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Independent and Combined Effects of Inhaled Nitric Oxide, Liquid Perfluorochemical, and High-Frequency Oscillatory Ventilation in Premature Lambs With Respiratory Distress Syndrome* FREE TO VIEW

John P. Kinsella, MD; Thomas A. Parker, MD; Henry Galan, MD; Brett C. Sheridan, MD; Steven H. Abman, MD
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*From the Pediatric Heart Lung Center, and the Departments of Pediatrics (Drs. Kinsella, Parker, and Abman), Obstetrics and Gynecology (Dr. Galan), and Surgery (Dr. Sheridan), University of Colorado School of Medicine, Denver, CO.

Correspondence to: John P. Kinsella, MD, Pediatric Heart Lung Center, Department of Pediatrics, Children’s Hospital, 1056 East 19th Ave, Denver, CO 80218

Chest. 1999;116(suppl_1):15S-16S. doi:10.1378/chest.116.suppl_1.15S
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Acute lung injury during conventional ventilation in the premature lamb with respiratory distress syndrome (RDS) is characterized by progressive deterioration in gas exchange and lung inflammation. Inhaled nitric oxide (iNO), high-frequency oscillatory ventilation (HFOV), and partial liquid ventilation (PLV) have been proposed as new therapies that may improve oxygenation while minimizing the severity of acute lung injury. The relative and combined effectiveness of these three therapies in improving gas exchange and decreasing inflammation in severe RDS is uncertain. We hypothesized that the two lung recruitment strategies (HFOV and PLV) would have similar effects on gas exchange and lung inflammation, and would augment the response to low-dose iNO. To test this hypothesis, we studied the individual and combined effects of iNO, HFOV, and PLV in 31 extremely premature lambs (115 days, 0.78 term; 147 days = term) using seven mechanical ventilation protocols.

Premature animals were delivered by cesarean section and treated with surfactant before beginning mechanical ventilation for 4 h with fraction of inspired oxygen = 1.00. Four groups were treated with conventional ventilation (CV control, n = 5; CV + iNO, n = 5; CV + PLV, n = 5; CV + PLV + iNO, n = 4). Three groups were treated with HFOV (HFOV control, n = 5; HFOV + iNO, n = 4; HFOV + PLV, n = 3). Arterial blood gases were recorded hourly. At the end of the study, the lungs were prepared for histology and assessments of lung neutrophil accumulation using a myeloperoxidase assay. We found that control CV animals had progressive deterioration in gas exchange over the 4-h study period (arterial-alveolar oxygen ratio [a/AO2] at 4 h = 0.07 ± 0.01). In contrast, both HFOV and CV + PLV improved oxygenation at 4 h (HFOV a/AO2 = 0.27 ± 0.06; PLV a/AO2 = 0.25 ± 0.04; p < 0.01 vs CV). Both lung recruitment strategies improved oxygenation when combined with iNO (5 ppm). PLV did not improve oxygenation when combined with HFOV, but allowed the use of lower airway pressures. Lung neutrophil accumulation (myeloperoxidase assay, units per gram of lung tissue) was markedly reduced by HFOV (0.06 ± 0.06), CV + PLV (0.16 ± 0.08), and CV + iNO (0.11 ± 0.04) compared with CV (0.53 ± 0.20, p < 0.05).

We conclude that HFOV and PLV cause similar improvements in gas exchange and equivalent attenuation of lung neutrophil accumulation in extremely premature lambs with RDS. Both lung recruitment strategies augmented the oxygenation response to low-dose iNO. We speculate that these lung recruitment strategies could favorably modulate the inflammatory component of lung injury in clinical RDS, and that combined treatments may improve the respiratory outcome of premature neonates.




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