Validation of Novel Completely Sealed Nasal Positive Airway Pressure Device: SuperNO2VA™ EtCO2 Measurement and Pressure Test Performance

Background: SuperNO2VA™ Et Nasal Mask (Vyaire Medical, Inc., United States) is a new nasal mask with an integrated sampling hood to capture exhaled gases and enable accurate measurements of end tidal carbon dioxide (EtCO2). The authors hypothesized that the SuperNO2VA Et design would measure EtCO2 more accurately than a predicate EtCO2 sampling line, the Smart CapnoLine® Plus, Adult/Intermediate CO2 Oral-Nasal Set (Medtronic, United States). Methods: A simulated patient setup enabled comparison of the accuracy of CO2 measurements within the SuperNO2VA Et and a predicate device for eight condition combinations of input CO2; breath rate and tidal volume (VT); and O2 flow rates. These tests were repeated with simulating Nasal Breathing and Oral Breathing. Results: Testing demonstrated that measurements of 1% and 5% input CO2 within the SuperNO2VA Et were accurate for a range of respiratory rates, VT, O2 flows, and CO2 concentrations. CO2 measurement errors were significantly larger for the Oral-Nasal Set compared to the SuperNO2VA Et for both 1% Input CO2 (-0.12%vol vs. -0.01%vol, p = 0.0005) and 5% Input CO2 (-0.93%vol vs. -0.08%vol, p 0.0001). At 5% Input CO2, eight of the 12 trials for the Oral-Nasal Set failed to meet the ISO accuracy specification, while all SuperNO2VA Et measurements met the specification. The accuracy of CO2 measurement within the SuperNO2VA were not different for Oral and Nasal Breathing trials for both CO2 concentration (1%: p = 0.33, 5%: p = 0.064). With the Oral-Nasal Set, CO2 measurements were lower during Oral compared to Nasal Breathing (1%: p = 0.0005, 5%: p = 0.0091). Conclusions: Based on performance outcomes, use of the SuperNO2VA Et offers significantly more accurate measurement of EtCO2 than the predicate EtCO2 sampling line. Measurements of EtCO2 within the SuperNO2VA Et are accurate over a range of CO2, breathing rates, tidal volumes, and O2 flows, as well as for nasal and oral breathing.


Introduction
Moderate and deep sedation have long been associated with high rates of respiratory complications such as hypoxemia and hypoventilation [1] [2] [3]. These complications arise from sedation medications and inadequate monitoring that contribute to or cause upper airway obstruction (UAO), central respiratory depression, or both [1] [2] [3]. Ventilation monitoring and supplemental oxygenation can mitigate respiratory complications in both sedation settings.

Monitoring
Traditionally, pulse oximetry had enabled limited and indirect respiratory monitoring. Because such devices measure only peripheral oxygen saturation, their use created the potential for delaying complication detection, with possible subsequent health risks for the patient. For example, pulse oximetry is unable to directly detect hypoventilation or apnea, especially in patients undergoing procedural sedation while receiving supplemental oxygen [4] [5].
A superior monitoring approach involves the breath-to-breath measurement of the concentration of carbon dioxide (CO 2 ) in exhaled respiratory gas, which has gained ready acceptance, particularly with endorsement from the American Society of Anesthesiologists (ASA) for use of end-tidal capnography (EtCO 2 ) as a standard of care for moderate and deep procedural sedation [6] [7].
Although capnography has greater efficiency than pulse oximetry for effective detection of hypoventilation and apnea, accurate and consistent measurements of the EtCO 2 during minimally invasive procedures under deep sedation have historically been challenging [8]. This difficulty results from the capnography port of the nasal cannula being open to air, causing atmospheric gases to be entrained and sampled [9]. Additionally, delivery of supplemental oxygen to patients, particularly at flows >5 liters per minute (L/min), causes a "wash-out" or dilution of the sample of exhaled CO 2 and results in either a falsely low reading or no reading at all [10].

Supplemental Oxygenation
Recent prospective randomized controlled trials (RCTs) report up to 54% of all patients experience severe hypoxemia secondary to sedation-related UAO and respiratory depression [11]. Although passive oxygenating devices can provide Open Journal of Anesthesiology higher concentrations of oxygen, they are incapable of generating positive pressure to maintain airway patency. Continuous Positive Airway Pressure (CPAP) equipment has been shown to relieve UAO by creating a pneumatic stent [12].
However, their utility is limited by the machine's very large size and relatively greater expense, and the high oxygen flows required to maintain pressure also dilute EtCO 2 sampling [13] [14].
A recent RCT comparing the SuperNO 2 VA TM nasal PAP ventilation device (Vyaire Medical, Inc., United States) vs. nasal cannula with capnography during deep sedation documented a significantly higher minute ventilation and reduction in the incidence of severe hypoxemia in the SuperNO 2 VA TM nasal PAP ventilation device cohort compared to the nasal cannula with capnography cohort [15]. However, the design of the SuperNO 2 VA nasal PAP ventilation device had the disadvantage of being unable to capture EtCO 2 , especially in patients who exhale from their mouths, which also results in false apnea alarms.  The objectives of this study were to validate the capability of the Super-NO 2 VA TM Et to capture EtCO 2 exhaled from the nose and the mouth, provide 20 cm H 2 O positive pressure, quantify leak rates, and summarize the performance testing compared to a predicate device. States). This device is suitable for humans up to 50 kg (110 lb) and enables an adjustable VT from 30 to 700 milliliters (ml) per stroke and an adjustable respiratory rate from 7 to 50 breaths per minute (BPM). The concentration of CO 2 flowing through the surrogate nose and mouth was set using a digitally controlled flow meter and CO 2 source, and verified using a CO 2 monitor (Dräger Narkomed 6400). A Datex-Ohmeda 5250 Respiratory Gas Anesthesia Monitor (General Electric Healthcare, United States) connected to the EtCO 2 sampling port was used to monitor CO 2 . Testing assessed eight combinations of Input CO 2 (1% ± 0.25%; 5% ± 0.5%); breath rate and VT (12 BPM/500 ml; 20 BPM/300 ml); and O 2 flow rates (1 L/min; 5 L/min). Table 1 lists the combinations of Input CO 2 , Breath Rate/VT, and O 2 Flows that were tested. After a 3-min stabilization period to reach steady-state, the CO 2 waveform of the sensor connected to the EtCO 2 sampling port was recorded for 16 seconds via an analog port of an oscilloscope (Tektronix TBS2000, United States).

Statistical Analysis
Absolute and relative errors between the CO 2 Max, defined as maximum CO 2 during the 16-second trial, and the Input CO 2 were quantified for each DUT.

Effect of Supplemental Oxygen Flow Rate
To

Nasal Breathing vs. Oral Breathing
The same set of eight tests were repeated while simulating Nasal Breathing and Oral Breathing for each of the two devices (See Figure 4). For the Oral-Nasal Set, CO 2 Max measurements were significantly lower for the Oral Breathing compared to Nasal Breathing trials for Input CO 2 concentrations of 1% (paired t-test, p = 0.0005) and 5% (p = 0.0091). For the SuperNO 2 VA Et, there was no Figure 2. CO 2 Max Error (in %vol) for the eight condition performance tests for Oral-Nasal Set (orange) and SuperNO 2 VA Et Nasal Mask (blue). Horizontal shaded green areas correspond to the ISO 80601-2-55:2018 error limit (0.51% and 0.83% for 1% and 5% input CO 2 respectively). Filled circles are individual trials and bars represent mean error across the three trials for each condition test. and SuperNO 2 VA Et (blue) are compared to known Input CO 2 concentrations of 1% or 5% (horizontal dashed black lines). Shaded green areas correspond to the ISO 80601-2-55:2018 error limit (0.51% and 0.83% for 1% and 5% Input CO 2 , respectively). Bars are the average measurements across all trials performed under those conditions and error bars are the standard deviation of measurements across these trials. Figure 4. Comparison of maximum CO 2 measurements (i.e., CO 2 Max) measurements during Nasal Breathing and Oral Breathing trials. CO 2 Max with Oral-Nasal Set (orange) and SuperNO 2 VA Et (blue) are compared to known Input CO 2 concentrations of 1% or 5% (horizontal dashed black lines). Shaded green areas correspond to the ISO 80601-2-55:2018 error limit (0.51% and 0.83% for 1% and 5% Input CO 2 , respectively). Bars are the average measurements across all trials performed under each condition and error bars are the standard deviation of measurements across these trials. Open Journal of Anesthesiology significant difference in CO 2 Max measurements for Nasal Breathing and Oral Breathing trials for both Input CO 2 concentrations (1%: p = 0.33, 5%: p = 0.064).
At an Input CO 2 of 5%, the Oral-Nasal Set had 10 out of the 12 Nasal Breathing trials and 9 out of 12 Oral Breathing trials outside of the ISO error bound (shaded green region).

Flow Leak Rate
Both the SuperNO 2 VA Et Nasal Mask and the full-face anesthesia mask successfully held a pressure of 20 cm H 2 O for three, 5-minute trials. The SuperNO 2 VA Et Nasal Mask had a leak rate of 2.0 L/min for all three samples compared to the mean leak rate of 2.7 (range: 2.5 -3.0 L/min) for the anesthesia mask ( Table 2).

Discussion
This performance test study compared the functionality of the SuperNO 2 VA Et Nasal Mask and Oral-Nasal capnography in eight condition combinations with binary variations of input CO 2 ; respiratory rate and VT; and O 2 flow rates. Our results indicate that SuperNO 2 VA Et Nasal Mask provided significantly greater accuracy in measuring EtCO 2 across a range of typical respiratory rates, tidal volume, O 2 flow, and CO 2 concentration, well within the error bounds specified by ISO (Figure 2). The error of CO 2 measurements within the SuperNO 2 VA Et mask was less than 0.1%vol at both 1% and 5% CO 2 concentrations. In contrast, measurements from the Oral-Nasal Set did not meet the ISO standard for eight out of the twelve trials at a physiological CO 2 level of 5% (i.e., 38 mmHg) and underestimated CO 2 by −0.93%vol (−18.6%). Clinically, this dramatic underestimation of CO 2 could result in false positives of hypocapnia or apnea or missing true hypercapnic events.
Capnography has become standard-of-care during moderate and deep sedation in order to provide real-time feedback of the patient's respiratory status and early detection of respiratory depression [6] [7] [17]. With good quality CO 2 sampling, capnography has been shown to significantly reduce adverse events, such as apnea and desaturation, during moderate and deep sedation [18] [19] [20]. However, EtCO 2 measurements using nasal cannula sampling are often not accurate during minimally invasive procedures under deep sedation [8]. The inaccuracy of EtCO 2 using nasal cannulas arises because they are exposed to  [21]. Both of these effects result in an underestimation in CO 2 measurements.
The SuperNO 2 VA Et offers a solution to this CO 2 sampling problem by capturing all expired gases from the patient's mouth and nose using an integrated flexible sampling hood over the patient's mouth. The SuperNO 2 VA Et also provides positive pressure to maintain upper airway patency. Use of the Super-NO 2 VA results in increased minute ventilation and a reduction in severe hypoxemia compared to a nasal cannula [15]. Furthermore, in contrast to traditional anesthesia masks, the SuperNO 2 VA Et does not cover the full face and therefore allows the clinician access to the oral cavity during a procedure while delivering air, oxygen, or anesthesia gases and simultaneously sampling expired gases.
Delivery of supplemental oxygen using traditional nasal cannulas results in an underestimation of CO 2 [10] and the error increases with the flow rate as more of the sampled gas is washed out with O 2 when using traditional nasal cannulas [21]. In this study, we saw no decrease in accuracy of CO 2 measurements when using the SuperNO 2 VA Et ( Figure 3). There was also no significant difference between 1 and 5 L/min O 2 flow rates using the Oral-Nasal Set. However, this dilution effect is typically observed for nasal cannulas at flow rates greater than 5 L/min which were not tested in this study.
Another source of capnography error arises when the patient breathes orally, which is common during respiratory distress and sedation, especially in obese patients with obstructive sleep apnea (OSA) [10]. For example, in non-intubated volunteers, mouth breathing resulted in a 2 mmHg decrease in EtCO 2 compared to nasal breathing [22]. In the present study, the accuracy of the CO 2 measurements within the SuperNO 2 VA Et was similar for Nasal and Oral Breathing ( Figure 4). The Nasal-Oral Set used in this study was engineered with an oral scoop intended to obtain gas samples from the mouth as well as the nose. Despite this design, CO 2 measurements were significantly lower during Oral Breathing compared to Nasal Breathing when using the Oral-Nasal Set.
Furthermore, the SuperNO 2 VA Et Nasal Mask maintained a positive pressure of 20 cm H 2 O within the mask with a low leak rate of 2.0 L/min, demonstrating superior fit to a full-face anesthesia mask. The majority of the leak from the Su-perNO 2 VA Et masks comes from the EtCO 2 sampling port. In order to achieve a sufficient seal for the full-face anesthesia mask, the balloon had to deflated and inflated in order to achieve a maximum seal.
The SuperNO 2 VA Et Nasal mask is a sealed system around the nose that keeps all expired CO 2 within the system, preventing atmospheric dilution. The larger hood over the mouth increases capture of exhaled CO 2 from mouth. The size of the SuperNO 2 VA Et nasal and oral apertures for EtCO 2 capture was designed based on fluid dynamic calculations to allow for an equal amount of capture.

Limitations
This study was conducted to determine specific performance features of the Su-Open Journal of Anesthesiology perNO 2 VA Et Nasal Mask in a controlled setting using a face surrogate. The study results document the significantly better accuracy of the device and its potential to aid in providing optimal patient care during sedation. Future clinical work should be conducted to confirm if the use of the SuperNO 2 VA Et improves clinical outcomes and decreases adverse events in patients under sedation.

Conclusions
The testing described in this report demonstrated that measurements of CO 2 within the SuperNO 2 VA Et Nasal Mask are accurate for a range of respiratory rates, tidal volumes, O 2 flows, and CO 2 concentrations and meet ISO standards.
The design of the SuperNO 2 VA Et Nasal Mask allows for a good seal against a patient's face to maintain positive pressure with minimal leak.
This performance and the positive pressure mechanism of the SuperNO 2 VA Et Nasal mask to improve upper airway obstruction without sacrificing end-tidal measurements differentiate the device favorably from other methods of airway management. Additionally, its design and function improved airway management comparatively to passive devices that, because they cannot provide positive pressure to force airways open, lack the ability to maintain airway patency.
In practice, the performance of SuperNO 2 VA Et Nasal Mask may help prevent patients from becoming hypoxemic and improve their overall outcomes in the settings of moderate or moderate and deep sedation.