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Is nitric oxide effective in preterm infants?
  1. Nimish Subhedar,
  2. Chris Dewhurst
  1. Neonatal Unit, Liverpool Women’s NHS Foundation Trust
    Liverpool, UK
  1. Nimish Subhedar, Neonatal Unit, Liverpool Women’s NHS Foundation Trust, Liverpool L8 7SS, UK

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There is insufficient evidence to support the routine use of inhaled nitric oxide in preterms with respiratory failure

Inhaled nitric oxide is a selective pulmonary vasodilator used to treat neonates with respiratory failure. The first reports of its use were published in 1991 and the Food and Drug Administration (FDA) approved its use in the USA in 1999. However, it has only relatively recently received regulatory approval in Europe for use in hypoxaemic respiratory failure associated with pulmonary hypertension in neonates ⩾34 weeks’ gestation. Inhaled nitric oxide is often used outside the licensed indication (off-label) in preterm neonates.

Three randomised controlled trials investigating the efficacy of inhaled nitric oxide in preterm infants have been published recently.13 This article reviews the evidence base for the use of inhaled nitric oxide in the preterm population in the light of these new studies.


Inhaled nitric oxide is potentially beneficial in preterm infants for two main reasons. First, it may improve gas exchange in infants with established respiratory failure through enhanced ventilation–perfusion matching and/or a reversal of extrapulmonary shunting resulting in a lowering of respiratory support requirements and hence reduced ventilator and oxygen-induced lung injury.4 Second, inhaled nitric oxide has been shown to reduce lung inflammation and oxidant stress, preserve surfactant function, and promote lung growth and pulmonary vascular development in various laboratory studies and experimental models of bronchopulmonary dysplasia (BPD).510 These effects of inhaled nitric oxide may potentially attenuate preterm lung injury and therefore reduce the risk or severity of BPD if it is used at an early stage in the disease process.


Kinsella and colleagues randomised 793 preterm infants ⩽34 weeks’ gestation to receive 5 ppm inhaled nitric oxide or nitrogen placebo gas.1 Infants were eligible for inclusion into the study if they were …

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  • Competing interests: NS is a member of the Steering Committee of the European iNOCare Nitric Oxide Registry, which receives an unrestricted educational grant from INOTherapeutics.

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