Independent and combined effects of inhaled nitric oxide, liquid perfluorochemical, and high-frequency oscillatory ventilation in premature lambs with respiratory distress syndrome

Acute lung injury caused by tidal volume ventilation in the premature lamb with respiratory distress syndrome (RDS) is characterized by progessive det erioration in gas exchange and lung inflammation. inhaled nitric oxide (iNO ) improves gas exchange and decreases lung neutrophil accumulation in prema ture lambs with RDS. Mechanical lung recruitment techniques such as high-fr equency oscillatory ventilation (HFOV) and partial liquid ventilation (PLV) also decrease lung injury and improve gas exchange in experimental models of neonatal respiratory failure. We hypothesized that two lung recruitment strategies (HFOV and PLV) would have similar effects on gas exchange and lu ng inflammatory, and would augment the response to iNO. We studied the indi vidual and combined effects of iNO, HFOV, and PLV (perflubron) in 31 extrem ely premature lambs (115 ed, 0.78 term) using seven mechanical ventilation protocols. Four groups were treated with conventional ventilation (control CV, CV + iNO, CV + PLV, and CV + PLV + iNO). Three groups were treated with HFOV (control HFOV, HFOV + iNO, HFOV + PLV). Control CV animals had progre ssive deterioration in gas exchange over the 4-h study period (a/AO(2) at 4 h = 0.06 +/- 0.01). In contrast, both HFOV and CV + PLV caused sustained i mprovements in oxygenation at 4 h (HFOV a/AO(2) = 0.27 +/- 0.06, CV + PLV a /AO(2) = 0.25 +/- 0.04; p < 0.01 versus CV). Both lung recruitment strategi es improved oxygenation when combined with iNO (5 ppm). Lung neutrophil acc umulation was reduced by HFOV, PLV, and iNO compared to CV. We conclude tha t HFOV and PLV with perflubron cause similar improvements in gas exchange a nd lung Inflammation in the premature lamb with severe RDS, and both strate gies augment the oxygenation response to iNO.