Comparison of Mainstream End Tidal Carbon Dioxide on Y-Piece Side Versus Patient Side of Heat and Moisture Exchanger Filters in Critically Ill Adult Patients: a prospective observational study

doi:10.21203/rs.3.rs-1619247/v1

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Comparison of Mainstream End Tidal Carbon Dioxide on Y-Piece Side Versus Patient Side of Heat and Moisture Exchanger Filters in Critically Ill Adult Patients: a prospective observational study

https://doi.org/10.21203/rs.3.rs-1619247/v1

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published 02 Aug, 2022

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Introduction: Whether HMEF impairs the accuracy of mainstream EtCO₂ measured on the Y-piece (filtered) side of HMEF compared to that on the patient (unfiltered) side is unclear.

Methods: We conducted a prospective observational method comparison study in a teaching hospital in Japan between July 2019 and December 2019. Critically ill adult subjects receiving mechanical ventilation with HMEF were included. We performed a noninferiority comparison of the accuracy of EtCO₂ measurements on the two sides of HMEF. The accuracy was measured by the absolute difference between PaCO₂ and EtCO₂. We set the non-inferiority margin at +1 mmHg in accuracy difference between the Y-piece side and the patient side of HMEF. We also assessed the agreement between PaCO₂ and EtCO₂ using Bland-Altman analysis.

Results: Among thirty-seven subjects, the accuracy difference was -0.14 mmHg (95% CI, -0.58–0.29), and the upper 95% CI limit did not exceed the predefined margin of + 1 mmHg, establishing non-inferiority of EtCO₂ on the Y-piece side of HMEF (P for non-inferiority <0.001). In the Bland-Altman analyses, 95% limits of agreement between PaCO₂ and EtCO₂ were similar in both sides of HMEF (Y-piece side, -8.67–+10.65 mmHg; patient side, -8.93–+10.67 mmHg).

Conclusions: The accuracy of mainstream EtCO₂ measurements on the Y-piece side of HMEF was noninferior to that on the patient side in critically ill adult subjects. Mechanically ventilated adult subjects could be accurately monitored with mainstream EtCO₂ on the Y-piece side of the HMEF unless their tidal volume was extremely low.

capnography

end-tidal carbon dioxide

humidifier

Intensive care unit

mechanical ventilation

monitoring.

End-tidal carbon dioxide (EtCO₂) monitoring is a non-invasive, continuous measurement of exhaled carbon dioxide (CO₂) that offers real-time information about patients’ ventilation, perfusion, and metabolism [1–4]. In ICU, EtCO₂ monitoring ensures the integrity of the ventilator circuit and assists the titration of mechanical ventilation [5]. Furthermore, a detailed assessment of EtCO₂ provides valuable insights into pathological respiratory physiology, such as increased physiologic dead space in critically ill patients [5]. The importance of EtCO₂ monitoring for patient safety has been increasingly recognized, and many professional societies have adopted its use as a standard of practice [3].

Heat and moisture exchanger filters (HMEFs) are widely used humidifier devices, especially during the current coronavirus disease 2019 pandemic for their filtering function. In ventilator circuits with HMEF, an EtCO₂ sensor is placed either on the patient side or the Y-piece side of HMEF. On the patient side, exhaled gas reaches an EtCO₂ sensor before being filtered by HMEF, thereby coughed up secretions from patients can contaminate the sensor and interrupt continuous monitoring. On the Y-piece side, in contrast, the exhaled gas is measured after being filtered by the HMEF, reducing the risk of sensor contamination. Current anesthesia guidance during the coronavirus disease 2019 pandemic recommends using an HMEF and sampling gas from the Y-piece (filtered) side of the HMEF [6]. However, HMEF alters the components of exhaled gas during filtering, and thus affects EtCO₂ values and waveforms [7]. Previous studies reported that EtCO₂ measured with the sidestream method on the Y-piece side of HMEF showed lower values than that on the patient side [8, 9]. Inaccurately low EtCO₂ values could lead to misrecognition of CO₂ retention and threaten patient safety [10].

In the ICU, the mainstream EtCO₂ measurement is preferred because it has a faster response time than the sidestream method [5]. Yet, the accuracy of mainstream EtCO₂ on the Y-piece side of HMEF has not been evaluated [5]. This study aimed to investigate whether the accuracy of mainstream EtCO₂ measurement on the Y-piece side of the HMEF was noninferior to that on the patient side in critically ill adult patients receiving mechanical ventilation. This non-inferiority design is based on the benefits conferred by HMEF when measuring on the Y-piece side.

Study Design and Setting:

This study was approved by the institutional review board (2019-No.17). The requirement for written informed consent was waived by the institutional review board. The protocol was registered a priori in the UMIN-CTR (UMIN-CTR ID: 000037317).

This was a single-center prospective observational method comparison study in a tertiary care teaching hospital in Japan, which had 550 beds with 12 general ICU beds, conducted between July 2019 and December 2019.

Selection of the Patients

We prospectively screened all patients of mechanical ventilation in the ICU between July 16, 2019, and December 9, 2019. Patients were eligible when they were adults (≥ 20 years) receiving invasive mechanical ventilation, HMEF was used in the ventilator circuit, and an arterial line was placed. Patients were excluded when they were pregnant, previously enrolled in this study, patients or next of kin refused study participation, or they met any of the following safety criteria. The safety criteria were: PEEP ≥ 10 cmH₂O, fraction of inspired oxygen ≥ 0.6, heart rate < 40 bpm or 130 ≥ bpm, mean blood pressure < 60 mmHg or ≥ 110 mmHg, saturation of percutaneous oxygen < 90%, respiratory rate ≥ 40 breaths/min, or temperature < 36 or ≥ 38.5°C. These criteria followed the Japanese guidelines for early mobilization of mechanically ventilated patients [11, 12]. We also excluded patients when treating physicians judged the patient as inappropriate for study participation.

Measurement of EtCO₂

For eligible patients, we measured EtCO₂ on the two sides of the HMEF and PaCO₂ during the daytime (8:00–17:00) on weekdays. The timing of the measurements was based on the clinical indication of arterial blood gas analysis. We measured the first EtCO₂ on either the Y-piece side or the patient side of the HMEF, where the EtCO₂ sensor was placed (Fig. 1). Then, we switched the EtCO₂ sensor to the opposite side of the HMEF and measured the second EtCO₂. On each side, we averaged EtCO₂ from three consecutive breaths. CO₂ sensor zeroing was performed when we switched the position of the sensor, or the baseline flow did not return to zero in the capnography. Clinical engineers in the study team measured EtCO₂, simultaneously collected arterial blood, and submitted it for blood gas analysis to measure PaCO₂. Each EtCO₂ reading was performed before the results of blood gas analysis returned; thus, readers of EtCO₂ were unaware of the PaCO₂ value. The EtCO₂ sensor was Capnostat5 (Respironics), HMEF was Hygrobag S (Medtronic), and the blood gas analyzer was ABL800 (RADIOMETER).

We recorded patient demographics and clinical characteristics, including acute physiology and chronic health evaluation II (APACHE II) scores [13], vital signs, and ventilatory parameters, as shown in Tables 1 and 2. All patients were followed up until hospital discharge, and hospital outcomes were recorded.

Table 1

Patients Demographics, Characteristics at EtCO2 measurements and Outcomes.
Variables			N = 37
Demographics
	Age (median [IQR])		70 [60–79]
	Male (%)		21 (57%)
	BMI (median [IQR])		21.8 [19.6–25.3]
	Current or former smoker (%)		17 (46%)
	Location prior to ICU admission (%)
		Operating room	20 (54%)
		Emergency room	11 (30%)
		Ward	6 (16%)
	ICU admission diagnosis (%)
		Cardiovascular	7 (19%)
		Respiratory	4 (11%)
		Gastrointestinal	10 (27%)
		Neurological	8 (22%)
		Metabolic	2 (5%)
		Genitourinary	1 (3%)
		Obstetrics and gynecology	2 (5%)
		Musculoskeletal	1 (3%)
		Trauma	2 (5%)
	APACHE II score (median [IQR])		19 [16–25]
Characteristics at EtCO₂ measurements
	Time from intubation (median [IQR]), hour		21 [14–24]
	Days form ICU admission (median [IQR]), day		2 [2–2]
	Vital signs during measurement (median [IQR])
		Systolic blood pressure, mm Hg	129 [109–144]
		Diastolic blood pressure, mm Hg	63 [56–72]
		Mean arterial pressure, mm Hg	88 [77–101]
		Heart rate, /min	82 [72–95]
		Body temperature, Celsius	36.9 [36.6–37.4]
		Percutaneous oxygen saturation (%)	98 [97–99]
	Arterial blood gas analysis and ventilator settings (median [IQR])
		PaCO₂, mm Hg	38.2 [34.9–41.6]
		PaO₂, mm Hg	93.0 [83.8–124.0]
		pH	7.43 [7.42–7.45]
		Bicarbonate, mmol/L	25.3 [22.5–27.1]
		P/F ratio	364 [317–410]
		FiO₂	0.25 [0.21–0.35]
		PEEP, cm H₂O	5 [5–5]
Patient outcomes
	ICU stay (median [IQR]), day		4 [2–7]
	Survival discharge		20 (54%)
	Transfer		11 (30%)
	Death		6 (16%)
EtCO₂, end-tidal carbon dioxide; IQR, interquartile range; BMI, body mass index; ICU, Intensive Care Unit; APACHE, acute physiology and chronic health evaluation; PaCO₂, partial pressure of arterial carbon dioxide; PaO₂, partial pressure of arterial oxygen; P/F ratio, the ratio of arterial oxygen partial pressure to fraction of inspired oxygen; FiO₂, fraction of inspired oxygen; PEEP, positive end expiratory pressure.

Table 2

Paired Observations on Y-piece side and patient side of HMEF.
		Y-piece side N = 37	Patient side N = 37	Difference * (Y-piece side - Patient side)	P value†
EtCO₂, (mean [SD]), mm Hg		37.4 (5.5)	37.5 (6.1)	-0.1 (1.6)	0.65
Absolute difference between PaCO₂ and EtCO₂, (mean [SD]), mm Hg		3.6 (3.4)	3.8 (3.3)	-0.1 (1.5)	0.58
Ventilator monitoring values during measurement, (mean [SD])
	Tidal volume, mL	418 (137)	431 (154)	-3.1 (40.7)	0.64
	Minute volume, L	6.2 (1.7)	6.3 (1.7)	-0.2 (0.6)	0.10
	Respiratory rate, /min	17 (4.7)	17 (4.9)	-0.1 (1.2)	0.79
	Peak pressure, cm H₂O	14.1 (5.0)	14.2 (4.8)	-0.1 (0.7)	0.53
HMEF, heat and moisture exchanger filter; EtCO₂, end-tidal carbon dioxide; SD, standard deviation.
* Differences between paired observations.
† Two-tailed P values of the paired samples t-test.

Statistical analysis

We labeled EtCO₂ measured on the Y-piece side of HMEF as “the index measurement,” EtCO₂ measured on the patient side as “the alternative measurement,” and PaCO₂ as “the reference standard [14].” We assessed the accuracy of EtCO₂ measurements by the absolute difference between PaCO₂ and EtCO₂ [15]. We defined ΔY-piece side as the absolute difference between PaCO₂ and EtCO₂ measured on the Y-piece side of HMEF, and Δpatient side as the absolute difference between PaCO₂ and EtCO₂ measured on the patient side. We compared the accuracy of the two EtCO₂ measurements by the accuracy difference defined as ΔY-piece side - Δpatient side. We calculated the accuracy difference in each patient and estimated the mean and 95% CI.

In the non-inferiority comparison of accuracies of the two EtCO₂ measurements, we set a priori the non-inferiority margin of + 1 mmHg in accuracy difference. The size of the margin was determined from a clinical standpoint and previous reports [8, 9, 16]. We declared non-inferiority of the Y-piece side if the upper limit of the CI for accuracy difference did not exceed the predefined margin of + 1 mmHg. This means that we accepted the Y-piece side if the absolute difference between PaCO₂ and EtCO₂ on the Y-piece side was not more than + 1 mmHg compared to the absolute difference between PaCO₂ and EtCO₂ on the patient side. We calculated the P-value for non-inferiority using two one-sided paired-sample t-tests. From the pilot observation, SD of the accuracy difference between the Y-piece side and the patient side was estimated at 1.5 mmHg. The calculated sample size for the non-inferiority test was 35 paired observations with a 5% one-sided significance level and 90% power.

In addition, on each side of the HMEF, we assessed the agreement between PaCO₂ and EtCO₂ using Bland-Altman analysis [17]. We graphically presented the variation of differences between PaCO₂ and EtCO₂ against their average (Bland-Altman plot). As a measure of lack of agreement, we estimated the mean difference and 95% limits of agreement [17]. We performed Bland-Altman analysis for EtCO₂ on the Y-piece side and EtCO₂ on the patient side separately, then compared the graphics and statistics of the two analyses. According to the reporting standards for Bland-Altman analysis, to ensure that the limits of agreement were meaningful summary statistics of the differences, we checked the following assumptions: repeatability, normality, and constant variation. Repeatability represents within-patient variation in repeated measurements of EtCO₂ in the same patient [18]. We recorded three EtCO₂ measurements per position per patient and assessed the repeatability of EtCO₂. We graphically checked whether the differences were normally distributed and whether variations in the differences were constant across the range of measurements.

Previous studies reported that differences between EtCO₂ on the Y-piece side and EtCO₂ on the patient side of HMEF were greater when the tidal volume was small [8, 9]. Therefore, we evaluated the relationship between the differences and tidal volume using Pearson’s correlation coefficient and linear regression.

We presented patient characteristics as medians with interquartile ranges (IQR) for continuous variables and as proportions for categorical variables. We presented paired observations of EtCO₂ values, absolute differences, and ventilator monitoring values on the two sides of the HMEF as means with SDs. The means of differences between paired observations were compared with paired samples t-test, and two-sided P-values were reported. All statistical analyses were performed using R (The R Foundation for Statistical Computing, ver.3.5.2) and EZR (Saitama Medical Center, Jichi Medical University, ver.1.40), which is a graphical user interface for R [19]. Figure 3,4 and Supplemental Fig. 1 (Supplementary Information 1) were created using JMP (ver.16.1.0).

Between July 16, 2019, and December 9, 2019, there were 167 patients on mechanical ventilation in the ICU, and screening for full eligibility criteria was completed in 132 of them (Fig. 2). Among the 52 eligible patients, we excluded 15 that met the exclusion criteria, leaving 37 patients in the study. In all 37 patients, two EtCO₂ measurements and PaCO₂ were collected. The median age was 70 years (IQR, 60–79), 57% (21/37) were male, 76% (28/37) were emergency ICU admissions, and the median acute physiology and chronic health evaluation II score was 19 (IQR, 16–25) (Table 1). The major diagnoses were cardiovascular (19% [7/37]), respiratory (11% [4/37]), gastrointestinal (27% [10/37]), and neurological diseases (22% [8/37]).

At the time of EtCO₂ measurements, the median number of days from ICU admission was 2 days (IQR, 2–2), and the median time from intubation was 21 hours (IQR, 14–24). Most of the patients had stable vital signs; the median systolic blood pressure was 129 mmHg (IQR, 109–144), body temperature was 36.9°C (IQR, 36.6–37.4), and respiratory rate was 16 breaths per minute (IQR, 14–19). The median partial pressure of arterial oxygen was 93.0 mmHg (IQR, 83.8–124.0), PaCO₂ was 38.2 mmHg (IQR, 34.9–41.6), and the ratio of partial pressure arterial oxygen to fraction of inspired oxygen was 364 (IQR, 317–410). The ventilator mode was continuous spontaneous ventilation in 46% (17/37) of the patients. The median fraction of inspired oxygen was 0.25 (IQR, 0.21–0.35) and PEEP was 5 cmH₂O (IQR, 5–5). The median ICU stay was 4 days (IQR, 2–7), and the hospital mortality rate was 16% (6/37).

The paired observations on the Y-piece side and the patient side of the HMEF are presented in Table 2. The means of EtCO₂ were 37.4 mmHg (SD, 5.5) and 37.5 mmHg (SD, 6.1) on the Y-piece side and the patient side, respectively. The mean difference in EtCO₂ (Y-piece side – patient side) was − 0.1 (SD, 1.6). The estimated accuracy difference (ΔY-piece side - Δpatient side) was − 0.14 mmHg (95% CI, -0.58–0.29). The upper limit of the CI for accuracy difference did not exceed the predefined margin of + 1 mmHg, establishing non-inferiority (P for non-inferiority < 0.001) (Fig. 3).

In the Bland-Altman analyses, the mean difference between PaCO₂ and EtCO₂ on the Y-piece side was 0.99 mmHg (95% CI, -0.66–2.63), and 95% limits of agreement was − 8.67 mmHg (95% CI, -11.51– -5.84) to 10.65 mmHg (95% CI, 7.82–13.49). The mean difference between PaCO₂ and EtCO₂ on the patient side was 0.87 mmHg (95% CI, -0.80–2.54), and 95% limits of agreement was − 8.93 mmHg (95% CI, -11.81– -6.06) to 10.67 mmHg (95% CI, 7.80–13.55) (Supplementary Information 1: Supplemental Table 1). The estimated 95% limits of agreement were almost identical, indicating that the degree of agreement between PaCO₂ and EtCO₂ was similar on the Y-piece side and the patient side (Fig. 4). The square root of within-patient variance of EtCO₂ was 0.65 mmHg on the Y-piece side and 1.01 mmHg on the patient side, suggesting that the repeatability of the two EtCO₂ were sufficient. Histograms of differences between PaCO₂ and each of the two EtCO₂ measurements showed roughly normal distributions. Graphical inspection revealed that the variations in the differences were constant across the range of measurements (Fig. 4).

The relationship between tidal volume and difference in Y-piece side EtCO₂ and patient-side EtCO₂ are assessed in Supplemental Fig. 1 (Supplementary Information 1). There was no significant linear relationship (regression coefficient, -0.001 [95% CI, -0.005–0.003], correlation coefficient, -0.096).

In this prospective method comparison study, we found that the accuracy of mainstream EtCO₂ measurement on the Y-piece side of HMEF was noninferior to that on the patient side. In adult ventilated patients using HMEF, our results support measuring EtCO₂ with the mainstream method on the Y-piece side of HMEF.

Relation to previous studies

Our observation contrasted with previous studies, which showed that sidestream EtCO₂ measurement on the Y-piece side of HMEF was lower than that on the patient side [8, 9, 20]. A study investigating 30 adult patients under general anesthesia reported that sidestream EtCO₂ on the Y-piece side of the breathing filter was lower than that on the patient side by -8.85 mmHg (95% CI, -19.58– -1.95) [8]. Similar results were reported in healthy children and critically ill adult patients [9, 20]. Several mechanisms were proposed as the reason for the lower EtCO₂ values on the Y-piece side of HMEF. First, the internal volume of the HMEF serves as an additional dead space in the ventilator circuit. While exhaled gas passes through the HMEF, the dead space from the HMEF is added to the exhaled gas. This addition dilutes exhaled CO₂ and thus lowers the Y-piece side of EtCO₂ [7]. The impact of dilution is particularly large in patients with low tidal volumes, such as pediatric patients [7]. Second, the sidestream capnometer aspirates a large volume of gas (150–200 ml/min) from the ventilator circuit during sampling [21]. The sampled gas tends to entrain fresh gas from the ventilator circuit, resulting in dilution of exhaled CO₂ [21]. The dilution of EtCO₂ with fresh gas entrainment is pronounced as the sampling site becomes closer to the ventilator, that is on the Y-piece side of HMEF [22]. These dilution effects explain the lower EtCO₂ values on the Y-piece side of HMEF.

In contrast, using the mainstream method, we found that the absolute difference between PaCO₂ and EtCO₂ was similar on both sides of the HMEF. The mainstream method of EtCO₂ measurement avoids mixing with fresh gas and does not dilute exhaled CO₂ during sampling. In adult patients undergoing brain surgery, mainstream EtCO₂ showed better agreement with PaCO₂ than sidestream EtCO₂ [21]. Considering these findings, we suspected that the sidestream method with large sampling volume was a major source of error in the Y-piece side EtCO₂ in previous studies [8, 9, 20]. Our study results also suggested that the dilution effect of dead space from HMEF was clinically small in adult patients with tidal volume within the observed range in this study (5–95 percentile range, 254–576 ml) [20]. Indeed, we could not find a significant relationship between tidal volume and difference in Y-piece side EtCO₂ and patient side EtCO₂ (Supplementary Information 1: Supplemental Fig. 1). In summary, we thought that the mainstream method and sufficient tidal volume were the main factors that maintained the accuracy of EtCO₂ on the Y-piece side of the HMEF in our study.

Implications for clinicians

Placing the EtCO₂ sensor on the Y-piece side of the HMEF has several advantages. HMEF prevents patients’ secretions from interfering with the EtCO₂ sensors. Further, this position reduced the risk of health care workers’ exposure to unfiltered exhaled gases, during circuit disconnection or zeroing EtCO₂ sensor [23]. HMEF is a cost-effective choice for humidification in situations including prolonged mechanical ventilation with less active diseases, recovering patients after elective surgery, patients without thick secretions, and cases of over-humidification with a heated humidifier [24]. Our study results suggested that patients in these situations could be safely monitored with mainstream EtCO2 on the Y-piece side of HMEF. The results of our study provide supporting evidence for current guidance on HMEF use during the coronavirus disease 2019 pandemic. (COVID 19 Anesthesia Machines and Equipment Maintenance. Anesthesia Patient Safety Foundation [6].

Of note, in small pediatric patients, it was reported that the dead space applied by HMEF induced CO₂ retention and EtCO₂ monitoring on the Y-piece side of HMEF failed to detect elevated CO₂ [10, 25]. Our study results should not be applied to pediatric patients.

Strengths and weaknesses of this study

We prospectively investigated the accuracy of mainstream EtCO₂ measurements. The readers of EtCO₂ were unaware of PaCO₂, which was the reference standard in this study. Our declaration of non-inferiority was based on an a priori defined non-inferiority margin. Our conclusion was based on the assessment of both mean difference and limits of agreement, following the reporting standards for method comparison study [18]. These features contributed to the quality of accuracy comparison in this study.

This study had several limitations. First, the included patients were selected as appropriate cases for HMEF; thus, they had relatively stable respiratory status. Our results were not directly applicable to patients under more severe conditions, such as extreme hypercapnia or very low tidal volume. We believe that such a severe patient is not a good candidate for the HMEF circuit. Second, the median time from HMEF placement to EtCO₂ measurement was 16 hours (IQR, 11–19). We could not refer to the accuracy of EtCO₂ under conditions with prolonged use of HMEF, although a study showed that 120-hour use of HMEFs did not increase their resistance [26]. Third, the choice of the non-inferiority margin was based on clinical judgment. However, we set a stricter margin (1 mmHg) for non-inferiority compared to a previous study (5 mmHg) [16]. Also, the non-inferiority test was conducted according to the prespecified analysis plan including sample size calculation and the pre-defined non-inferiority margin [27]. Fourth, despite prospective screening, 35 of 167 patients on mechanical ventilation could not undergo screening for the eligibility criteria. These patients required mechanical ventilation for a short period and were extubated before screening. Thus, their characteristics were considered to be similar to those of the study patients. We believe that excluding them from the analysis did not materially affect the study results. Fourth, despite prospective screening, 35 of 167 patients on mechanical ventilation could not undergo screening for the eligibility criteria. These patients required mechanical ventilation for a short period and were extubated before screening. Thus, their characteristics were considered to be similar to those of the study patients. We believe that excluding them from the analysis did not materially affect the study results. Fifth, we examined only one HMEF device (Hygrobag S, Medtronic), which had 45 ml of dead space. It might not be appropriate that we directly apply the study results to other HMEF devices, particularly those with larger dead space [28].

The accuracy of mainstream EtCO₂ measurements on the Y-piece side of HMEF was noninferior to that on the patient side in critically ill adult patients. Mechanically ventilated adult patients humidified with HMEF could be safely monitored with mainstream EtCO₂ on the Y-piece side of the HMEF unless their tidal volume was extremely low. This method of EtCO₂ measurement reduces sensor malfunctions and the risk of health care workers’ exposure to unfiltered gas while maintaining accuracy.

confidence interval

CO₂

carbon dioxide

EtCO₂

End-tidal carbon dioxide

HMEF

heat and moisture exchanger filter

ICU

intensive care unit

IQR

interquartile range

PaCO₂

partial pressure of arterial carbon dioxide

PEEP

positive end expiratory pressure

standard deviation.

Ethics approval and consent to participate

This study was approved by the Research ethics committee of Okinawa Chubu Prefectural Hospital (2019-No.17). The requirement for written informed consent was waived by the institutional review board.

Consent for publication

Not applicable.

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interests

All the authors declare that they have no conflicts of interest.

Funding

Not applicable.

Authors' contributions

ST, IN and JI designed the study, conceptualized the data acquisition, acquired the data, and interpreted the data. ST, IN, and KG contributed to the data analysis. JI supervised the study. IN and ST wrote the first draft of the manuscript, and all authors commented on the previous version of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We acknowledge Tamie Yorimitsu, M.D., Shinya Kozawa, C.E.T., Daisuke Matayoshi, C.E.T., Takashi Kameya, C.E.T., Daichi Kaneshima, C.E.T., Ikki Shimoji, C.E.T., Michiko Kaneshima, C.E.T., Hideo Tamaki, R.N., Eikatsu Senaha R.N., and Miwako Hokama, R.N., in Intensive Care Unit, Okinawa Prefectural Chubu Hospital, Uruma, Okinawa, Japan for their contributions to data collection.

Authors' information (optional)

Satoshi Tamashiro and Izumi Nakayama have contributed equally to this work and share first authorship.

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No competing interests reported.

EtCO2SupplementaryInformationMay022022.docx
Supplementary Information File name: Supplementary Information 1File format: word file (.docx)Title of data: Supplementary InformationDescription of data:Supplemental Table 1: Mean differences and 95% limits of agreement in Bland-Altman analyses.Supplemental Figure 1: The relationship between tidal volume and differences in Y-piece side EtCO₂ and patient side EtCO₂. Differences between Y-piece side EtCO₂ and patient-side EtCO₂ were plotted against tidal volume. The tidal volume was the average of tidal volume at the time of the Y-piece side EtCO₂ measurement and tidal volume at the time of the patient side EtCO₂ measurement. Pearson’s correlation coefficient and regression coefficient of unadjusted linear regression of EtCO₂ differences on tidal volume are presented. The fitted regression line with 95% CI (blue-tinged area) is presented.

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Comparison of Mainstream End Tidal Carbon Dioxide on Y-Piece Side Versus Patient Side of Heat and Moisture Exchanger Filters in Critically Ill Adult Patients: a prospective observational study

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Study Design and Setting:

Selection of the Patients

Measurement of EtCO₂

Statistical analysis

Results

Discussion

Relation to previous studies

Implications for clinicians

Strengths and weaknesses of this study

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1

Comparison of Mainstream End Tidal Carbon Dioxide on Y-Piece Side Versus Patient Side of Heat and Moisture Exchanger Filters in Critically Ill Adult Patients: a prospective observational study

Status:

Journal Publication

Version 1

Abstract

Figures

Introduction

Methods

Study Design and Setting:

Selection of the Patients

Measurement of EtCO2

Statistical analysis

Results

Discussion

Relation to previous studies

Implications for clinicians

Strengths and weaknesses of this study

Conclusions

Abbreviations

Declarations

References

Additional Declarations

Supplementary Files

Status:

Journal Publication

Version 1

Measurement of EtCO₂