Association of bronchopulmonary dysplasia and hypercarbia in ventilated infants with birth weights of 500-1,499 g

Abstract

Bronchopulmonary dysplasia (BPD) continues to be a major pulmonary complication in very low birth weight (VLBW) and extremely low birth weight (ELBW) survivors of neonatal intensive care units (NICUs). Many factors including partial pressures of carbon dioxide (PaCO: (2)) have been implicated as possible causes. Permissive hypercapnia has become a more common practice in ventilated infants, but its effect on BPD is unclear. The hypothesis of this study was that hypercarbia is associated with increased BPD in infants with birth weights of 500-1,499 g. Nine hospitals were involved in this observational cohort study. Maternal and infant information including socio-demographics, antenatal steroids, gender, race, gestational age, birth weight, intubation and ventilator status, physiologic variables and data on therapies were collected by chart abstraction. SNAP scores were assigned. Candidate BPD risk factors, including cumulative exposures derived from blood gas and ventilation data in the first 6 days of life, were identified. Risk models were developed for 425 preterm infants who survived to 36 weeks post-menstrual age. BPD occurrence was associated with the cumulative burden of MAP >0 cm H(2)O in the first 6 days of life (P < 0.0001). After adjustment for the burden of MAP, the occurrence of hypercarbia (PaCO: (2) >50 torr) was associated with a greater incidence of BPD (P = 0.024). Among 293 intubated, mechanically ventilated infants, those with hypercarbia occurring only when MAP ≤ 8 cm H(2)O, a scenario more comparable to permissive hypercapnia, also had increased BPD incidence compared to infants without hypercarbia (P = 0.0003). Hypercarbia during the first 6 days of life was associated with increased incidence of BPD in these infants. Mechanically ventilated infants with hypercarbia during low MAP also had a significant increase in BPD. Permissive hypercapnia in ventilated infants needs further close review before the practice becomes even more widespread.

Fig. 1

Adjusted odds ratios and 95% confidence limits for predictors of BPD, based on 419 infants (six infants were excluded for missing Apgar score or MAP AUC). Results for the baseline factors and the AUCs for MAP >0 cm H₂O and Paco₂ >50 torr are based on the model in Table 5 without the nonsignificant linear term for the AUC for Paco₂>50 torr. Results for the remaining factors (AUC for Paco₂ <35 torr through Intralipid intake) were based on separately adding each factor to the logistic regression model described above. Odds ratios for continuous predictors correspond to the following unit changes: birth weight, 100 g; AUCs (linear terms), one standard deviation computed among those with AUC >0; others, one standard deviation

Fig. 2

Illustration of longitudinal area under the curve (AUC) computation for Paco₂ >50 torr by the trapezoidal rule. Data points for Paco₂ are connected by straight lines, and the area under the curve but above PaCO₂ = 50 torr is accumulated as the sum of the series of shaded trapezoidal and triangular areas. Thus the AUC for PaCO₂ >50 torr provides a measure of the cumulative burden of PaCO₂ exceeding 50 torr

Fig. 3

Model parameters for AUC variables. a The general case. b tHe case where β₁, the population slope, is zero