Objectives To determine the feasibility of end tidal (EtCO2) monitoring of preterm infants in the delivery room, to determine EtCO2 levels during delivery room stabilisation, and to examine the incidence of normocapnia (5–8 kPa) on admission to the neonatal intensive care unit in the EtCO2 monitored group compared with a historical cohort without EtCO2 monitoring.
Patients and methods Preterm infants (<32 weeks) were eligible for inclusion in this observational study. The evolution of EtCO2 values immediately after delivery was assessed and linear least-squares methods were used to fit a line to EtCO2 recordings. The partial pressure of CO2 in blood (PCO2) from the infants who received EtCO2 monitoring was compared with a historical cohort without EtCO2 monitoring.
Results EtCO2 monitoring was feasible in the delivery room. EtCO2 values were successfully obtained in 39 (88.7%) of the 44 infants included in the study. EtCO2 gradually increased over the first 4 min. Intubated infants had higher EtCO2 values compared with infants who were not intubated, with median (IQR) values of 4.7 (3.3–8.4) kPa versus 3.2 (2.6–4.2) kPa (p=0.05). No difference was found between the proportions of PCO2 values within the range of normocapnia among infants who received EtCO2 monitoring compared with those who did not (56.8% vs 47.9%, p=0.396).
Conclusions Delivery room EtCO2 monitoring is feasible and safe. EtCO2 values obtained after birth reflect the establishment of functional residual capacity and effective ventilation. The potential short-term and long-term consequences of EtCO2 monitoring should be established in randomised controlled trials.
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What is already known on this topic
End tidal carbon dioxide (EtCO2) can be used to monitor infants in the neonatal intensive care unit.
Little is known about EtCO2 levels immediately after birth in preterm infants.
What this study adds
EtCO2 monitoring of preterm infants in the delivery room is feasible.
EtCO2 levels are low at birth and increase over the first few minutes of life.
EtCO2 levels were higher in infants who required intubation compared with infants that did not.
Oxygen saturation (SpO2) and heart rate monitoring are routinely used to assess transition immediately after birth.1 Many preterm infants (<32 weeks) need assistance to ensure that this adaptive process is completed effectively.2 The Neonatal Resuscitation Program advises positive pressure ventilation (PPV) if the infant is apnoeic or has a heart rate of <100 bpm.1 Continuous positive airway pressure should be provided if a preterm infant has laboured respirations, is cyanotic, or has low SpO2 levels despite having a heart rate of >100 bpm during this stabilisation period.
Carbon dioxide (CO2) monitoring in the neonatal intensive care unit (NICU) setting may help to avoid hypocapnia, which may contribute to lung injury3 as well as periventricular leukomalacia (PVL),4 ,5 or hypercapnia, which may contribute to an increase in the risk of intraventricular haemorrhage.6 ,7 However, CO2 monitoring during the stabilisation process in the delivery room is not well studied.8–11 End tidal CO2 (EtCO2) levels have been shown to initially rise and subsequently plateau within the first few minutes of life.8 ,12 Thus, EtCO2 monitoring may be an early indication of lung expansion and may help to guide successful respiratory support in the delivery room.11 ,13
The aims of our study were to (1) investigate the use of capnography as a means of measuring EtCO2 levels in preterm infants in the delivery room, (2) to determine EtCO2 levels in intubated and non-intubated preterm infants during the first 10 min of age, and (3) to examine the short-term outcomes of preterm infants who had EtCO2 monitoring in the delivery room compared with those who did not.
This was an observational study conducted in the delivery room of Cork University Maternity Hospital from April 2013 through May 2014. Any infant <32 weeks’ gestation was eligible for inclusion. Exclusion criteria included oligohydramnios (amniotic fluid index <5) and any expected congenital anomalies.
A Microstream CO2 Filterline sidestream capnography device attached to a Philips Intellivue monitor (both Philips Healthcare, Massachusetts, USA) was used to provide EtCO2 measurements. This device has a dead space volume of <0.5 mL. The medical team was instructed to obtain capnographic waveforms, but not to make adjustments based on the capnometry values displayed. All personnel were familiar with the system and had undergone a training session on the provision of PPV with the capnography system.
The default settings on the T-Piece resuscitator were set at a gas flow of 8 L/min, a peak inspiratory pressure (PIP) of 20 cm H2O, and a positive end expiratory pressure (PEEP) of 5 cm H2O. The maximum attainable PIP was limited to 30 cm H2O, as is routine for all preterm deliveries at our centre. Once an infant was placed on the resuscitation table, EtCO2 monitoring commenced and continued throughout the stabilisation process. The entire monitoring period was also recorded on digital video. Afterwards, a member of the research team downloaded the EtCO2 values from the Intellivue monitor in 12 s data intervals using the ‘review’ function. These data were then matched, by authors GAH and EMD, to the video recording of the infant.
The median andinterquartile range (IQR) was used to summarise EtCO2 values obtained over the first 10 min. We also assessed features related to the linear increase of EtCO2 using the linear least-squares method to fit a line to the first 4 min of recording. This representation of EtCO2 immediately after birth was used because of the variability of the data during that period, the relative stabilisation of EtCO2 production thereafter, and the explorative nature of this study. From this line, we calculated slope, intercept and IQR about the line and used these features to summarise the time-varying nature of EtCO2. Unless stated otherwise, we report all values as ‘median (IQR)’.
We used the area under the operating characteristic curve (AUC) as a measure of effect size. We generated a 95% CI for the AUC using a bootstrap approach with 1000 iterations.14 In addition to the effect size measure, we applied the Mann–Whitney U test to the data with the value p<0.01 indicating statistical significance, adjusted using a Bonferroni approach for the five comparisons. We performed this analysis in Matlab (V.R2013a, The MathWorks, Natick, Massachusetts, USA).
The partial pressure of CO2 in blood (PCO2) was obtained <1 h from birth and was compared with a historic cohort of infants recruited for a blood sampling study who also had PCO2 analysis completed within 1 h of birth (December 2012–April 2013). These infants did not receive EtCO2 monitoring in the delivery room. Initial PCO2 readings were considered within the range of normocapnia if they fell between 5 and 8 kPa. Both studies had the same inclusion and exclusion criteria and there was no change in overall resuscitation training or practice during the timeline of either of these studies. Statistical analysis for the comparisons of PCO2 values between the groups was performed using SPSS V.21.0 (IBM, New York, USA). Comparative tests of medians were completed using Mann–Whitney U tests and a p<0.05 was deemed as being statistically significant. Comparative tests on the number of infants falling within the target range, the number of infants who were intubated, and the male/female distribution were completed using Fisher's exact tests and a p<0.05 was deemed as being statistically significant. Cross-tabulation determining the effect of blood gas type on whether or not infants fell within the accepted range were completed using a Cramer's V test with a p<0.05 deemed as being statistically significant.
Fifty-nine patients were consented antenatally. This was a convenience sample. Eleven patients subsequently delivered beyond 32 weeks’ gestation, and in four cases, a member of the research team was unavailable; therefore, 44 infants were included. All mothers of these infants received at least one dose of antenatal steroids prior to delivery. Of the 44 infants included, 11 received PEEP and PPV but were subsequently intubated in the delivery room because of ongoing respiratory distress. Of the 33 non-intubated infants, PEEP and PPV were provided to 11, and PEEP alone was provided to 22. Operator error in connecting the capnography sampling line to the portable monitor occurred in three resuscitations; data retrieval from the monitor was unsuccessful after two resuscitations, thus 39 (88.6%) infants had EtCO2 readings suitable for analysis.
EtCO2 levels initially increased linearly, and subsequently plateaued in infants who were intubated (n=10) and in those who received only facemask ventilation (n=29) (figure 1). Intubation occurred within 4 min of age. No difference in the level of linear EtCO2 increase was found between intubated and non-intubated infants (line slope of 0.41 (0.00–0.85) kPa/min vs 0.24 (0.03–0.54) kPa/min, p=0.417) (figure 2). A significant difference was seen between groups for EtCO2 line IQR (p=0.008) (table 1). Overall, intubated infants had a median EtCO2 value of 4.7 (3.3–8.4) kPa and non-intubated infants had a median EtCO2 value of 3.2 (2.6–4.2) kPa (p=0.05) (figure 2). Non-intubated infants had an EtCO2 line intercept value of 2.3 (1.5–3.5) kPa that increased to between 3 and 4 kPa within the initial minutes after birth (figure 1). The EtCO2 line intercept value was 1.9 (1.0–3.7) kPa and subsequently increased >6 kPa (figure 1) in intubated infants.
Short-term outcome comparison
Forty-eight infants with a median gestational age of 29 (+1/7) were recruited in the historic cohort of whom 47.9% had an acceptable PCO2 reading within 1 h of birth compared with 56.8% in the monitored group (p=0.396) (table 2). There was no difference in the blood gas sampling methods performed in both the monitored group and the non-monitored group.
We have documented the evolution of EtCO2 in a cohort of preterm infants over the first 10 min of age. We think our finding of an initial very low value that increased over the next few minutes is consistent with increased alveolar gas exchange as lung recruitment and increasing gas exchange surface area occurs. Hooper et al12 highlighted an increase in EtCO2 values over the first few minutes of adaptation in an animal model and a cohort of 10 preterm infants. Our study highlights a similar trend in EtCO2 values, but in a larger number of preterm infants. Kong et al8 alluded to slowly increasing EtCO2 values over the first 3.5 min of age in a cohort of 48 infants. As the aim of that study was to investigate the utility of EtCO2 monitoring in the delivery room, analysis of EtCO2 production was based on the average of the last five breaths of the stabilisation period. In contrast, our study describes the evolution of EtCO2 in the first minutes of life.
We found that EtCO2 values were higher in infants who were subsequently intubated compared with those who were not (4.7 (3.3–4.8) kPa vs 3.2 (2.6–4.2) kPa), although the difference was not significant (p=0.05) after adjusting for multiple comparisons. We also found no statistical difference between the line intercept values (1.9 (1.0–3.7) kPa vs 2.3 (1.5–3.5) kPa, p=0.728) or in the slope of the line (that likely represents the subsequent rate of change in EtCO2 values) in infants who were intubated compared with those who were not.
Although neither the intercept nor the slope of the line showed a difference between the groups, the difference in the line IQR between intubated and non-intubated infants (p=0.008) suggests a possible clinical difference between these groups. The higher values in infants subsequently intubated likely represent ineffective adaptation secondary to underlying lung immaturity, similar to the findings of Kong et al.13 If mask leak or airway obstruction resulted in subsequent intubation, we would have expected lower, not higher, EtCO2 values. EtCO2 monitoring in the delivery room may be a useful tool in confirming effective PPV and may be an early indicator of impaired lung function and respiratory control in preterm infants necessitating further intervention, including intubation. PCO2 levels are only a single endpoint of a complex dynamic process of newborn stabilisation. Investigation of the effect of EtCO2 monitoring on outcome measures, such as SpO2 and heart rate values in the first minutes of life, should be considered in future investigations.
We had postulated that infants receiving EtCO2 monitoring in the delivery room would more likely have PCO2 values in the acceptable range. Although this did not prove to be the case, importantly, the introduction of EtCO2 monitoring did not result in an excess of abnormal CO2 values. Similar to our study, Kong et al8 found no improvement in PCO2 levels in preterm infants receiving EtCO2 monitoring in the delivery room but did note the subjective benefits of having an extra monitoring tool during resuscitation.
As with any new technology that may be introduced into clinical care, it is important that end users receive formal training in the use and interpretation of the technology prior to and following on from its introduction.11 While all our end users had training in a simulation setting, operator error in relation to preparation of the machine occurred in two cases. This highlights the potential importance of human factors in device use. User feedback regarding the use of an EtCO2 monitor in the delivery room was consistent with previous studies.8 ,15
The aim of our study was to assess the role of sidestream capnography in the delivery room alone and was not paired with other readings such as mask leak and tidal volumes. A respiratory function monitor may have provided a better indication of when face mask leak impacted EtCO2 readings. However, our method of matching the capnography monitor data with video recordings allowed us to eliminate most inaccurate readings, although this may not have been the case for all resuscitations. Although there is good correlation between PaCO2 measurements and both mainstream16–20 and sidestream21 ,22 EtCO2 measurements, it is important to note that EtCO2 may not be as accurate in patients receiving facemask ventilation if there is a large leak present. Another limitation of our study is that the initial PCO2 values obtained from both groups of infants within the first hour after birth may have been affected by other clinical interventions in the NICU occurring after immediate stabilisation.
We have shown that the use of capnography is feasible to monitor EtCO2 levels of preterm infants in the delivery room and appears to be safe. EtCO2 levels rise during the initial minutes after birth in all infants. Infants who are subsequently intubated have higher median EtCO2 values. Further research is needed to assess the most effective method of monitoring EtCO2 and its effect on outcomes.
Contributors GAH had primary responsibility for overall manuscript content, study design, data collection, data analysis, data interpretation and manuscript preparation. MK and DF were involved with data collection and data interpretation. JMOT was involved with data analysis, data interpretation and manuscript preparation. KO'H was involved with manuscript content and manuscript preparation. ACR was involved with manuscript design, manuscript content and manuscript preparation. GBB was involved with manuscript content and manuscript preparation. EMD was the supervisor for this study and was involved with overall manuscript content, study design, data collection, data analysis, data interpretation and manuscript preparation.
Funding This study was supported by a Science Foundation Ireland Research Centre Award (INFANT-12/RC/2272). JMOT was supported by a Government of Ireland Fellowship funded by the Irish Research Council (GOIPD/2014/396).
Competing interests None declared.
Patient consent Obtained.
Ethics approval Clinical Research Ethics Committee of the Cork Teaching Hospitals (CREC).
Provenance and peer review Not commissioned; externally peer reviewed.
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