Inhaled nitric oxide therapy improves oxygenation and reduces the need for ECMO in neonates with hypoxic respiratory failure. Little information is available regarding patient responses to INO DR. We investigated relationships associated with the change in PaO2 during INO DR in neonates with hypoxic respiratory failure at medical centers participating in the Neonatal Inhaled Nitric Oxide Study (NINOS). PaO2s surrounding 505 INO DR attempts with constant FiO2 and ventilator settings were reviewed. Changes in PaO2 associated with INO DR were calculated. In a successful DR the PaO2 remained> 50 torr with ≤ 25% decline from pre-wean values, (≤ 50% decline if FiO2 < 0.50 or INO > 20 ppm). The relationships between the change in PaO2 associated with INO DR and pre-wean PaO2, acuity of illness, mode of ventilation (IMV vs. HFOV), treatment with surfactant and history of pulmonary hypertension were examined. Overall, 78% of INO DRs were successful with a mean decline in PaO2 of 18.7 ± 40.2 torr (p<0.0001). The largest declines and the majority of unsuccessful DRs occurred with attempts to wean off INO; only 35% of DRs from 5 to 0 ppm were successful (mean decline in PaO2 of 47.1 ± 44.9 torr) and 72% of DRs from 1 to 0 ppm were successful(mean decline in PaO2 of 30.3 ± 41.1 torr). Although the success of INO DR was independent of the pre-wean PaO2, the decline in PaO2 with DR was inversely related to the pre-wean PaO2; being 1.2 ± 22.3 torr for PaO2≤ 80, 14.4 ± 24.3 torr for PaO2 > 80 ≤ 120, 20.3 ± 40.2 torr for PaO2 > 120 ≤ 160 and 39.4 ± 57.7 torr for PaO2 > 160. INO DR in patients with lower severity of illness experienced greater declines in PaO2. INO DR in surfactant treated patients resulted in significantly smaller declines in PaO2 (-15.9 ± 37.8 vs. -28.8 ± 46.5 torr, p= 0.0026). Although mode of ventilation was not associated with a significant change in PaO2 during INO DR, patients treated with HFOV tended to experience greater declines vs. IMV (-21.6 ± 37.0 vs. -15.5 ± 43.4 torr, p= 0.0938). The primary diagnosis and history of echocardiographic pulmonary hypertension were not associated with significant changes in PaO2 during INO DR. We conclude that while the majority of INO DRs are successful, the majority of failures occur when attempting to discontinue INO therapy; PaO2s≤ 80 are not a contraindication for INO DR and the treatment with surfactant is associated with a reduced decline in PaO2 during INO DR.
