Dose‐response to inhaled nitric oxide in acute hypoxemic respiratory failure of newborn infants: A preliminary report

In acute hypoxemic respiratory failure of term and near‐term neonates, extra‐ and intrapulmonary right‐to‐left shunting contribute to refractory hypoxemia. Inhaled nitric oxide (NO) decreases pulmonary arterial pressure and improves ventilation–hperfusion mismatch in a variety of animal models and selected human patients. We report on 10 consecutive term and near–term newborns with severe acute hypoxemic respiratory failure due to diaphragmatic hernia, meconium aspiration syndrome, group B streptococcus sepsis, pneumonia or acute respiratory distress syndrome, who received increasing doses of inhaled NO (up to 80 ppm) to improve the arterial partial pressure of oxygen (PaO 2 ). The response to NO and the optimum NO concentration which improved PaO 2 varied considerably between patients. Improvement of PaO 2 was absent or poor (less than 10 mm Hg) in the 4 newborns with meconium aspiration syndrome and in 1 patient with congenital diaphragmatic hernia, while in the other 5 patients inhaled NO increased the mean (± SE) PaO 2 from 41 ± 6 to 57 ± 9 mm Hg ( P < 0.05). Optimum NO concentrations determined by dose‐response measurements performed during the first 8 hr of NO inhalation were 8–16 ppm except for 2 newborns with congenital diaphragmatic hernia who required 32 ppm to effectively increase PaO 2 . Four of the 5 patients in whom the PaO 2 rose by more than 10 mm Hg received inhaled NO for extended periods of time (5 to 23 days) with no signs of tachyphylaxis. The optimum NO concentration dropped to less than 3 ppm after prolonged mechanical ventilation or when intravenous prostacyclin was given concomitantly. The response to inhaled NO and the optimum NO concentration to improve arterial oxygenation were virtually identical with conventional and high frequency oscillatory ventilation (HFO). We conclude that the optimal concentration of NO to improve PaO 2 of neonates with acute hypoxemic respiratory failure varies considerably between patients, shows temporal variations, and requires individual and repeated adjustments of the concentration of inhaled NO.