Exhaled Carbon Dioxide Monitoring Using Instantaneous CO2 Mode During High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants

Exhaled Carbon Dioxide Monitoring Using Instantaneous CO2 Mode During High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL Pediatric Pulmonology This is a preprint and has not been peer reviewed. Data may be preliminary. 20 May 2025 V1 Latest version Share on Exhaled Carbon Dioxide Monitoring Using Instantaneous CO2 Mode During High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants Authors : Yusuke Nakazawa , Kazuto Ueda 0000-0003-3297-024X , Yoshihiro Tanahashi , Toshiki Aoki , and YOSHIAKI SATO 0000-0001-6320-9176 [email protected] Authors Info & Affiliations https://doi.org/10.22541/au.174773523.32944775/v1 Published Pediatric Pulmonology Version of record Peer review timeline 572 views 163 downloads Contents Abstract Abstract Keywords Introduction Subjects and methods INST COMX Results Correlation between PCO and INST CO MX (3 min) and INST CO MX (5 min) Degree of coincidence Factors influencing DOC Discussion Conclusion Acknowledgments Competing Interests Author Contributions Figures Supplementary Material References Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: High-frequency oscillatory ventilation (HFOV) presents challenges for non-invasive CO 2 monitoring due to its rapid oscillations. This study examines the feasibility of instantaneous CO 2 partial pressure (INST CO 2 ) monitoring during HFOV with a capnometer equipped with a mainstream CO 2 sensor. Methods: This study included seven neonates receiving HFOV in the neonatal intensive care unit (NICU) at Shizuoka Children’s Hospital. INST CO 2 values were recorded over 3- and 5-min intervals surrounding each blood gas sampling to determine the maximum INST CO 2 value (INST CO 2 MX). The primary outcome was the correlation between INST CO 2 MX and arterial partial pressure of carbon dioxide (PCO 2 ). Results: A total of 216 paired INST CO 2 MX and PCO 2 values were analyzed. The coefficient of determination ( R 2 ) was 0.571 for INST CO 2 MX (3 min) and 0.579 for INST CO 2 MX (5 min). Univariable and multivariable analyses revealed that a lower fraction of inspired oxygen (FiO 2 ), reduced minute ventilation, and increased postnatal age were associated with improved concordance between INST CO 2 MX and PCO 2 . Conclusion: INST CO 2 MX demonstrated a strong correlation with PCO 2 in neonates undergoing HFOV. This novel, non-invasive monitoring approach may serve as a valuable tool for neonatal respiratory management. Future research is needed to validate these findings in broader patient populations and across various ventilatory settings. Exhaled Carbon Dioxide Monitoring Using Instantaneous CO 2 Mode During High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants Running Title: Instantaneous CO 2 Mode in High-Frequency Oscillatory Ventilation for VLBWI Infants Yusuke Nakazawa 1 , Kazuto Ueda 2 , Yoshihiro Tanahashi 3 , Toshiki Aoki 1 , Yoshiaki Sato 2 1 Pediatrics, Nakazawa Kodomo Clinic, Japan 2 Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, Nagoya, Japan 3 Department of Pediatrics, Toyota Memorial Hospital, Japan * Correspondence Yoshiaki Sato, MD, PhD, Division of Neonatology, Center for Maternal-Neonatal Care, Nagoya University Hospital, 65 Tsurumai-cho Showa-ku, Nagoya 466-8560, Japan. Tel: +81-(0)52-744-2294 Email: [email protected] Yusuke Nakazawa and Kazuto Ueda equally contributed to this study. Abstract Background: High-frequency oscillatory ventilation (HFOV) presents challenges for non-invasive CO₂ monitoring due to its rapid oscillations. This study examines the feasibility of instantaneous CO₂ partial pressure (INST CO₂) monitoring during HFOV with a capnometer equipped with a mainstream CO 2 sensor. Methods: This study included seven neonates receiving HFOV in the neonatal intensive care unit (NICU) at Shizuoka Children’s Hospital. INST CO₂ values were recorded over 3- and 5-min intervals surrounding each blood gas sampling to determine the maximum INST CO₂ value (INST CO₂ MX). The primary outcome was the correlation between INST CO₂ MX and arterial partial pressure of carbon dioxide (PCO₂). Results: A total of 216 paired INST CO 2 MX and PCO 2 values were analyzed. The coefficient of determination ( R 2 ) was 0.571 for INST CO 2 MX (3 min) and 0.579 for INST CO₂ MX (5 min). Univariable and multivariable analyses revealed that a lower fraction of inspired oxygen (FiO₂), reduced minute ventilation, and increased postnatal age were associated with improved concordance between INST CO₂ MX and PCO₂. Conclusion: INST CO₂ MX demonstrated a strong correlation with PCO 2 in neonates undergoing HFOV. This novel, non-invasive monitoring approach may serve as a valuable tool for neonatal respiratory management. Future research is needed to validate these findings in broader patient populations and across various ventilatory settings. Keywords exhaled carbon dioxide, instantaneous CO 2 , high-frequency oscillatory ventilation, very low birth weight infant Key Points What is already known on this topic Conventional methods for non-invasive CO 2 measurement are limited in high-frequency oscillatory ventilation (HFOV) due to the absence of distinguishable expiratory and inspiratory phases. What this study adds • The instantaneous CO 2 monitoring using the mainstream CO 2 sensor (cap-ONE, TG-980P, Nihon Kohden Corp., Tokyo) and the capnometer (OLG-3800, Nihon Kohden Corp., Tokyo) effectively measures expiratory CO 2 partial pressure as INST CO₂ MX in neonates undergoing HFOV. • INST CO₂ MX (5 min) showed a strong correlation with PCO 2 in neonates receiving HFOV. • Lower FiO 2 , reduced minute ventilation, and older postnatal age improved the degree of coincidence (DOC) between INST CO 2 MX and PCO 2 . How this study might affect research, practice, or policy INST CO₂ MX (5 min) could serve as a potentially beneficial tool for neonates undergoing HFOV. Introduction Maintaining optimal blood carbon dioxide (CO 2 ) levels is crucial for neonates under ventilatory management (1-3). Currently, the primary methods for monitoring CO 2 levels in ventilated neonates include blood gas analysis, transcutaneous blood gas monitoring, and expiratory CO 2 monitoring. While non-invasive and continuous monitoring methods are preferable, each approach has advantages and disadvantages. Blood gas analysis provides an accurate reflection of blood CO₂ levels. However, it requires invasive and often painful blood sampling (4, 5), which may increase the risk of infection and anemia due to frequent testing (6, 7). Moreover, this method does not allow for continuous monitoring. Transcutaneous blood gas monitoring enables continuous tracking of CO₂ levels (7) but carries risks of skin damage due to sensor heating, which reaches approximately 40°C (8, 9). Expiratory CO₂ monitoring measures the partial pressure of end-expiratory CO 2 . Although attaching an airway adaptor to the respiratory circuit increases dead space by approximately 0.5–1.0 mL, this method enables non-invasive, continuous CO₂ monitoring (9). The end-expiratory CO 2 partial pressure closely approximates alveolar and arterial CO 2 levels, making it a valuable method for estimating blood CO 2 levels. In this method, end-tidal CO 2 (ETCO 2 ) is measured by identifying expiratory and inspiratory phases from the CO 2 waveform and recording the CO 2 partial pressure at the end of expiration. However, in HFOV—widely used in neonatal care—gas exchange occurs at oscillation frequencies of approximately 10–15 Hz. As a result, a conventional CO₂ waveform that distinguishes between expiratory and inspiratory phases does not form, making ETCO₂ measurement unfeasible. Traditionally, it was believed that ETCO₂ could not be measured under HFOV due to the inability to differentiate between inhalation and exhalation phases. The instantaneous CO 2 mode, used in the mainstream CO 2 sensor (cap-ONE, TG-980P, Nihon Kohden Corp., Tokyo) and capnometer (OLG-3800, Nihon Kohden Corp., Tokyo) enables the measurement of instantaneous CO 2 partial pressure (INST CO 2 ) without requiring phase differentiation. The TG-980P sensor has a rapid response time, reduced from 120 to maximum values (INST CO₂ MX) within each second. By using the mainstream CO 2 sensor and capnometer, it may be possible to measure instantaneous CO 2 partial pressure within the airflow passing through the sensor, even in HFOV airflows with gas exchange frequencies of 10–15 Hz. Therefore, this study hypothesizes that this CO 2 sensor can estimate blood CO 2 levels and aims to evaluate its correlation with blood gas data, its agreement with PCO 2 , and its potential clinical applications in neonates. Subjects and methods Subjects This study included neonates born between July 2017 and January 2018 who underwent high-frequency oscillatory ventilation (HFOV) in the neonatal intensive care unit (NICU) of Shizuoka Children’s Hospital. The attending physician decided to initiate ventilatory support and was ventilated with HFOV in the NICU of Shizuoka Children’s Hospital. The decision to perform ventilatory management and to select the ventilator mode. The study was approved by the ethics committee of Shizuoka Children’s Hospital (Approval No. 20, 2017; renewal Approval No. 4, 2018), and written informed consent was obtained from the parents of all seven neonates included in the study. Measuring method A CO 2 sensor (TG-980P) airway adapter was placed between the ventilator circuit and the tracheal tube in neonates requiring HFOV. The ventilator used was the BabyLog VN500 (Dräger, Lübeck, Germany). The partial pressure of instantaneous CO₂ (INST CO₂) was continuously recorded in the instantaneous mode using the exhaled CO₂ monitor OLG-3800. Data were extracted from the OLG-3800 using a Nihon Kohden data extraction tool. Blood carbon dioxide levels (PCO 2 ) were measured via blood gas analysis using arterial, venous, or heel-prick blood samples and compared with INST CO 2 . Simultaneously, patient characteristics—including postnatal age, body weight, tracheal tube diameter, leak rate, HFOV settings (oxygen concentration, oscillation rate, amplitude, and mean airway pressure), minute ventilation rate, and single ventilation rate—were recorded at the time of blood collection. INST COMX INST CO 2 measured in steady flow mode represents instantaneous CO 2 partial pressure per second. Under HFOV, INST CO₂ fluctuates continuously, sometimes showing valid values and at other times showing minimal readings. To address this variability, INST CO₂ maximum (INST CO₂ MX) was defined as the highest recorded value within a specified time frame surrounding the PCO₂ measurement. INST CO₂ MX (3 min) refers to the maximum value within the 3 min before and after blood collection, while INST CO₂ MX (5 min) refers to the maximum value within the 5-min window. Factors influencing the concordance between PCO and INST COMX The degree of coincidence (DOC) between INST CO 2 MX and PCO 2 was calculated as follows: DOC = (PCO 2 -|PCO 2 -INST CO 2 MX|)/PCO 2 . Degree of coincidence thresholds of 80% and 90% were analyzed for INST CO 2 MX (3 min) and INST CO 2 MX (5 min). Factors evaluated included body weight at blood collection, postnatal age, tracheal tube diameter, pH, PCO 2 , HCO 3 − , BE, FiO 2 , mean airway pressure, frequency, amplitude, minute ventilation volume, and leakage rate. Both univariate and multivariate analyses were performed to identify parameters influencing DOC. Statistical analysis All statistical analyses were conducted using JMP 17.2.0 (SAS Institute Inc., North Carolina, USA). Correlations between PCO 2 and INST CO 2 MX (3 min) as well as between PCO 2 and INST CO 2 MX (5 min) were assessed using simple linear regression. Differences in PCO₂, INST CO₂ MX (3 min), and INST CO₂ MX (5 min) among the three groups were analyzed using Tukey’s honestly significant difference test. Simple and multiple logistic regression analyses were conducted to examine factors influencing DOC ≥80% and DOC ≥90% for both INST CO₂ MX (3 min) and INST CO₂ MX (5 min). A p value of <0.05 was considered statistically significant. Results Table 1. Patient characteristics Case 1 Female 23 weeks 2 days 549 5–36 77 Case 2 Male 24 weeks 0 days 433 11–71 51 Case 3 Male 24 weeks 0 days 687 2–46 44 Case 4 Female 24 weeks 0 days 717 4–19 9 Case 5 Female 25 weeks 4 days 763 12–20 13 Case 6 Male 27 weeks 6 days 627 15–18 11 Case 7 Female 29 weeks 0 days 647 13–15 11 Table 2. Univariate analysis of factors influencing DOC ≥80% or DOC ≥90% in INST CO 2 MX (3 min) and INST CO 2 MX (5 min) INST CO 2 MX (3 min) INST CO 2 MX (5 min) INST CO 2 MX (3 min) INST CO 2 MX (5 min) OR (95% CI) p OR (95% CI) p OR (95% CI) p OR (95% CI) p BW at data sampling 1.00 (1.00–1.00) n.s. 1.00 (1.00–1.00) n.s. 1.00 (1.00–1.00) n.s. 1.00 (1.00–1.00) n.s. Postnatal day 1.03 (1.01–1.05) 0.0026 1.04 (1.02–1.07) 0.0001 1.02 (1.00–1.04) n.s. ( p = 0.0718) 1.03 (1.01–1.05) 0.0041 Tube size 0.42 (0.11–1.64) n.s. 0.48 (0.12–1.88) n.s. 0.31 (0.069–1.41) n.s. 0.43 (0.10–1.79) n.s. pH 0.07 (0.014–3.21) n.s. 0.032 (0.00061–1.66) n.s. 0.010 (0.00011–0.94) 0.0435 0.034 (0.00051–2.25) n.s. pCO 2 1.03 (1.00–1.05) 0.0221 1.03 (1.01–1.06) 0.0042 1.02 (1.00–1.05) n.s. 1.02 (0.99–1.04) n.s. HCO 3 − 1.05 (0.99–1.12) n.s. 1.07 (1.01–1.14) 0.0246 1.00 (0.93–1.07) n.s. 1.00 (0.94–1.07) n.s. BE 1.04 (0.98–1.11) n.s. 1.06 (0.99–1.13) n.s. 0.98 (0.91–1.05) n.s. 0.98 (0.92–1.06) n.s. FiO 2 0.049 (0.0047–0.51) 0.0105 0.042(0.0039–0.45) 0.0076 0.041 (0.0026–0.63) 0.0194 0.025 (0.0017–0.31) 0.0041 MAP 1.45 (0.97–2.18) n.s. 1.49 (0.99–2.22) n.s. 0.93 (0.59–1.45) n.s. 1.03 (0.68–1.59) n.s. Amplitude 0.95 (0.90–1.00) n.s. 0.95 (0.90–1.01) n.s. 0.97 (0.91–1.03) n.s. 0.96 (0.90–1.02) n.s. TV 1.09 (0.95–1.25) n.s. 1.18 (0.98–1.41) 0.0373 1.04 (0.93–1.16) n.s. 1.10 (0.97–1.26) n.s. MV 0.14 (0.040–0.46) 0.0007 0.21 (0.064–0.68) 0.0067 0.066 (0.016–15.1) <0.0001 0.12 (0.034–0.45) 0.0009 % leak 1.02 (1.00–1.05) n.s. 1.02 (0.99–1.05) n.s. 1.02 (1.00–1.04) n.s. 1.03 (1.01–1.06) 0.0091 Note . BW, body weight; MAP, mean airway pressure; MV, minute volume; n.s., no statistically significant difference; TV, tidal volume. The values in the table represent p values ( p < 0.05). Table 3. Multivariate analysis of factors influencing DOC ≥80% or DOC ≥90% in INST CO 2 MX (3 min) and INST CO 2 MX (5 min) INST CO 2 MX (3 min) INST CO 2 MX (5 min) INST CO 2 MX (3 min) INST CO 2 MX (5 min) Factor OR (95% CI) p value Factor OR (95% CI) p value Factor OR (95% CI) p value Factor OR (95% CI) p value FiO 2 0.00059 (0.000015–0.019) 0.0001 FiO 2 0.000087 (0.0000018–0.0041) 0.00000 Postnatal day 1.08 (1.03–1.13) 0.00019 Postnatal day 1.07 (1.03–1.11) 0.00059 MV 0.070 (0.011–0.44) 0.0025 Postnatal day 1.09 (1.04–1.14) 0.00021 MV 0.058 (0.008–0.41) 0.0038 FiO 2 0.0028 (0.000063–0.13) 0.0022 MAP 1.84 (1.11–3.05) 0.016 MV 0.087 (0.013–0.58) 0.0073 BW at data sampling 0.017 (0.00026–1.16) 0.0078 MV 0.097 (0.015–0.59) 0.0011 Postnatal day 1.04 (1.00–1.08) 0.031 MAP 1.84 (1.10–3.07) 0.018 FiO 2 1.00 (0.99–1.00) 0.049 PCO 2 1.03 (0.99–1.07) 0.11 PCO 2 1.04 (1.00–1.08) 0.050 PCO 2 1.05 (1.00–1.09) 0.026 PCO 2 1.03 (0.99–1.07) 0.13 BW at data sampling 1.00 (1.00–1.00) 0.12 % leak 1.01 (0.97–1.04) 0.70 % leak 0.99 (0.96–1.03) 0.72 MAP 0.78 (0.44–1.38) 0.40 % leak 1.01 (0.98–1.05) 0.45 BW at data sampling 1.00 (1.00–1.00) 0.70 BW at data sampling 1.00 (1.00–1.00) 0.93 % leak 1.00 (0.97–1.03) 0.87 MAP 1.00 (0.59–1.70) 0.99 Note . BW, body weight; MAP, mean airway pressure; MV, minute volume; TV, tidal volume. The numerical values in the table represent p values. Patient characteristics in this study are summarized in Table 1. Of the seven patients, three (42.9%) were boys, and four (57.1%) were girls. The gestational age ranged from 23 weeks and 2 days to 29 weeks and 0 days (median: 24 weeks and 0 days), while birth weight ranged from 433 to 763 g (median: 647 g). INST CO₂ MX, PCO₂ concentration, and respiratory data were recorded for a total of 216 samples, with each patient contributing between nine and 77 samples. Correlation between PCO and INST CO MX (3 min) and INST CO MX (5 min) The correlation between PCO 2 and INST CO 2 MX (3 min) and INST CO 2 MX (5 min) was analyzed for all 216 samples. A significant correlation was observed between PCO 2 and INST CO 2 MX (3 min; r 2 = 0.571, p < 0.0001; Figure 1a) as well as between PCO 2 and INST CO 2 MX (5 min; r 2 = 0.579, p < 0.0001; Figure 1b). When comparing PCO₂ with INST CO₂ MX (3 min) and INST CO₂ MX (5 min), both INST CO₂ MX (3 min) and INST CO₂ MX (5 min) were significantly lower than PCO₂ (both p < 0.0001; Figure 1c). However, there was no significant difference between INST CO₂ MX (3 min) and INST CO₂ MX (5 min; p = 0.3285; Figure 1c). Degree of coincidence For INST CO 2 MX (3 min), 52.3% (113/216 samples) exhibited a DOC ≥80%, while 25.5% (55/216 samples) had a DOC ≥90% (Figure 2a). For INST CO 2 MX (5 min), 57.4% (124/216 samples) had a DOC ≥80%, and 31.5% (68/216 samples) had a DOC ≥90% (Figure 2b). Factors influencing DOC Univariate (Table 2) and multivariate (Table 3) analyses were conducted to identify factors influencing DOC at thresholds of 80% and 90% for INST CO 2 MX (3 min) and INST CO 2 MX (5 min). Univariate analysis revealed that DOC was significantly higher when FiO₂ and minute ventilation were lower. Additionally, for DOC ≥80% at INST CO₂ MX (3 min) and DOC ≥80% and DOC ≥90% at INST CO₂ MX (5 min), longer postnatal age was associated with increased concordance ( p < 0.05). For DOC ≥90% at INST CO₂ MX (3 min), there was a trend toward improved agreement with increasing postnatal age, although this difference did not reach statistical significance ( p = 0.0718; Table 2). Multivariate analysis further confirmed that low FiO 2 , low minute ventilation, and longer postnatal age were common factors influencing DOC ≥80% and DOC ≥90% at both INST CO₂ MX (3 min) and INST CO₂ MX (5 min; p < 0.05 for each, Table 3). Discussion This study aimed to assess the feasibility of monitoring CO 2 levels during HFOV using the instantaneous CO 2 mode with the mainstream CO 2 sensor TG-980P and the capnometer OLG-3800. The findings demonstrated a strong correlation between partial pressure of carbon dioxide (PCO 2 ) and instantaneous CO 2 maximum (INST CO 2 MX) at both 3- and 5-min intervals. Univariate analysis revealed significant agreement between INST CO 2 MX and PCO 2 when fractional inspired oxygen concentration (FiO 2 ) and minute ventilation were low, while multivariate analysis identified low FiO 2 , low minute ventilation, and longer postnatal age as influencing factors. The observed high correlation between PCO 2 and INST CO 2 MX (3 min) and INST CO 2 MX (5 min) can be attributed to three key factors: (a) the fast rise time of the CO 2 sensor, (b) the small mechanical dead space volume of the mainstream CO 2 sensor, and (c) the use of 3- and 5-min maximum values. Factor (a) enhances waveform reproduction accuracy, as a faster rise time ensures a waveform that more accurately reflects the input signal, which is consistent with previous research (10). This characteristic allows for the effective replication of both HFOV and spontaneous breathing waveforms. Factor (b) pertains to the small dead space volume (0.5 mL) of the CO 2 sensor’s airway adapter, which minimizes gas diffusion and improves waveform accuracy (11). In contrast, side-stream CO 2 sensors are associated with inaccuracies due to sampling delays and greater mechanical dead space (12). Factor (c) refers to the measurement approach, in which maximum CO 2 values are recorded over 3- and 5-min intervals. This method helps maintain a strong correlation with PCO 2 despite the continuous fluctuations in HFOV. A limitation of INST CO 2 MX (3 min) and INST CO 2 MX (5 min) is the inability to provide real-time measurements. Real-time CO 2 monitoring is valuable for detecting unplanned extubation and airway obstruction; however, these complications can also be identified through ventilator alarms and changes in patient parameters. The advantage of estimating PCO 2 outweighs the limitation of losing real-time measurements. Additionally, the present findings indicate that INST CO 2 MX (3 min) and INST CO 2 MX (5 min) were significantly lower than PCO 2 . Similar trends have been reported in conventional intermittent mandatory ventilation (IMV), where end-tidal CO 2 (ETCO 2 ) is significantly lower than PCO 2 in very-low-birth-weight infants. Therefore, the lower INST CO 2 values observed in this study were expected. Importantly, more than 50% of cases had a DOC ≥80%, suggesting that these values are clinically useful. Univariate and multivariate analyses identified lower FiO2, lower minute ventilation, and longer postnatal age as factors associated with increased DOC. This suggests that the correlation between INST CO2 and PCO2 improves as lung function and respiratory status stabilize with age, making INST CO2 measurements more reliable during the chronic phase compared with the acute phase. Previous studies of neonates under conventional IMV have reported similar findings, showing higher agreement between exhaled CO2 and blood gas CO2 in neonates with milder respiratory conditions, regardless of whether mainstream (8) or side-stream (12, 14) CO 2 sensors were used. Although the lower agreement observed during the acute phase may be a limitation, frequent blood sampling during this period allows for necessary corrections via blood gas analysis. Conversely, during the chronic phase, when blood sampling is less frequent, the higher concordance rate of INST CO2 MX suggests its potential clinical utility for noninvasive CO 2 monitoring. This study has several limitations. First, variability in blood sample types (arterial, venous, and capillary) may have influenced the results. However, previous studies have reported only an 11% discrepancy between specimen types (15), indicating that the present findings remain clinically relevant. Second, the small sample size (seven cases) and uneven distribution of samples per case (ranging from nine to 77 samples) may have affected statistical significance. Case-by-case correlation analysis showed a generally positive correlation between PCO 2 and INST CO 2 MX, except in one case (Case 6), where the small sample size may have limited statistical power. Additionally, the study revealed that a lower FiO 2 , a lower minute ventilation rate, and an older postnatal age were associated with higher DOC. This suggests that cases with prolonged HFOV management and a higher number of collected samples demonstrated stronger correlations, whereas cases in which HFOV was discontinued early showed weaker correlations due to fewer samples. Furthermore, this study included only low-birth-weight infants and utilized a single ventilator type. Variations in infant weight, ventilator type, and HFOV settings may influence the results. Therefore, expanding the study population and conducting further validation are necessary to generalize these findings. Conclusion This study demonstrated that the instantaneous CO 2 mode of the mainstream CO 2 sensor cap-ONE, TG-980P, in combination with the capnometerr OLG-3800, can effectively measure expiratory CO 2 partial pressure in neonates undergoing HFOV. These findings suggest that this monitoring approach is both practical and potentially beneficial for neonatal respiratory management. Acknowledgments The authors extend their gratitude to the staff of the NICU at Shizuoka Children’s Hospital for their invaluable assistance in data collection. Competing Interests Toshiki Aoki was an employee of Nihon Kohden. The equipment used in this study (cap-ONE TG-980P and OLG-3800) was provided by Nihon Kohden free of charge for the duration of the study. Author Contributions Yusuke Nakazawa: Conception and Study Design, Patient Recruitment, Data Analysis and Interpretation, and Manuscript Writing. Kazuto Ueda: Data Analysis and Interpretation, Manuscript Writing, and Final Manuscript Approval. Yoshihiro Tanahashi: Data Collection and Final Manuscript Approval. Toshiki Aoki: Conceptualization and Study Design, Patient Recruitment, Data Analysis and Interpretation, and Final Manuscript Approval. Yoshiaki Sato: Data Analysis and Interpretation and Final Manuscript Approval. Figures Figure 1. Correlation between PCO 2 and INST CO 2 MX. Simple linear regression analysis demonstrates a significant positive correlation between PCO 2 and (a) INST CO 2 MX (3 min; r 2 = 0.571, p < 0.0001, N = 216) and (b) INST CO 2 MX (5 min; r 2 = 0.579, p < 0.0001, N = 216). (c) Comparison of PCO 2 , INST CO 2 MX (3 min), and INST CO 2 MX (5 min). Both INST CO 2 MX (3 min) and INST CO 2 MX (5 min) were significantly lower than PCO 2 (both p < 0.0001), with no significant difference between INST CO 2 MX (3 min) and INST CO 2 MX (5 min; p = 0.3285). Data points represent individual measurements from the study population Figure 2. Degree of coincidence (DOC) at INST CO 2 MX. Bar chart illustrating the distribution of samples with DOC ≥80% and DOC ≥90% at (a) INST CO 2 MX (3 min) and (b) INST CO 2 MX (5 min). (a) At INST CO 2 MX (3 min), 52.3% (113/216) of samples had a DOC ≥80%, while 25.5% (55/216) of samples had a DOC ≥90%. (b) At CO 2 MX (5 min), 57.4% (124/216) of samples had a DOC ≥80%, while 31.5% (68/216) of samples achieved a DOC ≥90% Supplementary Material File (table 1.docx) Download 27.91 KB File (table 2.docx) Download 30.29 KB File (table 3.docx) Download 31.25 KB References 1. 1. National Guideline A. NICE Evidence Reviews Collection. 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Collection Pediatric Pulmonology Keywords exhaled carbon dioxide high-frequency oscillatory ventilation instantaneous co2 very low birth weight infant Authors Affiliations Yusuke Nakazawa Nakazawa Kodomo Clinic View all articles by this author Kazuto Ueda 0000-0003-3297-024X Nagoya Daigaku Igakubu Fuzoku Byoin View all articles by this author Yoshihiro Tanahashi Toyota Kinen Byoin View all articles by this author Toshiki Aoki Nakazawa Kodomo Clinic View all articles by this author YOSHIAKI SATO 0000-0001-6320-9176 [email protected] Nagoya Daigaku Igakubu Fuzoku Byoin View all articles by this author Metrics & Citations Metrics Article Usage 572 views 163 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Yusuke Nakazawa, Kazuto Ueda, Yoshihiro Tanahashi, et al. Exhaled Carbon Dioxide Monitoring Using Instantaneous CO2 Mode During High-Frequency Oscillatory Ventilation in Very Low Birth Weight Infants. Authorea . 20 May 2025. 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