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Abstract

Introduction: Mortality in pediatric patients with acute respiratory distress syndrome (ARDS) remains high despite improvements in care of these children. Inhaled nitric oxide (iNO) is a potent vasodilator that is delivered directly to areas of the ventilated lung to improve ventilation/perfusion mismatch resulting in improved oxygenation, and relieving pulmonary hypertension resulting from regional hypoxia. Recent studies have shown that the combined treatment of high frequency oscillatory ventilation and iNO improve oxygenation in children with ARDS. This implies the potential role of lung recruitment when used in conjunction with iNO to improve oxygenation. No study has examined the relationship of lung recruitment and effectiveness of iNO during conventional mechanical ventilation in pediatric patients. Methods: Young pigs (~10 kg) underwent lung injury with saline washout and ventilator-induced injury (20 ml/kg tidal volume, without peep). Lung injury was confirmed by PaO2/FiO2 ratio <200 and a decrease in the static compliance by 50% decrease from baseline. The piglets were then ventilated in a pressure control mode with the peak inspiratory pressures adjusted to achieve a tidal volume of 6 ml/kg. The FiO2 was kept at 1. A pulmonary artery (PA) catheter was placed for PA pressure monitoring and mixed venous saturation measurement. Inhaled NO was administered before and after lung recruitment at 5, 10 and 20 ppm concentrations. Lung recruitment was confirmed by measuring the static compliance and by the sum of PaO2+PaCO2 >= 400 mmHg. Arterial blood gas, mixed venous blood gas, lung compliance, hemodynamic parameters and methemoglobin levels were obtained at each iNO concentration after ventilating for 15 min. Each animal underwent section to evaluate gross pathology of lung injury and position of PA catheter. Results: The change in PaO2 level in recruited lungs was significantly higher than in non-recruited lungs at 5 and 20 ppm of iNO (5 ppm: delta PaO2 24 mmHg +/- 14 mmHg vs. 62 mmHg +/- 26 mmHg, p value 0.016; 20 ppm: delta PaO2 21 mmHg +/- 30 mmHg vs 67 mmHg +/- 29 mmHg, p value 0.039). There was no significance in the PaO2 response in non-recruited lungs vs. recruited lungs at an iNO concentration of 10 ppm. Methemoglobin levels, mixed venous saturations, and mean pulmonary artery pressures did not differ significantly at each iNO level in the recruited vs non-recruited lungs. Pearson correlation index for PaO2 in response to iNO and static compliance was ~0.18. Conclusions: Lung recruitment improves the response to iNO significantly at concentrations of 5 ppm and 20 ppm. During conventional mechanical ventilation, static compliance may be used as a predictor of iNO efficacy.