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Abstract
Objectives To compare the agreement, precision and repeatability of end tidal carbon dioxide (
) and transcutaneous carbon dioxide (
) with partial pressure of arterial CO2 (
) in postoperative neonates.
Patients Fifty mechanically ventilated neonates without lung disease, and with no contraindications for either 
or 
monitoring.
Interventions Paired 
and 
values were recorded with three consecutive 
measurements within the first 48 h of surgery.
Main outcome measures 
, 
and 
triplets were compared using Bland-Altman plots.
Results One hundred thirty-two triplet measures of CO2 were recorded with mean 
43.5 (7.3) mm Hg, 
38.8 (6.4) mm Hg and 
43.8 (8.8) mm Hg (p<0.0001 for 
against 
; paired t test). The 
−
bias±2SD was 4.1±9.0 mm Hg and −0.8±13.0 mm Hg for 
−
. 56.1% of 
, and 60.6% of 
values were within ±5 mm Hg of paired 
.
Conclusions In postoperative neonates, 
and 
demonstrated a clinically acceptable agreement with 
.
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What is already known on this topic
-
Transcutaneous carbon dioxide (
) is widely used to monitor partial pressure of arterial CO2 () trends in the neonatal intensive care unit (NICU) but rarely during or after surgical procedures. -
End tidal carbon dioxide (
) monitoring is an accepted and reliable method of indicating in the anaesthetised patient. -
is rarely used in the NICU due to variable accuracy in preterm neonates and neonates with severe respiratory failure.
What this study adds
-
Transcutaneous carbon dioxide (
) demonstrated good agreement with partial pressure of arterial CO2 () in postsurgical neonates without lung disease, but lacked precision over time. -
End tidal carbon dioxide (
) underestimated by about 4 mm Hg but demonstrated better precision than . -
This study suggests that both
and are feasible methods of tracking trends over time in the postsurgical neonate.
Introduction
Non-invasive monitoring carbon dioxide (CO2) is frequently advocated in the care of the ventilated neonate.1 Transcutaneous CO2 (
) monitoring and end tidal CO2 (
) are the two most commonly used techniques. Although 
monitoring is a standard of care during anaesthesia,2 the use in infants is limited due to conflicting results regarding accuracy.3–7 In contrast, 
is known to provide a good agreement with partial pressure of arterial CO2 (
)4 and accurately trend over time.4 Consequently, 
monitoring is used more in the neonatal intensive care unit (NICU) environment than 
, although neither has gained universal acceptance, mainly due to technical limitations.
Previous studies of side-stream 
identified a clinically unacceptable underestimation of 
.4 ,6 ,7 These studies predominantly involved preterm neonates with lung disease. 
sensors cannot identify an alveolar CO2 plateau in the large ventilation-perfusion mismatching and fast rate, small tidal volume states characteristic of this population.1 ,2 Neonates are also ventilated after surgery, often without lung disease, and also need strict control of the postoperative course to minimise long-term morbidity. No study has specifically investigated continuous CO2 monitoring in the surgical neonate despite the suitability of this population to non-invasive techniques.
The aim of this study was to compare the agreement, precision and repeatability of sidestream 
and 
with 
in mechanically ventilated postoperative neonates without lung disease.
Methods
This study was performed at the Royal Children's Hospital (Melbourne, Australia), a regional surgical NICU, and approved by our research ethics committee. Mechanically ventilated neonates, without primary respiratory failure, <12 h postoperative were studied if they had an indwelling arterial line. Neonates with clinical states known to limit the accuracy of either device were not studied, including congenital diaphragmatic hernia and cyanotic heart disease, fragile skin, significant shock, hypotension, metabolic acidosis, inotropes likely to significantly impair skin perfusion or endotracheal tube leak >20%. Mechanical ventilation was applied using either synchronised intermittent mandatory ventilation or synchronised intermittent positive pressure ventilation with or without volume-targeted modes at the discretion of the clinical team.
On completion of surgery, a microstream FilterLine neonatal sidestream 
system (Oridion Medical Inc., Needham, Massachusetts, USA; deadspace <0.5 ml, sampling rate 50 ml/min) was incorporated into the ventilator circuit distal to the flow sensor. A 
probe (TINA, Radiometer Medical, Brønshøj, Denmark) was secured to the abdomen or chest, preferably the right upper chest. The sensor was allowed at least 20-min to achieve thermostability at 43°C before arterial sampling, and repositioned at least 4 hourly. This system does not allow manual calibration to 
. The capnographic waveform and numerical values for 
and 
were displayed with the arterial pressure waveform in real-time (MP70 monitor, Philips Medical, Boeblingen, Germany). Clinicians were not blinded to either measure and were allowed to make ventilation changes based on the displayed 
values. Arterial blood gas samples were taken when clinically indicated. The results were recorded and the alveolar to arterial oxygen tension (A/a) ratio (Partial pressure of alveolar oxygen 
; where 0.8=respiratory quotient) calculated. Severe lung disease was defined as an A/a ratio<0.3.
At the time of blood gas analysis, the highest 
and 
during the 10 consecutive inflations immediately before and after arterial sampling were recorded. Only 
values with a distinct alveolar plateau on the capnographic waveform were included. This was repeated for three consecutive arterial samples unless the arterial line was removed, extubation or ineligibility criteria occurred.
Statistical analysis
The Bland-Altman technique8 was used to determine 
−
and 
−
agreement. Limits of agreement (precision) defined as two SDs of the bias. A bias of ±5 (10) mm Hg was deemed clinically acceptable.4 ,5 Subgroup analysis to determine the influence of tidal volume, 
site, time since 
re-position and order of arterial sampling was made.
Results
Fifty neonates were studied and summarised in table 1. A total of 132 arterial blood gases (56% postductal) were performed, 45 neonates had two or more measurements with 37 neonates having three. The sensor site or duration since re-position did not influence the 
results.
Subject characteristics
The respective mean (SD) 
, 
and 
values were 43.6 (7.0) mm Hg, 39.4 (6.3) mm Hg and 44.3 (8.8) mm Hg, with 
being lower than 
and 
(both p<0.0001, paired t test). Overall, 
underestimated 
, with a 
−
bias (2SD) of 4.1 (9.0) mm Hg (figure 1A). 
approximated 
but with wider limits of agreement: bias (2SD) −0.8 (13) mm Hg (figure 1B). These biases were independent of
. 56.1% of 
values, and 60.6% of 
were within ±5 mm Hg of the paired 
(p=0.533, Fisher's exact test). Only 27.3% and 35.6% of 
and 
values were within ±2 mm Hg of 
(p=0.420).
Bland-Altman plots of the difference between partial pressure of arterial carbon dioxide (
) and end tidal carbon dioxide (
) (A) and transcutaneous carbon dioxide (
) (B) against average CO2. Values obtained at the first arterial blood gas are shown with closed circle, second with diamonds and third with open circles. The solid line represents the overall bias with ±2 SD being shown in the dashed lines. The 
−
bias was 4.1 mm Hg and 
−
bias −0.8 mm Hg.
Subgroup analysis found that tidal volumes ≥10 ml, or ≥4.5 ml/kg (table 2), and sampling order resulted in better agreement between both 
and 
with 
(table 3).
Relationship between CO2 measurements and expiratory tidal volume (VT).
Bias (limits of agreement) of CO2 measurements at each arterial blood gas sample
Discussion
The benefit of continuous CO2 monitoring in ventilated neonates is well established,1 but not universally applied. This study suggests that both 
and sidestream 
are reliable methods to describe 
trends in the postoperative period. To our knowledge, this is the largest comparative study of non-invasive CO2 monitoring in ventilated neonates, and the first to selectively identify a population in which neither 
nor 
has significant technical disadvantages.
It is not surprising that there was less discrepancy between 
and 
than 
,4 ,6 
is known to be a reliable proxy of 
in neonates.4 ,7 ,9 The precision of 
, however, was variable, as is evident by the wide limits of agreement. The explanation for this is unclear but likely related to the 
system rather than sensor placement1 application temperature10 and skin perfusion.
underestimated 
compared with 
. Previous studies in neonates found 
underestimated 
by 6.8–11.2 mm Hg.4–7 The better agreement found in our study likely reflects study populations as previous studies included infants with lung disease. 
is known to be more accurate in infants with an A/a ratio >0.3.3 We intentionally choose to limit our investigation, and interpretation, to surgical neonates without lung disease. We found that a sidestream 
system, designed for small volume states, showed better precision between the three sample epochs than
. The intrasubject repeatability of the 
−
bias over these samples suggests that monitoring CO2 trends would be feasible using 
in this population.
The improved agreement between 
and 
at higher tidal volumes illustrates the importance of achieving true capnographic alveolar plateau.2 The relatively large circuit deadspace, high rates and low tidal volumes characteristic of neonatal ventilation may not result in the sampled gas representing true 
.1 ,2 In neonates requiring low tidal volumes 
maybe a better alternative. By contrast, the surgical neonate provides some unique challenges that may limit 
monitoring, including wound dressings, drapes, drains and other monitoring devices limiting access to well perfused 
sites. As neither 
nor 
were clearly superior in this study, our results suggest that the consideration of each system's limitations, and the clinical environment, will be important in determining the most appropriate method of CO2 monitoring for an individual neonate.
Limitations
To minimise unnecessary blood loss the timing of arterial sampling was not standardised. Ventilation strategy were also at the discretion of the treating clinician. Not every neonate contributed three arterial gases. This was a pragmatic choice to represent clinical practice but potentially introduces bias, and may explain the 
differences over time. We contend that the fact that 
agreement did not differ between samples suggests that the 
differences were related to other factors. Overall, the postsurgical population is a significant contributor to NICU occupancy, but specific diagnoses are rare and this resulted in a heterogeneous population, limiting subgroup analysis.
Conclusion
In postsurgical neonates without lung disease, 
underestimated 
more than 
but provided greater precision over repeated arterial blood gases, however it was less accurate at smaller tidal volumes. Both techniques are feasible methods of non-invasively monitoring CO2 trends in the postsurgical neonate. The clinician should be aware of the specific advantages and disadvantages of each.
Acknowledgments
The authors wish to thank Dr Neil Patel for assistance in preparing this manuscript.
References
Footnotes
-
Contributors All authors made substantial contributions to conception and design, data acquisition, analysis and interpretation. All authors were involved in the drafting of the submitted manuscript and approve of the manuscript in current form. DGT authored the first draft of the manuscript.
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Financial support DGT is supported by a National Health and Medical Research Council Clinical Research Fellowship (Grant ID 491286) and the Victorian Government Operational Infrastructure Support Programme.
-
Competing interests None.
-
Ethics approval Human Research Ethics Committee of the Royal Children's Hospital, Melbourne, Victoria, Australia.
-
Provenance and peer review Not commissioned; externally peer reviewed.