Superiority of OxyMaskTM with less carbon dioxide rebreathing in children

Despite the growing importance of oxygen-delivery devices worldwide, there are only a few reports of physiological data on various oxygen masks in children. The possibility of carbon dioxide (CO2) rebreathing has been a prevalent concern with the use of oxygen-delivery devices. OxyMask KidTM (Southmedic Inc. Canada; hereafter OxyMask) is expected to reduce CO2 rebreathing even at low oxygen flow rates because of its structural features. Biological data using OxyMask in children have not been well investigated. Measured respiratory parameters of OxyMask with those of a simple oxygen mask in healthy children were compared. Ten subjects were enrolled, with a median age of 5.4 years. All subjects used both OxyMask and a simple oxygen mask. The fraction of inspiratory oxygen (FIO2), partial pressure of inspiratory CO2 (PICO2), and partial pressure of end-tidal CO2 were measured using a sidestream gas-sampling monitor in all subjects. The oxygen flow rate was set at 1, 3, 5, and 10 L/min. FIO2 levels were higher with OxyMask than those with the simple oxygen mask at 3 L/min of oxygen. PICO2 levels were significantly lower with OxyMask than those with the simple oxygen mask (1.5 mmHg vs. 3.7 mmHg at 1 L/min, P = 0.005; 1.0 mmHg vs. 2.7 mmHg at 3 L/min, P = 0.005, respectively), whereas PICO2 levels were higher at low oxygen flow rates with both masks. Conclusion: Our results showed that higher FIO2 and less CO2 rebreathing were achieved with OxyMask than those with a simple oxygen mask at low flow rates of oxygen in healthy children. What is Known: • OxyMask is expected to reduce carbon dioxide rebreathing even at low oxygen flow rates because of its structural features. • Efficacy has been demonstrated in experimental models and adult data, but clinical data on the use of the OxyMask in children are limited. What is New: • Higher fraction of inspiratory oxygen and lesser carbon dioxide rebreathing were achieved with OxyMask than with a simple oxygen mask at low flow rates of oxygen in healthy children What is Known: • OxyMask is expected to reduce carbon dioxide rebreathing even at low oxygen flow rates because of its structural features. • Efficacy has been demonstrated in experimental models and adult data, but clinical data on the use of the OxyMask in children are limited. What is New: • Higher fraction of inspiratory oxygen and lesser carbon dioxide rebreathing were achieved with OxyMask than with a simple oxygen mask at low flow rates of oxygen in healthy children


Introduction
Administration of oxygen is a first-line therapy for the treatment of respiratory failure. Because the impact of respiratory infections in children is significant, classical treatment of oxygen therapeutic strategies remains important worldwide [1]. Various oxygendelivery devices are available for children. High-concentration oxygen is required for children with severe respiratory failure [2]. However, potential adverse effects of unnecessary highconcentration oxygen have also been reported [3].
Furthermore, the possibility of carbon dioxide (CO 2 ) rebreathing has been pointed out with the so-called low-flow oxygen-delivery devices such as simple oxygen masks [4]. Physiologically, children are less tolerant to hypoxia than adults owing to a higher oxygen consumption and smaller functional residual capacity. Moreover, children are more prone to respiratory muscle fatigue due to inefficient respiratory muscles and high airway resistance from smaller airways. Therefore, it is essential to understand the characteristics of oxygen-delivery devices in children, such as inspired oxygen concentration and washout of CO 2 at various oxygen flow rates. The OxyMask Kid TM (Southmedic Inc. Canada; OxyMask) is a relatively new oxygen-delivery device, developed in the 2000s, with a unique structure that can provide highconcentration oxygen by using a diffuser technology in its inlet, which forms air vortexes that minimize oxygen dilution. Moreover, the unique open-style design of OxyMask reduces CO 2 rebreathing even with a low oxygen flow rate [5,6]. Although some adult data showing the effectiveness of OxyMask are available, clinical data on the use of the OxyMask in children are limited. Thus, we compared the measured inspired oxygen concentrations and CO 2 rebreathing levels in children using OxyMask with those of a conventional simple oxygen mask at various oxygen flow rates.

Materials and methods
This study was a prospective open-label crossover study of healthy child volunteers. Written informed consent was obtained from the parents of each participant. Ten children aged 1-10 years were recruited between April 2014 and March 2015. OxyMask TM Kid and a conventional simple oxygen mask (Japan Medical Next, Japan) were used in all subjects ( Fig. 1). All subjects used a pediatric size. This study was conducted with the approval of the ethics committee of our hospital (ethics approval number rin2014-27).
The data were collected with the subjects seated in an upright position during the measurement procedure. Baseline values were established when the subjects were not wearing the masks, and measurement was started 90 s after they started receiving supplemental oxygen under each condition (oxygen flow rate of 1, 3, 5, and 10 L/min). One-hundred percent oxygen from wall oxygen supply was used for all experiments (without the use of a blender). No washout time was provided for the next condition onward. A sidestream respiratory gas monitor (DS-7300; Fukuda Denshi, Japan) was used, and a sampling tube was inserted into the nasal cavity. Respiratory rate, the fraction of inspiratory oxygen (F I O 2 ), partial pressure of inspiratory CO 2 (P I CO 2 ), and partial pressure of end-tidal CO 2 (P ET CO 2 ) were obtained three times, every 30 s, and the average was taken under each condition. The order of each condition was not randomized. The OxyMask was used first, followed by a simple oxygen mask.
For comparisons between the two types of masks, the Wilcoxon signed-rank test was used for count and continuous variables. For comparison between each oxygen flow rate, the Friedman test and Wilcoxon signed-rank test with Bonferroni correction were performed. A two-sided P-value of <0.05 was considered statistically significant. Statistical analysis was performed using SPSS software (IBM SPSS Statistics, Version 21.0. IBM Corp., Armonk, NY).

Results
Ten subjects, three boys and seven girls, completed the study. The median age was 5.4 years (range, 1-10 years), and the median weight was 19.9 kg (range, 12-34 kg). The F I O 2 , P I CO 2 , and P ET CO 2 levels and respiratory rates were compared between OxyMask and a simple oxygen mask. As expected, the F I O 2 levels were increased by oxygen supplementation in a dose-dependent manner in both groups (Fig. 2a). F I O 2 levels tended to be higher in the OxyMask group than in the simple oxygen mask group and were significantly higher at an oxygen flow rate of 3 L/min (P = 0.028, Fig. 2b). P I CO 2 levels were increased with OxyMask at an oxygen flow rate of 1 L/min (P = 0.03) and with the simple oxygen mask at rates of 1 and 3 L/ min (P = 0.02, P = 0.02). P I CO 2 was significantly lower with OxyMask than with the simple oxygen mask at oxygen flow rates of 1 and 3 L/min (OxyMask vs. simple oxygen mask (median); 1.5 mmHg vs. 3.7 mmHg at 1 L/min (P = 0.005), 1.0 mmHg vs. 2.7 mmHg at 3 L/min (P = 0.005), respectively, Fig. 2b). P I CO 2 was also lower in the OxyMask group at an oxygen flow rate of 5 L/min, but the difference was not significant (Fig. 2b). P ET CO 2 was significantly higher with a simple oxygen mask than with an OxyMask at an oxygen flow rate of 1 L/min (P = .032), but a consistent pattern was not identified (Fig. 2c). There was no significant difference in respiratory rates between the groups (Fig. 2d).

Discussion
Here, we reported differential characteristics between OxyMask and a simple oxygen mask in children. Our results showed that OxyMask provided a higher concentration of oxygen with lower inspiratory CO 2 than a simple oxygen mask, which suggests superior gas exchange efficiency of OxyMask relative to that of the simple oxygen mask.
Administration of high oxygen concentrations is an important function of oxygen-delivery devices. In critically ill children, prompt administration of high-concentration oxygen is essential in the acute phase of treatment [2]. This study showed that the maximum inhaled oxygen concentration was higher in OxyMask than in the simple oxygen mask. According to data from healthy adult volunteers using an OxyMask, the F I O 2 values were approximately 0.4, 0.6, 0.75, and 0.8 at oxygen doses of 3, 5, 10, and 15 L/min, respectively. Their results were slightly higher than those in our study [5]. This gap may be owing to a difference in sampling site, mask construction, or improper mask fitting in children. Previous simulation studies have shown that mask fitting and the respiratory rate significantly affected F I O 2 levels [7,8]. Our data are clinically valuable because of the scarcity of actual measurements of F I O 2 in children. These data may be a clue to predict appropriate concentrations of oxygen with an expected F I O 2 .
The issue of rebreathing with low-flow oxygen-delivery devices has been described in previous reports [4]. In adult cases, a simple oxygen mask increased the minute ventilation up to 140% by increasing the tidal volume due to rebreathing at an oxygen flow rate of 3 L/min [4]. In fact, rebreathing of CO 2 was observed with the simple oxygen mask up to 3 L/min of oxygen flow in this study. The simple oxygen mask is widely used in children with respiratory failure. However, the use of a simple oxygen mask in children with ventilation disturbance can lead to CO 2 rebreathing and increased respiratory workload. In contrast, OxyMask has an advantage over other masks because of less rebreathing, especially with low oxygen flow rates. The results of this investigation suggest that OxyMask and simple oxygen masks should be used at flow rates ≥ 3 or 5 L/min, respectively, to prevent rebreathing.
Although high-flow oxygen devices, such as a high-flow nasal cannula, venturi masks, or non-rebreathing masks, are reportedly more effective than a simple facial mask [9,10], Fig. 1 The picture on the left shows an OxyMask, with a large open area and an internal diffuser structure. The picture on the right shows a simple oxygen mask introducing expensive oxygen-delivery devices and high rates of oxygen consumption may be a significant burden for developing countries [1,11]. In the adult study, OxyMask achieved the same level of F I O 2 at lower oxygen flow rates than those of the venturi mask [12]. This suggests the possibility of reducing oxygen consumption throughout the hospital. Although OxyMask is more expensive than a simple oxygen mask, OxyMask may cover a wide range of F I O 2 levels without rebreathing even at low oxygen flow rates. We have carried out additional experiments at higher oxygen flow rates comparing the performance of the OxyMask and the nonrebreathing mask (Supplemental Fig. 1). The data showed the non-rebreathing mask provided higher F I O 2 than the OxyMask, but the OxyMask performed reasonably well and there was still an advantage of the OxyMask in terms of CO 2 rebreathing (Supplemental Fig. 2). Further studies are warranted to demonstrate this by comparing it with other oxygen devices. Recently, oxygen toxicity with excessive concentrations of oxygen supply has been reported, and it is recommended that the oxygen dose should be appropriately reduced in children [2,3]. Because a simple oxygen mask could not reduce FiO2 without causing rebreathing issues, a nasal cannula or other alternative devices would be necessary to achieve appropriate oxygen therapy.
There were several limitations to this study. First, the data were obtained only from healthy children. Thus, it is unclear whether the results can be applied to sick children, such as those with respiratory failure. Because children with respiratory distress usually have more respiratory workload and CO 2 retention, rebreathing of CO 2 might be more problematic. Second, mask fitting can be an issue. Face masks are designed to be closely fit to the contours of a face. Performance reportedly can considerably depend on how well a mask is fit to an individual [8]. In this study, measurements were performed after natural mask fitting by the children themselves, allowing air leakage from the mask perimeter. Third, the small sample signed-rank test. The black lines are the median; above and below the boxes are the interquartile range (IQR); the whiskers are the maximum and minimum values up to 1.5 times the IQR; and the dots are the outliers size of this study may be underlying the observed relatively large sampling variability. Therefore, further evaluation is required to confirm our findings in a larger sample size.
In conclusion, OxyMask achieved significantly higher F I O 2 with less CO 2 rebreathing at a flow rate of 3 L/min of oxygen than those with a simple oxygen mask in healthy children.
Abbreviations F I O 2 , Fraction of inspiratory oxygen; P ET CO 2 , Partial pressure of end-tidal carbon dioxide; P I CO 2 , Partial pressure of inspiratory carbon dioxide Supplementary Information The online version contains supplementary material available at https://doi.org/10.1007/s00431-021-04157-1.
Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on request.

Code availability N/A
Authors' contributions S. Ogiwara was the principal author of the study and contributed to the design of the study; performed the experiments, clinical data collection and analysis; and drafted the first version of the manuscript. T. Tamura performed the experiments and drafted the first version of the manuscript. S. Sai performed data analysis and drafted the first version of the manuscript. M. Nojima performed data analysis and drafted the first version of the manuscript. S Kawana contributed to the design of the study and drafted the first version of the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Declarations
Ethics approval The study was conducted with the approval of the ethics committee of our hospital (ethics approval number rin2014-27).
Consent to participate Written informed consent was obtained from all individual parents. All the methods were conducted following the relevant guidelines, regulations, and the Declaration of Helsinki.
Consent for publication Written informed consent was obtained from all individual parents included in the study.

Competing interests
The authors declare no competing interests.