Nitric Oxide Pearls — Nitric Oxide, Inhaled, for Newborns with Persistent Pulmonary Hypertension — Clinical Pathway: ICU

Inhaled Nitric Oxide for Persistent Pulmonary Hypertension Clinical Pathway — N/IICU

Nitric Oxide Pearls

  • Nitric oxide (NO) effectively increases the intracellular cGMP in the smooth muscle cells of the pulmonary arteries, thereby decreasing the pulmonary vascular resistance.
  • For hypoxemic-term and near-term infants without congenital diaphragmatic hernias, inhaled nitric oxide (INO) reduces the incidence of combined outcome of death and need for ECMO. The reduction seems to be entirely a reduction in need for ECMO; mortality is not reduced.
  • Long-term follow-up studies (12–24 months) indicate that use of iNO does not alter either the incidence of chronic lung disease or neurodevelopmental impairment.
  • Early use of INO in the disease course does not reduce the use of ECMO, mortality, or improve other outcomes.
  • INO above 20 ppm have not been shown to provide more benefit.
  • About 25-30% of the severe PPHN does not respond to INO.
  1. Davidson, D. et al. (1999). Safety of withdrawing inhaled nitric oxide therapy in persistent pulmonary hypertension of the newborn. Pediatrics, 104, 231–236.
  2. Stenger, M.R. et al. (2012). Hospital variation in nitric oxide use for premature infants. Pediatrics, 129, e945-e951.
  3. Simsic, J.M. et al. (2014). Reducing variation in the use of inhaled nitric oxide. Pediatrics, 133, e1753-e1758.
  4. Clark, R.H. et al. (2000). Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn. N Engl J Med, 342, 469-474.
  5. Saleh A, Neiley E. Inhaled Nitric Oxide in Persistent Pulmonary Hypertension of the Newborn Refractory to High Frequency Ventilation. Critical Care 1999 3:7-10.
  6. Teng RJ., Wu TJ. Persistent pulmonary hypertension of the newborn. J Formos Med Asso. 2013 Apr. 112(4):177-184.
  7. Finer NN, Barrington KJ. Nitric oxide for respiratory failure in infants born at or near term. Cochrane Database Syst Rev. 2006;(4):CD000399.

iNO Mechanism of Action