CC BY 4.0 · Journal of Child Science 2020; 10(01): e80-e86
DOI: 10.1055/s-0040-1714114
Original Article

Capnography in Pediatric Critical Care Unit and Correlation of End-Tidal and Arterial Carbon Dioxide in Ventilated Children

Akhil Krishnamoorthy
1  SVPPGIP, SCB Medical College, Cuttack, Odisha, India
Bijay Kumar Meher
2  Bhima Bhoi Medical College and Hospital, Balangir, Odisha, India
Deepti Damayanty Pradhan
3  KIMS, Bhubaneswar, Odisha, India
Saroj Kumar Satpathy
4  Department of Pediatrics, SVPPGIP, SCB Medical College, Cuttack, Odisha, India
› Author Affiliations
Funding None.


Recording of end-tidal carbon dioxide (EtCO2) noninvasively reflects a real-time estimation of arterial carbon dioxide (PaCO2 [partial pressure of CO2]). However, as the EtCO2 is dependent on metabolism, perfusion, and ventilation, predicting PaCO2 from EtCO2 is not linear. The objective of the study was to find out the predictability of PaCO2 from EtCO2 in PICU and to evaluate the factors affecting the correlation of EtCO2 and PaCO2 in critically ill ventilated children. The design involved was prospective observational study. The setting discussed over here is that of pediatric intensive care unit (PICU) of tertiary care hospital. A total of 160 children between 1 month and 14 years received mechanical ventilation. EtCO2, PaCO2, PaO2/FiO2 (PF) ratio, oxygenation index (OI), and ventilation index (VI) are the factors involved in main outcome measures. A total of 535 pairs of EtCO2 and PaCO2 were recorded in 160 ventilated children during the stable hemodynamic state. Mean age and weight (Z-score) of patients were 31.15 ± 40.46 months and −2.10 ± 1.58, respectively. EtCO2 and PaCO2 differences were normal (2–5 mm of Hg) in 393 (73.5%) pairs. High gradient (>5 mm of Hg) was mostly found with children with pneumonia, prolonged ventilation, and pressure mode of ventilation (p < 0.05). EtCO2 had a strong positive correlation with PaCO2 (r = 0.723, 95% confidence interval [CI] = 0.68 and 0.76) and not significantly affected by PF ratio or OI. However, presence of pneumonia and high ventilation index (VI > 20) adversely affected the relationship with poor correlation coefficient (r = 0.449, 95% CI = 0.30, 0.58 and r = 0.227, 95% CI = 0.03, 0.41, respectively). EtCO2 reading showed good validity to predict PaCO2 and not affected by oxygenation parameters. The correlation was affected by the presence of pneumonia and high ventilation index; hence it is recommended to monitor PaCO2 invasively in these patients till a good correlation is established.



In the pediatric intensive care unit (PICU), to ensure proper patient care and professional credibility, monitoring of CO2 and O2 is the recommended “minimum guidelines and levels of care” by American Academy of Pediatrics. Arterial blood gas (ABG) analysis is considered the gold standard in monitoring sick children on a mechanical ventilator. ABG sampling is costly, time-consuming, needs training, invasive with a risk of infection, and provides a snapshot view into the condition of the patient. Pulse oximetry and capnography provide noninvasive and real-time monitoring in PICU. Pulse oximetry provides predictable information about oxygenation. As capnography is dependent on metabolism, perfusion, and ventilation of the patient, it does not provide reliable information on ventilation during hemodynamic instability. Also, in conditions with increased physiological dead space (VD or dead space ventilation), the arterial carbon dioxide (PaCO2 or partial pressure of CO2) and end-tidal carbon dioxide (EtCO2) gradients are increased, and the correlation is affected.[1]

EtCO2 monitoring is the standard of care during procedures such as intubations and sedations and also used in a variety of clinical situations. However, EtCO2 may be underused in pediatric settings.[2] There is insufficient data for the use of capnography in PICU as a substitute for repeated ABG sampling in resource-poor settings and parameters affecting noncorrelation of EtCO2 with PaCO2.. Hence, this study was designed to assess how reliably EtCO2 predicts PaCO2 in critically sick ventilated infants and children in PICU and, to find out the different parameters which may affect the correlation.



Study Design

This was a prospective study done at PICU of a tertiary care hospital in India. Approval was obtained from the Institutional Ethical Committee. Informed consent was obtained from the parents before enrolling in the study.



All critically ill children from 1 month to 14 years admitted to PICU and requiring mechanical ventilation were included for the study. Patients diagnosed with or suspected of congenital cyanotic heart disease were excluded from the study as intracardiac shunting is likely to cause an obligatory difference between arterial and EtCO2.


Data Collection

After obtaining informed written consent from the parents, mechanically ventilated patients were selected from PICU according to inclusion and exclusion criteria. The patients were intubated with appropriate size endotracheal tube and ventilated using Puritan Bennet 840 Ventilator or Maquet (servo-I) ventilator in various modes like synchronized intermittent mandatory ventilation (SIMV) or assist-control modes. Humidifier (Fisher and Paykel M 850/heat and moisture exchanger[HME] filter) was used for all patients whenever available. Uncuffed endotracheal tubes were used in infants and cuffed tubes in older children. Continuous mainstream EtCO2 monitoring probe, IRMA MAXIMO gas analyzer was attached to the endotracheal tube end for recording the EtCO2.[3] Capnography and EtCO2 values were obtained using a multiparameter monitor (Truscope II; 12” Multi-parameter Monitor, Schiller).

Demographic data like age, sex, socioeconomic status were recorded. Anthropometric details were obtained. History and physical findings of each patient were recorded with relevant investigations at the time of admission and progress throughout ICU stay. The disease of the patient, major organ systems involved, indication for ICU admission, and that of mechanical ventilation were noted. The patients were resuscitated by the ICU team and managed as per ICU protocols. Hemodynamic instability was defined as perfusion failure represented by clinical features of circulatory shock and advanced heart failure.[4] In the present study, hemodynamic stability was based on the measurement of vital signs irrespective of the use of vasopressor and ventilatory support. When the baby was hemodynamically stable on the ventilator, ABG was done, and simultaneously EtCO2 values were noted. The mode of ventilation, humidification used, oxygenation, and ventilator parameters were recorded at each measurement of ABG. Due to the risk of an increase in dead space in infants and young children with the use of HME filter, it was used only in older children and adolescents.[5] A maximum of five ABGs (minimum one ABG) was taken for each patient at an interval of at least 12 hours ensuring stable hemodynamic state. Oxygenation parameters were fractional inspired oxygen concentration (FiO2), PaO2, PF ratio, and oxygenation index (OI). PF ratio was calculated using the formula PaO2/FiO2, and OI was calculated using the formula (FiO2 × MAP [mean airway pressure])/PaO2. Ventilation parameters were respiratory rate (RR), peak inspiratory pressure (PIP), positive end-expiratory pressure (PEEP), tidal volume (Tv), and ventilation index (VI). VI is a calculation used to determine the severity of respiratory illness (acute lung injury and/or respiratory distress syndrome) in critically ill patients. It was calculated in pressure mode of ventilation using the formula [RR × (PIP − PEEP) × PaCO2]/1,000, whereas RR is the input ventilator respiratory rate.[6]

Laboratory procedures: For ABG analysis, 0.1 mL of arterial blood was collected from radial artery puncture using 1-mL heparinized syringe (flushed with 20 IU/mL heparin solution) and analysis was done within 15 minutes of collection using Instrumentation Laboratory Worldwide (GEM Premier 3000) or Eschweiler Gas analyzer.[7] [8]



The outcome variable was EtCO2, arterial PaCO2, PF ratio, OI, and VI.



Sample Size

Assuming a confidence level 1 − α(α) of 95%, anticipated population proportions (P) of 50% and absolute precision (d) of 8%, the minimum sample size required was computed to be 150. A total of 223 patients were mechanically ventilated during the study period, 160 patients meeting the inclusion criteria were included for the study during hemodynamically stable condition; 535 pairs of ABG and EtCO2 were obtained for analysis.


Statistical Methods

Data were analyzed using IBM SPSS statistics 24. Frequency distributions of variables were computed using the frequency procedure (categorical variable) and descriptive statistics (scale variable). Their association with normal (2–5 mm of Hg) and high gradient (> 5 mm of Hg) was computed using Chi-square test of independence (categorical variable), independent sample “t”-test (scale variable), and Mann Whitney test (when standard deviation [SD] > mean for scale variables). Pearson's bivariate correlation between PaCO2 and EtCO2 was computed to study the linear correlation. Coefficient of determination was computed applying the linear regression procedure with PaCO2 as the dependent and EtCO2 as the independent variable. The cut-off p-value for the test of significance was taken as <0.05.



Out of a total of 646 patients admitted to PICU during the study period, 223 required mechanical ventilation. Three patients with congenital cyanotic heart disease were excluded. A total of 535 recordings of ABG and EtCO2 were obtained from 160 critically ill ventilated patients during the hemodynamically stable condition, with a maximum of five recordings per individual patient.

Out of 160 patients, 85 (53.1%) were infants below 12 months with a male: female ratio of 1.46:1. The mean (SD) age of the study population was 31.15 ± 40.46 months. Weight for age (Z-score) was < − 2 in 76 (47.5%) children. Pneumonia and meningoencephalitis were leading causes for admission constituting 36 (22.5%) and 32 (20%) children, respectively. Respiratory distress and neurological conditions were the leading causes of ventilation in 89 (55.6%) and 60 (37.5%) children, respectively. Median (IQR [interquartile range]) duration of ventilation was 3 (2,5) days ([Table 1]).

Table 1

Baseline characteristics of ventilated children in PICU (n = 160)





95 (59.4%)


65 (40.6%)

Age (mo)

≤ 1 y

85 (53.1%)

>1 y

75 (46.9%)

Weight for age (Z-score)

< −2

76 (47.5%)

−2 to 2

83 (51.9%)


1 (0.6%)

Duration of ventilation[a] (d)

4.33 (4.89)

Duration of ICU stay[a] (d)

7.02 (9.18)

Indication of ICU admission

Respiratory distress

89 (55.6%)

Respiratory failure

3 (1.9%)


60 (37.5%)


8 (5%)



36 (22.5%)


32 (20%)


19 (11.9%)

Severe malaria

12 (7.5%)

CAHD and

24 (15.0%)


37 (23.1%)


Abbreviations: CAHD, congenital acyanotic heart disease; GCS, Glasgow coma scale; ICU, intensive care unit; PICU, pediatric intensive care unit.

a Mean (SD).

[Table 2] shows the EtCO2 recording of ventilated children in PICU. SIMV (PC or pressure control + PS or pressure support) was the most common mode of ventilation during 327 (61.1%) recordings, and servo-controlled heated wire humidification was used during 357 (66.7%) recordings. EtCO2 and PaCO2 differences were normal (2–5 mm of Hg) in 393 (73.4%) pairs in the present study with a mean difference of 6.71 ± 10.14 mm of Hg. EtCO2 was higher than PaCO2 in 100 (78.8%) patients with pneumonia.

Table 2

End-tidal carbon dioxide recording of ventilated children in PICU (n = 535)



Mode of ventilation


327 (61.1)


193 (36.1)


15 (2.8)


Heated wire (Active)

357 (66.7)


84 (15.7)


94 (17.6)

End-tidal CO2 [a] (mm Hg)

46.17 (13.87)

End-tidal CO2 [b] (mm Hg)

44 (36,54)

EtCO2 > PaCO2 (n = 482)

Patient with pneumonia

100 (78.8%)

Patient without pneumonia

382 (93.6%)

EtCO2–PaCO2 difference (mm Hg)

Normal (2–5)

393 (73.5)

High (>5 mm)

142 (26.5)

EtCO2–PaCO2 difference[a] (mm Hg)

6.71 (10.14)

EtCO2–PaCO2 difference[b] (mm Hg)

4 (2,6)

Abbreviations: HME, heat moisture exchanger; IQR, interquartile range; PC, pressure control; PICU, PICU, pediatric intensive care unit; PS, pressure support; SD, standard deviation; SIMV, synchronized intermittent mandatory ventilation; VC, volume control.

a Mean (SD).

b Median (IQR).

[Table 3] shows the factors affecting high PaCO2–EtCO2 gradient (>5 mm of Hg). Critically ill children with lower mean weight, prolonged ventilation, pneumonia, high PaCO2, and high VI have a higher likelihood of having a high gradient. No significant difference was found with age, sex, humidification types, pH, and OI.

Table 3

Factors affecting arterial end-tidal carbon dioxide gradient in ventilated children in PICU


Normal gradient

n = 393

High gradient

n = 142







Age[b] (mo)

11 (4,42)

8.5 (4,27)


Duration of ventilation[a] (d)

5.07 ± 4.84

6.26 ± 5.80


Duration of ICU stay[a] (d)

7.82 ± 9.34

10.09 ± 11.32


Disease condition


73 (18.6)

20 (14.1)



73 (18.6)

54 (38)

CAHD with pneumonia

62 (15.8)

14 (9.9)


47 (12.0)

20 (14.1)

Severe malaria

8 (2.0)

1 (0.7)


130 (33.1)

33 (23.2)

Mode of ventilation


228 (58.0)

99 (69.7)



157 (39.9)

36 (25.4)


8 (2.0)

7 (4.9)

Humidification types


264 (67.2)

93 (65.5)



55 (14.0)

29 (20.4)


74 (18.8)

20 (14.1)

Acid base status


7.40 ± 0.09

7.38 ± 0.18


HCO3 (meq/L)[a]

24.63 ± 5.64

27.64 ± 8.93


TCO2 [a]

27.00 ± 20.83

27.39 ± 18.45


Oxygenation parameters

PaO2 [a] (mm of Hg)

152.90 ± 77.46

146.36 ± 89.51


FiO2 [a] (%)

82.02 ± 19.79

77.01 ± 22.30


SpO2 [a] (%)

97.22 ± 2.51

97.77 ± 2.29


AaDO2 [a] (mm of Hg)

256.44 ± 157.31

248.7 ± 167.38



46.60 ± 28.37

45.48 ± 33.84


PF ratio[a]

201.85 ± 133.73

212.10 ± 148.37


Ventilatory parameters

PaCO2 (mm of Hg)[a]

41.46 ± 10.87

48.57 ± 26.88


FiCO2 [a] (%)

3.61 ± 0.73

3.99 ± 1.42


Respiratory rate[a]

26.35 ± 5.48

29.79 ± 5.01


PIP (n = 235, normal,104 high)[a]

17.48 ± 3.00

16.86 ± 3.77


Tv (n = 158 Normal, 38 high)[a]

8.16 ± 1.36

8.38 ± 1.42



5.48 ± 0.92

5.25 ± 1.16


VI (n = 235 normal, 104 high)[a]

15.95 ± 6.32

19.42 ± 15.14


Abbreviations: AaDO2, alveolar arterial oxygen gradient; CAHD, congenital acyanotic heart disease; HME, heat and moisture exchanger; IQR, interquartile range; OI, OI, oxygenation index; PC, pressure control; PEEP, positive end expiratory pressure; PF, PaO2/FiO2; PICU, pediatric intensive care unit; PIP, peak inspiratory pressure; PS, pressure support; SD, standard deviation; SIMV, synchronized intermittent mandatory ventilation; Tv, tidal volume; SD, standard deviation; VC, volume control; VI, ventilation index.

a Mean (SD).

b Median (IQR).

c Mann-Whitney test.

Note: Bold values represent significant data.

[Table 4] and [Fig. 1] compare the correlation of EtCO2 with PaCO2. EtCO2 had a strong positive correlation with PaCO2 (r = 0.723, 95%CI [confidence interval] = 0.68–0.76). A subgroup analysis was done with different oxygenation parameters and ventilation parameters to find out any variations in the correlation between EtCO2 and PaCO2. Correlation is minimally affected by oxygenation parameters, i.e., PF ratio or OI. At PF ratio <200 and OI >25 we found a strong correlation between EtCO2 and PaCO2 (r = 0.697, 95% CI = 0.63–0.74 and r = 0.721, 95% CI = 0.67–0.77, respectively). However, presence of pneumonia and high ventilation index (VI >20) adversely affected the relationship with poor correlation coefficient (r = 0.449, 95% CI = 0.30, 0.58 and r = 0.227, 95% CI = 0.03, 0.41, respectively) ([Table 4]; [Figs. 2] and [3]).

Table 4

Correlation between EtCO2 and PaCO2 in the study population

No. of pairs

PaCO2 [a]

EtCO2 [a]

Correlation coefficient

95% CI

Coefficient of determination

Total no of Pairs (n = 535)

43.35 (16.95)

46.17 (13.87)




Children with pneumonia (n = 127)

49.43 (21.78)

50.99 (16.01)




Children without pneumonia (n = 408)

41.5 (14.7)

44.7 (12.8)




PF ratio >200 (n = 214)

41.09 (14.81)

44.75 (12.85)




PF ratio ≤ 200 (n = 321)

44.85 (18.10)

47.12 (14.44)




OI >25 (n = 405)

44.16 (17.20)

46.58 (13.89)




OI ≤ 25 (n = 130)

40.83 (15.92)

44.92 (13.80)




VI >20 (n = 95)

62.61 (17.62)

60.31 (13.90)




VI ≤ 20 (n = 244)

37.35 (11.28)

42.88 (12.19)




Abbreviations: CI, confidence interval; OI, oxygenation index; PF, PaO2/FiO2; SD, standard deviation; VI, ventilation index.

a Mean (SD).

b Significant at 0.05 level.

c Significant at 0.01 level.

Zoom Image
Fig. 1 Bland Altman plot in infants and children (EtCO2 PaCO2 pairs 535).
Zoom Image
Fig. 2 Correlation of EtCO2 and PaCO2 in relation to VI. VI, ventilation index.
Zoom Image
Fig. 3 Correlation of EtCO2 and PaCO2 in relation to OI. OI, oxygenation index.



In the present study, we have evaluated the relationship of EtCO2 with PaCO2 in critically sick ventilated infants and children. We found the EtCO2 had a strong positive correlation with PaCO2, and it provides a clinically relevant and valid estimation of ventilation in critically sick ventilated children. In patients with high ventilation index (VI > 20) and pneumonia, it showed a correlation coefficient of 0.227 and 0.449, respectively, and R 2 is suggestive of only 5 to 20% variation in PaCO2 that could be explained by EtCO2.

Bohr equation states that physiological dead space ventilation (VD) is equal to Tv multiplied by PaCO2 minus partial pressure of expired carbon dioxide (PeCO2) divided by PaCO2.[9] As the VD is directly related to the gradient, the weak correlation of EtCO2 and PaCO2 in the present study may be explained by the increase in the physiological dead space in critically sick children with a different lung condition which might be driving the gradient between EtCO2 and PaCO2.

In a prospective study in children with traumatic brain injury, Yang et al analyzed agreement between arterial carbon dioxide levels with EtCO2 levels (the agreement was defined as PaCO2–EtCO2 gradient between 0 and 5 mm Hg). There was 42% agreement, and on average, PaCO2 was 2.7 mm Hg (95% limits of agreement, –11.3 to 16.7) higher than EtCO2. Low PaCO2–EtCO2 agreement was seen in patients with acute respiratory distress syndrome (ARDS). However, in the present study, the PaCO2–EtCO2 gradient was reported to be normal in 73.4% of children. We found poor correlation coefficient (r = 0.449, 95% CI = 0.30, 0.58) in the children with pneumonia in agreement with the study by Yang et al.[10]

Mehta et al studied the predictive capability of EtCO2 in sick ventilated infant and children and found PaCO2 having an excellent correlation with EtCO2 (n = 96, r = 0.914), similar to our study. They found the PF ratio < 200 adversely affected relationship with a correlation coefficient of 0.83 similar to our result. However, Mehta et al found a good correlation at high VI in contrary to our findings, which might be due to small sample size in their study compared with our study (15 vs. 95 pairs).[11]

Meredith and Monaco and McDonald et al also found a strong positive correlation (n = 1,708, r = 0.716), and (n = 132, r = 0.79) and a negative impact of severe lung disease, similar to our study. However, both the studies had drawn an average of 17 and eight pairs per patient, respectively, whereas we drew up to five pairs per patient to maintain better validity of coefficient of correlation.[12] [13] Previous studies by Hopper et al and McDonald et al also found the influence of VI and PF ratio on the PaCO2–EtCO2 relationship similar to our study.[13] [14] Similarly, McDonald et al reported the PaCO2–EtCO2 gradient to be higher with increasing duration of mechanical ventilation. However, in contrary to our findings, their study found more percentage of the high gradient (> 10 mm of Hg) in children with PF ratio of < 200 compared with that of > 200 (35 vs. 10%). We found an insignificant difference in PF ratio in both normal and high gradient group.[13]

Sidestream distal EtCO2 was measured by a microstream capnograph via the extra port of a double-lumen endotracheal tube by Kugelman et al in 27 ventilated neonates with 222 measurements and found a good correlation and agreement between PaCO2 and mainstream proximal EtCO2. However, our study using proximal mainstream EtCO2 excluded neonates. Further studies comparing neonate and older children with proximal and distal EtCO2 recording are required to validate these results.[15]

Goonasekera et al reported EtCO2 values to be higher than PaCO2 in 22.7% of the observation in ventilated children. Similarly, we found EtCO2 values to be higher than PaCO2 in 105 (19.6%) children. The PaCO2–EtCO2 difference correlated positively with the alveolar-arterial oxygen tension or pressure difference (AaDO2) difference (ρ = 0.381 p < 0.0001). We have not studied the correlation of PaCO2–EtCO2 difference with AaDO2, but we observed no statistically significant difference in AaDO2 in both normal and high gradient group (p = 0.622).[16]

McSwain et al monitored mechanically ventilated children using volumetric capnography and compared the EtCO2–PaCO2 correlation in different ranges of physiological dead space to tidal volume ratio (Vd/Vt). The correlation coefficient between EtCO2 and PaCO2 ranges from 0.78 to 0.95. The EtCO2–PaCO2 gradient increased predictably with increasing Vd/Vt. We found a correlation coefficient of 0.723 in our cohort; the low correlation in our study could be due to higher prevalence of severe lung disease (pneumonia and ARDS) with high Vd/Vt.[17]

There are several limitations to our study. The study was conducted at a single center in a limited resource PICU with most children admitted with pneumonia and/or respiratory failure. Studies with different etiologies in multiple centers need to be conducted to validate the results. Only mainstream capnometer was used. However, previous studies comparing both mainstream and sidestream capnometer reveal similar results and can be extrapolated to include both types. Several factors affecting the EtCO2 and PaCO2 gradient may be confounding to each other, and a regression analysis could give better results. All efforts have been taken to take the reading at stable hemodynamic state; however, some reading might have been taken in unstable condition confounding the results. Again, capnography, the graphical representation though very useful for an individual patient, it could not be used for analysis and deriving statistical inference.



In hemodynamically stable yet critically ill ventilated children, continuous noninvasive monitoring of ventilation, i.e., EtCO2 correlates strongly with the gold standard monitoring, i.e., PaCO2, obviating the need for repeated ABG in resource-poor settings. This emphasizes the practice of EtCO2 use in PICU. EtCO2 showed good validity to predict PaCO2 and not much affected by oxygenation parameters. The correlation was greatly affected by the presence of pneumonia and high ventilation index; hence it is recommended to monitor PaCO2 invasively in these patients until a good correlation is established.


Conflict of Interest



We thank Prof. Leena Das for constantly inspiring us in this work; Dr. Bijaya Bhusan Nanda, Deputy Director, Regional Institute of Planning, Applied Economics and Statistics, Odisha, for providing statistical guidance; Francis Satapathy for his help in drafting the manuscript.

Authors' Contributions

B.K.M. conceived and designed the study, analyzed the data, revised the article, and act as the guarantor of the study. A.K. and D.D.P. collected the data and drafted the paper. A.K. and S.K.S. analyzed the data and revised the article. All the authors approved the final manuscript.

Address for correspondence

Bijay Kumar Meher, MD
Bhima Bhoi Medical College and Hospital
C/455, Sec-6, CDA, Cuttack 753014, Odisha

Publication History

Received: 07 April 2020

Accepted: 07 June 2020

Publication Date:
20 August 2020 (online)

© 2020. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (

Georg Thieme Verlag KG
Stuttgart · New York

Zoom Image
Fig. 1 Bland Altman plot in infants and children (EtCO2 PaCO2 pairs 535).
Zoom Image
Fig. 2 Correlation of EtCO2 and PaCO2 in relation to VI. VI, ventilation index.
Zoom Image
Fig. 3 Correlation of EtCO2 and PaCO2 in relation to OI. OI, oxygenation index.