MULTICENTER CONTROLLED CLINICAL-TRIAL OF HIGH-FREQUENCY JET VENTILATION IN PRETERM INFANTS WITH UNCOMPLICATED RESPIRATORY-DISTRESS SYNDROME

Objective. To test the hypothesis that high-frequency jet ventilation (HFJV) will reduce the incidence and/or severity of bronchopulmonary d ysplasia (BPD) and acute airleak in premature infants who, despite sur factant administration, require mechanical ventilation for respiratory distress syndrome. Design. Multicenter, randomized, controlled clinic al trial of HFJV and conventional ventilation (CV). Patients were to r emain on assigned therapy for 14 days or until extubation, whichever c ame first. Crossover from CV to HFJV was allowed if bilateral pulmonar y interstitial emphysema or bronchopleural fistula developed. Patients could cross over to the other ventilatory mode if failure criteria we re met. The optimal lung volume strategy was mandated for HFJV by prot ocol to provide alveolar recruitment and optimize lung volume and vent ilation/perfusion perfusion matching, while minimizing pressure amplit ude and O-2 requirements. CV management was not controlled by protocol . Setting. Eight tertiary neonatal intensive care units. Patients. Pre term infants with birth weights between 700 and 1500 g and gestational age <36 weeks who required mechanical ventilation with FIO2 >0.30 at 2 to 12 hours after surfactant administration, received surfactant by 8 hours of age, were <20 hours old, and had been ventilated for <12 ho urs. Outcome Measures. Primary outcome variables were BPD at 28 days a nd 36 weeks of postconceptional age. Secondary outcome variables were, survival, gas exchange, airway pressures, airleak, intraventricular h emorrhage (IVH), periventricular leukomalacia (FVL), and other nonpulm onary complications. Results. A total of 130 patients were included in the final analysis; 65 were randomized to HFJV and 65 to CV. The grou ps were of comparable birth weight, gestational age, severity of illne ss, postnatal age, and other demographics. The incidence of BPD at 36 weeks of postconceptional age was significantly lower in babies random ized to HFJV compared with CV (20.0% vs 40.4%). The need for home oxyg en was also significantly lower in infants receiving HFJV compared wit h CV (5.5% vs 23.1%). Survival, incidence of BPD at 28 days, retinopat hy of prematurity, airleak, pulmonary hemorrhage, grade I-II IVH, and other complications were similar. In retrospect, it was noted that the traditional HFJV strategy emphasizing low airway pressures (HF-LO) ra ther than the prescribed optimal volume strategy (HF-OPT) was used in 29/65 HFJV infants. This presented a unique opportunity to examine the effects of different HFJV strategies on gas exchange, airway pressure s, and outcomes. HF-OPT was defined as increase in positive end-expira tory pressure (PEEP) by greater than or equal to 1 cm H2O from pre-HFJ V baseline and/or use of PEEP of greater than or equal to 7 cm H2O. Se vere neuroimaging abnormalities (PVL and/or grade III-IV IVH) were not different between the CV and HFJV infants. However, there was a signi ficantly lower incidence of severe IVH/PVL in HFJV infants treated wit h HF-OPT compared with CV and HF-LO. Oxygenation was similar between C V and HFJV groups as a whole, but HF-OPT infants had better oxygenatio n compared with the other two groups. There were no differences in Pac o(2) between CV and HFJV, but the Paco(2) was lower for HF-LO compared with the other two groups. The peak inspiratory pressure and Delta P (peak inspiratory pressure-PEEP) were lower for HFJV infants compared with CV infants. Conclusions. HFJV reduces the incidence of BPD at 36 weeks and the need for home oxygen in premature infants with uncomplic ated RDS, but does not reduce the risk of acute airleak. There is no i ncrease in adverse outcomes compared with CV. HF-OPT improves oxygenat ion, decreases exposure to hypocarbia, and reduces the risk of grade I II-IV IVH and/or PVL.