Inhaled Nitric Oxide for Respiratory Failure in Preterm Infants

Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database of Systematic Reviews 2017, Issue 1. Art. No.: CD000509. DOI: 10.1002/14651858.CD000509.pub5

Review question: Does giving inhaled nitric oxide gas to preterm infants with pulmonary disease improve survival without long-term brain or lung injury?

Background: Breathing failure in preterm newborn babies may be complicated by raised pressure within the vessels that carry blood to the lungs (pulmonary hypertension). Mechanically assisted ventilation is used to support such infants, and sedative medications may be given. Inhaled nitric oxide gas (iNO) helps regulate muscle tone in the arteries of the lungs and decreases pulmonary hypertension; therefore, it may reduce the need for assisted ventilation, leading to less lung injury. However, iNO has effects on platelet function and is believed to potentially increase bleeding (haemorrhage), in particular bleeding into the brain.

Study characteristics: Review authors found 17 randomised controlled trials of iNO in the preterm newborn through searches updated until January 2016. These trials studied preterm babies with very different baseline characteristics; therefore, we decided to divide them into three groups: (1) trials of babies treated in the first few days of life with severe lung disease, (2) studies providing treatment after the first few days of life to babies who were at increased risk of chronic lung disease and (3) trials providing routine early treatment for babies who experienced respiratory distress.

Key results: In none of the three groups of trials did iNO improve survival, and no consistent evidence suggests that iNO decreases lung injury. Studies in group 1 (early rescue treatment) reported a 20% increase in severe bleeding into the brain. This finding was close to statistically significant. The quality of the evidence was moderate to high.

This review of studies found that inhaled nitric oxide therapy does not appear to improve the chances of improved outcomes for preterm infants with pulmonary disease. When given to babies who were very ill, iNO did not seem to help and may have contributed to increased risk of intracranial haemorrhage.

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