Partial Pressure of Carbon Dioxide in Extremely Low Birth Weight Infants Supported by Nasal Prongs Continuous Positive Airway Pressure

METHODS

RESULTS

Seventy-six neonates who weighed <1000 g were sequentially born at our institution and admitted to the NICU during the study period. Five infants died, and 2 were transferred to the Children’s Hospital for surgical reasons during the first week of life. Of the surviving 69 infants, 62 medical records were available for review.

Twenty-four infants were never intubated and were treated with NCPAP alone (group 1). Nineteen infants were initially intubated and ventilated but weaned to NCPAP in <48 hours of life (group 2). Another 19 infants were treated mainly with mechanical ventilation during the first week of life (group 3). The demographic and perinatal data of this study population are included in Table 1.

There was no significant difference between the daily average Pco₂ levels of group 1 and group 2 during the first week of life (Table 2). For both groups, average Pco₂ levels were highest on the first day of life (group 1: 41.56 ± 5.88 mm Hg; group 2: 43.25 ± 10.76 mm Hg) and lowest on the second day of life (group 1: 37.55 ± 6.53 mm Hg; group 2: 37.79 ± 6.61 mm Hg). Overall mean Pco₂ level during the first week of life for infants who were breathing spontaneously on NCPAP was 39.73 ± 1.78 mm Hg. The trend of daily Pco₂ averages for both groups is shown in Fig 1. Average daily pH values for the infants in group 1 ranged from 7.30 to 7.35 (Table 3).

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Fig 1.

Average daily Pco₂ during the first week of life are shown as a function of days of life (DOL) in infants who were treated with NCPAP (group 1) and mechanically ventilated and weaned to NCPAP within the first 48 hours of life (group 2). The Pco₂ averages near 40 mm Hg and are similar for both groups.

There was no difference between the daily average minimum Pco₂ levels among the 3 groups (Fig 2). The infants who were treated mainly with mechanical ventilation, however, had significantly higher maximum Pco₂ levels compared with the other 2 groups during days 2 through 7 of life (P < .05). This difference was not found on the first day of life (P = .27). Group 3 had daily average maximum Pco₂ levels ranging between 54.51 and 57.52 mm Hg (Fig 3).

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Fig 2.

Average daily minimum Pco₂ for groups 1 and 2 and in infants who were mechanically ventilated for >48 hours (group 3), as a function of DOL. There is no significant difference among the 3 groups.

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Fig 3.

Average daily maximum Pco₂ levels for all 3 groups are shown as a function of age in days (DOL). The maximum Pco₂ in group 3 is significantly higher than in groups 1 and 2 on days 2 through 7 of life.

None of the infants in group 1 or 2 had grade 3 or higher intraventricular hemorrhage (IVH) or stage 3 or higher retinopathy of prematurity. In group 3, 3 infants developed IVH grade 3 or 4 (P = .05) and 2 infants developed retinopathy of prematurity stage 3 (P = .18). There was a trend for a decreased incidence of BPD in group 1 (16.7%) compared with group 2 (36.8%) and group 3 (42.1%) that did not reach significance (P = .14). A total of 5 infants died; 3 from group 1 (necrotizing enterocolitis, sepsis and airway obstruction) and 2 from group 3 (pulmonary hemorrhage and hyaline membrane disease).

DISCUSSION

ELBW infants who were supported with early NCPAP could maintain Pco₂ levels that averaged approximately 40 mm Hg. ELBW infants who were treated solely with NCPAP did not show any significant difference in their Pco₂ levels when compared with those who were initially ventilated and then weaned to NCPAP at a later time.

Pco₂ of blood is determined by carbon dioxide production and alveolar ventilation, and the latter is affected by minute ventilation, dead space volume, and blood flow. The normal reference range for Pco₂ levels in children has been generally accepted to be between 33 and 45 mm Hg.¹¹ Healthy term infants between 2 weeks and 9 months of life have been reported to have Pco₂ levels of 40.5 ± 3 kPa (5.4 ± 0.4 kPa).¹² This information has been adapted to the treatment of the ELBW infant; however, no data are available to determine whether these respiratory mechanics are applicable to this population.

In a previous report by Lindner et al,³ initial Pco₂ in ELBW infants who were supported with NCPAP was higher when compared with those who were intubated and mechanically ventilated in the delivery room (54 ± 13 vs 42 ± 17 mm Hg, respectively). These levels did decrease within the first day of life to 48 mm Hg (range: 32–57 mm Hg) and were maintained during the first week at 47 mm Hg (range: 39–49 mm Hg). Their management practice was different from ours. ELBW infants in their study were initially given distending pressure of 20 cm of water via a mechanical ventilator through a nasal pharyngeal tube before CPAP initiation. In addition, we use a water-seal CPAP device in place of ventilator-delivered CPAP. Finally, we have a strict policy with airway care requiring appropriate positioning and airway suctioning every 2 to 3 hours.

Extreme levels of Pco₂ in the ELBW infant can have adverse effects on neonates. Hypocapnia has been reported to increase the risk for CLD^7,8,13,14 and has been associated with poor neurologic outcomes, including periventricular leukomalacia,^8,15–17 cerebral palsy, and neurodevelopmental delay.^8,15 Severe hypercapnia, however, has likewise been linked to adverse outcomes such as IVH.^8,18,19

We found that ELBW infants who were maintained on NCPAP did not develop carbon dioxide (CO₂) retention, with results similar to those seen with intermittent mechanical ventilation (group 3). Many of these infants, when allowed to breathe independently, settled at a Pco₂ level in the low 30s during the first few days of life. This low Pco₂ level does not seem to be a compensatory response to significant metabolic acidosis. This may be of relevance because CPAP has been associated with a decreased incidence of IVH.^2,3 IVH in the premature infant is attributed to the lack of cerebral autoregulation.¹⁸ We speculate that low Pco₂ levels in this subgroup may serve as a protective measure to compensate for this lack of autoregulation. Of note, none of the infants in groups 1 and 2 had any grade 3 or 4 IVH or periventricular leukomalacia.

Our finding that prolonged mechanical ventilation during the first week after birth is associated with higher daily maximum Pco₂ levels can be attributed to increased severity of respiratory distress syndrome (RDS) and could be an early harbinger of ongoing lung disease. This more severe RDS in the mechanical ventilation group may be reflected in the lower Apgar scores of this group. Another important perinatal factor is maternal glucocorticoid use, for which data were not available for this study. However, in other aspects that may suggest a more severe degree of illness in the ventilation group (gestational age, birth weight, percentage of boys), we did not find significant differences from the other 2 groups. In fact, all 3 groups had similar numbers of ELBW infants with birth weight between 500 and 750 g (10 of 24 for group 1, 9 of 19 for group 2, and 10 of 19 for group 3). Even so, it came as no surprise that patients who require prolonged mechanical ventilation have some form of intrinsic lung disease with hypercapnia. It is not the aim of this study to compare Pco₂ levels of these infants with those on NCPAP. Rather, these data show that ELBW infants with moderate RDS can be supported adequately with NCPAP and not show evidence of respiratory insufficiency or Pco₂ retention.

The clinical practice to allow Pco₂ to rise to ameliorate the incidence of CLD in the premature infant has been revisited recently.^20,21 There is no consensus on acceptable Pco₂ levels. Instead, one may look at Pco₂ levels in neonates who are breathing spontaneously without distress. The parameters seen in these spontaneously breathing infants can help us to arrive at optimal settings for infants who require mechanical ventilation.

The results of this study show that a short period of mechanical ventilation does not affect the Pco₂ level in the ELBW infant after extubation. However, this comparison was limited only to the first week of life, and no additional information can be determined regarding other effects of this intervention. Surprising, ELBW infants who are intubated for brief period (<24 hours) experience a significantly higher incidence of CLD compared with ELBW infants on NCPAP.²² Although infants who are treated for the most part with mechanical ventilation during the first week of life seem to have a higher daily maximum Pco₂, any clinical impairment associated with such hypercapnia remain unknown.

CONCLUSIONS

During the first week of life, the spontaneously breathing ELBW infant has an average daily Pco₂ near 40 mm Hg. Those levels of Pco₂ seem to be unaffected by any brief time on mechanical ventilation. Infants who are mechanically ventilated for more extensive periods of time (>48 hours) have an elevated maximum Pco₂ during the first week of life. Additional studies are required to detect possible adverse neurodevelopmental and pulmonary changes associated with increased levels of Pco₂.