Effects of hypocarbia on the development of cystic periventricular leukomalacia in premature infants treated with high-frequency jet ventilation.

BACKGROUND AND OBJECTIVE: Previous data from our institution indicate that mechanically ventilated premature infants are at increased risk for cystic periventricular leukomalacia (CPVL), particularly if hypocapnia occurs. High-frequency jet ventilation (HFJV) may produce substantial hypocapnia. We sought to investigate whether hypocapnia during HFJV is associated with the development of CPVL.

METHODS: Sixty-seven premature infants (mean gestational age, 27.2 weeks; mean birth weight, 1001 g) underwent HFJV for a mean of 44 (range, 8 to 70) hours during the first 3 days of life. All infants were followed with serial neurosonograms at least weekly until 6 to 8 weeks of age and every 2 to 4 weeks thereafter until discharge. To assess the cumulative effects of hypotension, acidosis, hypoxemia, and hypocarbia during the first 3 days of life on the development of PVL, we developed a quantitative assessment in which we assigned threshold levels at particular critical values of these parameters (such as a mean PaCO2 of 20 mm Hg) and calculated an area above the curve between longitudinally connected values of these parameters and the threshold levels.

RESULTS: Nine of the 67 infants died before 21 days of life. Of the 58 who survived beyond 21 days, large CPVL (> 5 mm in size) developed in 18 infants. Infants with cysts were similar in birth weight, gestational age, and virtually all other antepartum, intrapartum, and postpartum parameters compared with the 40 neonates in whom CPVL did not develop. However, infants with CPVL were significantly more likely to have moderate or severe periventricular echodensities preceding development of CPVL and periventricular echodensities that persisted for a longer period. We did not find an effect of hypotension, acidosis, or hypoxemia on the development of CPVL. There were no differences in the mean PaCO2, the absolute low PaCO2 values, the ranges of low PaCO2 between groups, or area above the curve measurements at threshold levels of 15 and 20 mm Hg, respectively. However, logistic regression analysis revealed that infants with CPVL were independently significantly more likely to have greater cumulative hypocarbia below a threshold level of 25 mm Hg during the first day of life (odds ratio, 5.43; 95% confidence interval, 1.33 to 22.2).

CONCLUSIONS: Hypocarbia produced by treatment with HFJV during the first 3 days of life is associated with the subsequent development of CPVL. The mechanisms for the development of CPVL among premature infants treated with HFJV need to be established.