Randomized Trial of Permissive Hypercapnia in Preterm Infants: A Pilot Study. • 962

Retrospective studies suggest that ventilatory strategies that tolerate mild hypercapnia and/or prevent hypocapnia during the first days of life may reduce chronic lung disease (CLD). We performed a randomized trial to compare the effects of permissive hypercapnia (H, PaCO₂45-55 torr) versus normocapnia (N, PaCO₂35-45 torr) during the first 96 hours of life in neonates weighing 601 to 1250 gm who received mechanical ventilation (MV) and surfactant. The primary outcome measure was total days on MV. Extubation criteria were pH ≥ 7.25, ventilator rate ≤ 10/min, and peak inspiratory pressure (PIP) ≤ 19 cm H₂O. All patients received aminophylline prior to extubation. Ventilator-dependent infants at 10 days received 7 days of dexamethasone. Reintubation was performed for a pH < 7.20. Patients(n=49) were randomized at a mean age of 10 hours of life (H=24, N=25). The groups were comparable for gestational age (26 ± 1 weeks), birth weight(H 852 ± 156 gm, N 856 ± 173 gm), gender, race, prenatal steroid use, and blood gas values, oxygenation index, and ventilator settings prior to randomization. The total number of days on MV (median, 25-75 quartiles) was 2.5, 1.5-11.2 in the H group and 9.2, 1.5-22.5 in the N group (p=0.17, Mann-Whitney). The number of patients on MV throughout the 96 hours after randomization was lower in the H group (figure). During that time, the ventilated patients in the H group had a higher PaCO₂ and lower PIP, mean airway pressure, and ventilator rate than those in the N group (repeated measures ANOVA, all p<0.05). The percentage of patients requiring reintubation (H 66% vs N 54%), supplemental O₂ at 28 days of life (H 43% vs N 63%), and the total days on O₂(median, 25-75 quartiles: H 15, 4-50 vs N 32, 17-47) did not differ between the groups. There were no differences in mortality, air leaks, patent ductus arteriosus, intraventricular hemorrhage, periventricular leukomalacia, or retinopathy of prematurity. A ventilatory strategy of permissive hypercapnia in preterm infants may reduce the number of days on MV without increasing adverse outcomes.