered gas which exceed the patient’s demand can help overcome resistance during inspiratory period36. Meanwhile, the inspiratory air-flow dynamics is improved with HFNC, as evidenced by the fact that the pressure remained above atmosphere for most of the inspiratory phase24. This increase would help subjects overcome resistance and raise the driving pressure for inspiration, thus decrease work of breathing and dyspnea. Fourthly, HFNC therapy delivers a low level of positive airway pressure in expiratory phase37–39 which contributes to lung compliance increment, alveoli recruitment and end-expiratory lung volume increment40. Thus, the oxygenation was improved and the dyspnea was lessened. Lack of humidification, secretions in the airways, such as sputum, become thicker and harder to expel, making it more likely that subjects with advanced cancer will experience dyspnea41. As is shown before, HFNC plays a vital role in heating inspired gas close to body temperature level (37°C) and humidifying the respiratory system to saturation, especially in high flow rates, where conventional nasal catheter oxygen inhalation fail 36, 42. The mucociliary function and secretion elimination is facilitated43. Furthermore, the required metabolic cost of warming and humidifying of inspired gas is reduced, especially in subjects whose RR are increased with advanced cancer33. Thus, another reasonable explanation is the fully and effectively humidification of HFNC, which can help subjects clear airway more easily and relieve dyspnea. Owing to mechanism mentioned above, the effect of HFNC on dyspnea was better than that of conventional nasal catheter oxygen inhalation among patients with advanced cancer.
Dryness of the mouth can be caused by breathing dry or insufficiently humidified oxygen44, which may frequently result in discomfort. AARC Clinical Practice Guideline suggested that the humidification provided by the nasal mucosa becomes insufficient when administered at flow rates exceeding 4 L/min11. The consist of an active heated humidifier of HFNC system allows patients to be administered fully humidified high-flow oxygen13, thus the HFNC system reduced discomfort related to symptoms of mouth dryness in patients with advanced cancer. Several investigators have reported that improving the humidification of the inspired gas ameliorates patient comfort, which is congruent with our study44.
Owing to the less dyspnea and dryness of the mouth by using HFNC, sleep quality was significantly improved in the experimental group after intranasal high-flow oxygen inhalation, while there was no significant change in control group.
HR and RR were chosen to reflect the degree of improvement of vital signs before and after treatment. As is mentioned above, the high flow of HFNC can flush out the dead space in upper airway ,improve gas exchange and lung volume, enhance the breath efficiency and increase tidal volume, thus HNFC exert various effects in the respiratory system, especially lower respiratory rate and effort18. We speculate that owing to the comfort of patients which is attributed to lower work of breath and less dyspnea, HFNC can reduce anxiety in patients. Thus, with less anxiety, the patients are calmer, which helps the heart rate decreased.
Based on the observation about persistent improvement of SpO2 measured by pulse oximetry, we can conclude that HFNC is associated with greater overall oxygenation17. First, the conventional nasal catheter oxygen inhalation provides oxygen at flow rates that are lower than patients’ inspiratory demands. As a result, the room air is entrained and administered oxygen is diluted36. The final concentration of oxygen truly delivered to the patient can be lower than the set FIO2 initially(FIO2SET). On the contrary, the HFNC which has the ability of generating high flow rates up to 60L/min that can even exceed the patient’s demand provides oxygen whose final concentration is tantamount to the FIO2 set initially13. Secondly, High flow rates with HFNC can create of a great oxygen reservoir in nasopharyngeal area and increase tidal volume31, 32. Thus, the oxygenation was greater in intervention group. Thirdly, there is an analysis demonstrating that higher pressures are obtained during expiration than inspiration, which are flow dependent40. It delivers a low level of positive airway pressure in expiratory phase37 which transmits to the alveoli, contributing to lung compliance increment and end-expiratory lung volume increment40. Also, we found that with the prolongation of time, the improvement of blood oxygen saturation was greater. It is possible that the airway pressures initially are low and thus a longer time period is needed to recruit any atelectatic lung areas45. HFNC may cause a reduction in PaCO2, which has been confirmed in both stable and acute COPD26. This is attributed to the wash-out of CO2 in the upper airway and increment of tidal volume.
This study has some important limitations. First, the sample size was small and only a 72-hour clinical intervention was conducted. The long-term effect of HFNC needs to be further studied. Second, there are many subjective outcome measures, and more objective indicators are needed to verify the effect of HFNC. Third, patients and research personals could not be blinded to group assignment. However, the person who performed the statistical analysis were blinded.
This study demonstrated that HFNC is a kind of promising oxygen therapy in advanced cancer patients with dyspnea undergoing palliative treatment. HFNC can significantly improve the symptoms of dyspnea, dryness of mouth and sleep quality among patients with advanced cancer. Moreover, HFNC can effectively decrease RR, HR and PaCO2, while increase SpO2 and PaO2. Consequently, HFNC can be a useful respiratory support strategy in supporting advanced cancer patients to feel more comfortable.