Effect of Inhaled Nitric Oxide and High Frequency Oscillatory Ventilation in Meconium Aspiration Syndrome

Abstract

OBJECTIVE: To test the hypothesis that inhaled nitric oxide, when combined with high-frequency oscillatory ventilation, is an effective therapeutic agent in meconium aspiration syndrome. DESIGN: Prospective, interventional study. SETTING: The animal research laboratory at The Children's National Medical Center. SUBJECTS: Five newborn piglets, 1-2 wks old, weighing 3.6 +/- 0.2 kg. INTERVENTION: Animals were anesthetized, paralyzed, intubated, and ventilated. Catheters were placed in the femoral vein and artery and the pulmonary artery. After 1 hr of recovery, 10 mL/kg of 20% meconium in normal saline solution was insufflated into the lungs. Animals were ventilated with a SensorMedics oscillator to maintain arterial blood gases in a normal range (pH, 7.35-7.45; Paco2, 40-45 mm Hg [5.3-6.0 kPa]; Pao2, 70-90 mm Hg [9.3-12.0 kPa]). Ventilator settings were increased as needed until maximum settings as follows: Fio2, 1.00; proximal oscillatory pressure amplitude, 36 cm H2O; mean airway pressure, 25 cm H2O; frequency, 10 Hz. After a short period of stabilization, inhaled nitric oxide was administered. Concentrations of 40, 20, and 10 ppm were given and measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. To assure that there was no additive effect of inhaled nitric oxide, each dose was given for 20 mins followed by a 15-min normalization period at 0 ppm. MEASUREMENTS AND MAIN RESULTS: Physiologic measurements, ventilatory settings, arterial blood gases, and methemoglobin were recorded at each study period. Measurements were taken after each exposure to inhaled nitric oxide and after its discontinuation. Arterial saturation and partial pressure of arterial oxygen (Pao2) were significantly lower after meconium aspiration when compared with baseline. Administration of inhaled nitric oxide improved oxygenation without a significant decrease in pulmonary artery pressure. CONCLUSION: In this model of meconium aspiration syndrome, short-term exposure to inhaled nitric oxide when combined with high-frequency oscillatory ventilation improved oxygenation secondary to better distribution of inhaled nitric oxide. The increase in oxygenation may be secondary to improved ventilation perfusion mismatch, as the primary etiology of hypoxia in this model may be a combination of parenchymal lung disease and pulmonary hypertension.