Agreement of Mixed Venous Carbon Dioxide Tension (PvCO₂) and Transcutaneous Carbon Dioxide (PtCO₂) Measurements in Ventilated Infants

Maintenance of normocarbia may reduce the incidence of mortality and morbidity such as intraventricular hemorrhage, periventricular leukomalacia and bronchopulmonary dysplasia in newborns especially premature infants (1, 2). The measurement of blood gas carbon dioxide (CO₂) level is critical tool in the assessment and principal aspect of monitoring the respiratory status specially for neonates, in particular those receiving mechanical ventilation.

Hence acid-base information obtained from blood gas samples taken from an indwelling arterial catheter appears to be the gold standard but it is difficult to obtain a sample and has important complications. Capillary and venous blood gas samplings are easier to obtain and a less invasive way of evaluating acid-base status. Both avoid the risks of arterial punctures. Several studies have shown good correlation between capillary blood, venous blood, and arterial blood gas values (3, 4). Therefore partial venous carbon dioxide tension (PvCO₂) is an alternative to assess the blood carbon dioxide status in sick newborn. Obtaining venous blood sample is invasive and painful method with some complications (infections, significant blood loss). Also it provides only a single measurement of CO₂ tension which is often a rapidly changing parameter (5).

The partial pressure of transcutaneous CO₂ (PtCO₂) is considered as an accurate estimate of both arterial and venous CO₂ tension in infants and children and estimates better than end tidal carbon dioxide (ETCO₂) (5, 6).

The purpose of this study was to compare the PvCO₂ and PtCO₂ data based on separated three PvCO₂ value groups (hypocapnia, normocapnia, and hypercapnia) and to understand the usefulness and limitations of PtCO₂ monitoring in neonatal care.

This prospective and observational study was conducted in the neonatal intensive care unit (NICU) at the Sisli Hamidiye Etfal Educational and Research Hospital, Istanbul during September to December 2012. The local ethics committee approved the study and informal parental consent was obtained for each infant. Inclusion criteria were clinical indication of blood gas sampling and transcutaneous monitoring, and absence of an umbilical or radial arterial catheter. Examination was done within the first 6 to 28 days of life. All measurements were performed on mechanically ventilated infants. Infants were not studied if they were older than 28 days, had anemia, edema, hypotension requiring vasoactive drugs, hypothermia and capillary refill time of greater than two seconds, or if transcutaneous readings could not be made for any reason.

All newborns were monitored by using transcutaneous monitor (TCM TOSCA, Radiometer Medical ApS, Denmark). Once the site was cleaned with soap, 1-2 drops of contact gel was placed inside the ring and sensor fixation ring was placed on upper chest (parasternal anterior chest wall which is a highly vascularized area). The electrode was always placed on the anterior thorax, and its surface temperature was maintained at 44°C, according to manufacturer’s instructions and previous literature. Sensor calibration was automatically done after every monitoring and the membrane was changed every 14 days according to manufacturer's instructions because the electrolytes between the sensor and the membrane became depleted.

Venous blood gas sampling and monitoring of the PtCO₂ level were done simultaneously. Within 5 min the venous blood gas determinations were performed using an automatic blood gas analyzer (Roche Omni C blood gas analyzer, Roche Diagnostic, Diamond diagnostics, USA). At the end of the monitoring, the transcutaneous sensors were removed and the underlying skin examined.

After collection of data, PvCO₂ values were divided into three groups: hypocapnia (Group 1: < 4.68 kPa, normocapnia (Group 2: 4.68–7.33 kPa), hypercapnia (Group 3: >7.33 kPa) and then PvCO₂ and PtCO₂ data within each group were compared separately. The differences between PvCO₂ and PtCO₂ were analyzed using a Student’s paired t test. Agreement was illustrated by Bland-Altman plots with 95% limits of agreement. P-value < 0.05 was accepted to be statistically significant. A bias of more than ± 0.7 kPa was considered unacceptable (7). Data were analyzed and visualized using MedCalc program.

Among the patients included in the study, 9 were term and 26 preterm newborns. The median gestational age was 32 (25-41) weeks, median birth weight was 1700 (780-3400) g and median age at measurement was 13 (6-25) days. Primary diagnoses of infants were prematurity with RDS (n = 19), respiratory failure (n = 11), persistent pulmonary hypertension of the newborn (n = 2), birth asphyxia (n = 2) and pneumothorax (n = 1). A total of 168 measurements of each PvCO₂ and PtCO₂ data were compared in three separated groups (13 readings in hypocapnia group, 118 in normocapnia group, and 37 in hypercapnia group). No infants were excluded due to instability since this was part of the study.

A comparison of PvCO₂ and PtCO₂ levels in kPa according to study groups and gestational weeks (whether term or preterm) of neonates are shown in Table 1. Although a statistical difference was detected, there was clinically a good relation between PvCO₂ and PtCO₂ in preterm, term, Group 1, Group 2 and all infants. On the other hand, only 37.8% of PtCO₂ recordings were within 0.7 kPa of the paired PvCO₂ in hypercapnia group. The difference between PvCO₂ and PtCO₂ (P(v-Tc)CO₂) against average CO₂ in the three Groups are illustrated in Figure 1. PtCO₂ was related to PvCO₂ with laboratory acceptable results between the two measurements in hypocapnia and normocapnia groups. All PtCO₂ values were statistically significant and lower than PvCO₂ data in hypercapnia group (Table 1Figure 1). The mean pH values were 7.37 ± 0.07, 7.32 ± 0.04 and 7.25 ± 0.05 in Groups 1, 2 and 3, respectively. The mean warm-up period was 9.4 ± 0.3 minutes for all patients. No serious skin lesions or any other adverse events were detected except transient mild erythema after 4 (2.3%) measurements.

Figure 1.

Bland-Altman Plot of the Difference Between PvCO₂ and PtCO₂ (P(v-Tc)CO₂) Against Average CO₂

Although PaCO₂ remains the gold standard and PvCO₂ is preferred alternative method, PtCO₂ monitoring is a non-invasive technology and very valuable adjunct for respiratory management and also allows continuous monitoring (5). It is suggested that new generation transcutaneous monitors provide safe and useful carbon dioxide monitoring in newborns (8, 9). In this study close correlation was demonstrated between PvCO₂ and PtCO₂ values in hypocapnic and normocapnic PvCO₂ level whereas for hypercapnic PvCO₂ level was not.

As far as we know, this is the first study to demonstrate the relationship between PvCO₂ and PtCO₂. Several studies have shown a good agreement between PtCO₂ and PaCO₂ in newborn (10-14), although their accuracy diminished when the CO₂ tension increased especially when the increase was greater than 56 mmHg (15, 16). According to our results which are similar to those reports, we cannot assume that the CO₂ variations could reliably reflect PvCO₂ variations in hyperkapnic newborns. Acidosis negatively affects the ability to correlate transcutaneous and venous CO₂ values (5, 13, 17). In hypercapnia group mean pH value was lower than that in the other groups. So, we speculated that the capillary blood flow and gas diffusion of the skin may be even impaired when the pH decreases. This condition impairs the transcutaneous measurements and may alter the PtCO₂ correlation with PvCO₂.

PtCO₂ measurement is based on the observation that CO₂ has a high solubility and diffusion through the skin; local heat dilates blood vessel and enhances skin permeability (18). It is stated that PtCO₂ measurements provide accurate results in newborns because of their thin epidermis. The epidermal layer of preterm infants is advantageous in the accurate measurement of PtCO₂, but on the other hand disadvantages may cause heat induced skin damage (erythema, blisters, burns, skin tears) from the electrodes (19, 20). To achieve accurate measurements, the recommended skin prob temperature is 44°C (9). So transcutaneous CO₂ measurements were carried out at 44°C electrode temperature. According to recommendation for changing sites every 2 hours to avoid thermal injury (9), we monitored the patients no longer than 2 hours and no serious adverse effects were identified except for mild transient erythema after only 2.3% of measurements.

Transcutaneous monitoring systems have some other limitations such as difficulty in keeping them calibrated, preventing air trapping and taking up longer time to sufficiently warming the skin. The need for frequent changes in sensor sites was considered breach of minimal handling approach (21). The response time decreases with elevated electrode temperature (22). In present study we chose high electrode temperature, therefore the calibration problems did not occur in our application. The average time required to heat the skin was found to be 10 minutes. It is a long time, for this reason transcutaneous measurement of carbon dioxide is not useful during the early resuscitation in the delivery room (23). Transcutaneous measurements can be difficult to use in emergency situations and not appropriate to assess the use of instant carbon dioxide level (it requires time to calibrate and warm the skin), but is suitable for follow-up and an important method for monitoring CO₂ in neonates. We had no concern about the minimal handling approach, as the electrode location was not frequently altered. According to our results transcutaneous CO₂ monitoring would not create a serious complication in NICU.

Our study had some limitations; it was a single center study and acceptable limits of agreement of 0.7 kPa was chosen based on previous studies (7). The measurement of PaCO₂ which is considered the gold standard method was not used in our setting because of its practical difficulty. Instead of it we used PvCO₂ which is commonly used paramater in clinical practice.

The present study suggests that the relationship between PvCO₂ and PtCO₂ is deteriorated with hypercapnic level of PvCO₂. When the PvCO₂ levels increase, the difference of PvCO₂ and PtCO₂ values also increase. Transcutaneous PCO₂ measurements have generally good agreement with PvCO₂ in hypocapnic and normocapnic intubated infants but there are some limitations especially for high levels of CO₂ tension. We recommend that transcutaneous readings to be confirmed with blood gas values in order to verify the hypercapnic transcutaneous values and persistent or unexpected changes in PtCO₂.