Accuracy evaluation of mainstream and sidestream end-tidal carbon dioxide monitoring during noninvasive ventilation: a randomized crossover trial (MASCAT-NIV trial)

Background The end-tidal partial pressure of carbon dioxide (PETCO2) can be used to estimate the arterial partial pressure of carbon dioxide (PaCO2) in patients who undergo mechanical ventilation via endotracheal intubation. However, no reliable method for measuring PETCO2 during noninvasive ventilation (NIV) has been established. The purpose of this study was to evaluate the correlation and agreement between PaCO2 and PETCO2 measured by these two methods and to compare them in patients who underwent NIV after extubation. Methods This study was a randomized, open-label, crossover trial in a mixed intensive care unit. We included patients who were planned for NIV after extubation and for whom the difference between PETCO2 and PaCO2 was ≤ 5 mmHg. We compared mainstream capnography using an inner cup via face mask (the novel method) with sidestream capnography (the previous method) during NIV. The relationships between PaCO2 and PETCO2 were evaluated by computing the Pearson correlation coefficient, and the agreement between PaCO2 and PETCO2 was estimated using the Bland–Altman method. Results From April 2020 to October 2021, 60 patients were included to the study. PaCO2 and PETCO2 were well correlated in both methods (the novel methods: r = 0.92, P < 0.001; the previous method: r = 0.79, P < 0.001). Mean bias between PaCO2 and PETCO2 measured using the novel method was 2.70 (95% confidence interval [CI], 2.15–3.26) mmHg with 95% limits of agreement (LoA) ranging from − 1.61 to 7.02 mmHg, similar to the result of measurement during SBT (mean bias, 2.51; 95% CI, 2.00–3.02; 95% LoA, − 1.45 to 6.47 mmHg). In contrast, measurement using the previous method demonstrated a larger difference (mean bias, 6.22; 95% CI, 5.22–7.23; 95% LoA, − 1.54 to 13.99 mmHg). Conclusion The current study demonstrated that the novel PETCO2 measurement was superior to the previous method for PaCO2 prediction. During NIV, the novel method may collect as sufficient exhalation sample as during intubation. Continuous PETCO2 measurement combined with peripheral oxygen saturation monitoring is expected to be useful for early recognition of respiratory failure among high-risk patients after extubation. Trial registration UMIN-CTR UMIN000039459. Registered February 11, 2020. Supplementary Information The online version contains supplementary material available at 10.1186/s40560-022-00603-w.


Supplementary Results
Details of updated carlson comorbidity index ...…………………. 6 ..………………. 9-10 Appendix S1 Potential risks of post-extubation respiratory failure [1] Patients fulfilling at least 1 of the following criteria were considered at high risk of extubation failure: • Age older than 65 years • Heart failure as the primary indication for mechanical ventilation • Moderate to severe chronic obstructive pulmonary disease • Acute Physiology and Chronic Health Evaluation II score higher than 12 on extubation day • Body mass index of more than 30 (calculated as weight in kilograms divided by height in meters squared) • Airway patency problems • Including high risk of developing laryngeal edema • Inability to deal with respiratory secretions (inadequate cough reflex or suctioning >2 times within 8 hours before extubation) • Difficult or prolonged weaning, • A patient failing the first attempt at disconnection from mechanical ventilation • Two or more items of charlson comorbidity index • Mechanical ventilation for more than 7 days

Group Explanation
No weaning Patients never experienced any separation attempt Group 1 (Short weaning) The first separation attempt resulted in a termination of the weaning process within 24 hours (successful separation or early death) Group 2 (Difficult weaning) Weaning was terminated after more than 1 day but in less than 1 week after the first separation attempt (successful separation or death) The Smart Capnoline ® Plus (Oridion Medical 1987 Ltd., Jerusalem, Israel) is a nasal prong and oral scoop for use in non-intubated patients with the dual purpose of delivering oxygen and collecting exhalation from both the nose and mouth. The length of the cannula was approximately 255 cm, and the delay in CO2 measurement was approximately 240 ms. The patients were fitted with a face mask over the nasal prong.

Fig. S2
Bland-Altman plot of agreements between PaCO2 and PETCO2among patients according to leakage 1. Patients with small amount of leakage (total leakage < 40 L/min) a) For Bland-Altman analysis in patients using the previous method. Mean bias between PaCO2 and PETCO2 measured using the previous method was 6.50 mmHg with 95% LoA ranging from -3.23 to 16.23 mmHg. b) For Bland-Altman analysis in patients using the novel method. Mean bias between PaCO2 and PETCO2 measured using the novel method was 2.72 mmHg with 95% LoA ranging from -1.61 to 7.06 mmHg.
2. Patients with large amount of leakage (total leakage > 40 L/min) a) For Bland-Altman analysis in patients using the previous method. Mean bias between PaCO2 and PETCO2 measured using the previous method was 6.07 mmHg with 95% LoA ranging from -0.12 to 12.25 mmHg. b) For Bland-Altman analysis in patients using the novel method. Mean bias between PaCO2 and PETCO2 measured using the novel method was 2.64 mmHg with 95% LoA ranging from -1.37 to 6.64 mmHg.
In each plot, bias is represented by the dashed line. The LoA is represented by the gray zone. Abbreviations: LoA, limit of agreement; PETCO2, end-tidal partial pressure of carbon dioxide; PaCO2, arterial partial pressure of carbon dioxide; SBT, spontaneous breathing trial. Abbreviations: CI, confidence interval; PETCO2, end-tidal partial pressure of carbon dioxide; PaCO2, arterial partial pressure of carbon dioxide.