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Pediatr Pulmonol. 2017 Nov;52(11):1461-1468. doi: 10.1002/ppul.23843.

Nitric oxide for the treatment of preterm infants with severe RDS and pulmonary hypertension.

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Division of Neonatology, Careggi University Hospital of Florence, Florence, Italy.
Department of Neurosciences, Psychology, Drug Research, and Child Health, University of Florence, Florence, Italy.



Inhaled nitric oxide (iNO) cannot be recommended for the routine treatment of respiratory failure in premature neonates, but it has been suggested that the effectiveness of iNO therapy should be further studied in more select preterm infants, such as those with persistent pulmonary hypertension of the newborn (PPHN).


To evaluate the frequency of PPHN in very preterm infants with severe respiratory distress syndrome (RDS), to assess the effectiveness of iNO in these patients, and to individuate possible predictive factors for the response to iNO in preterm infants with RDS.


We retrospectively studied infants <30 weeks of gestational age or birth weight <1250 g, who were affected by severe RDS and treated with iNO during the first week of life. Clinical characteristics of infants with or without echocardiographic diagnosis of PPHN were compared, as well as those of responder or no responder to iNO therapy. Effectiveness of iNO was evaluated by recording changes of MAP, FiO2 , SpO2 /FiO2 ratio, and oxygenation index (OI) before, and 3 ± 1, 6 ± 1, 12 ± 3, 24 ± 6, 48 ± 6, and 72 ± 12 h after beginning therapy.


We studied 42 (4.6%) infants, of whom 28 (67%) had PPHN and 14 (33%) did not. iNO therapy was associated with improved oxygenation in both the groups but it was quicker in the PPHN than in the no PPHN group. Multivariate analysis showed that FiO2 >0.65, diagnosis of PPHN, and birth weight >750 g independently predicts effectiveness of iNO in very preterm infants with RDS.


We found that PPHN is a frequent complication of severe RDS in very preterm infants and iNO therapy can improve their oxygenation earlier than in infants without PPHN. iNO therapy is not recommended for the routinely treatment of RDS in premature neonates but in cases of concurrent diagnosis of PPHN it should be considered carefully.


nitric oxide; preterm infant; pulmonary hypertension; respiratory distress syndrome

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