NITRIC-OXIDE

Although persistent pulmonary hypertension of the newborn (PPHN) has been considered to be a relatively rare condition, there is increasing evidence that pulmonary vasoconstriction is a common finding in moderate and severe respiratory distress syndrome. High pressure, high rate ventilation may overcome this problem but it is associated with an unacceptably high incidence of pneumothorax and chronic lung disease. Vasodilators including tolazoline, prostacyclin and nitroprusside have a nonspecific effect, often producing systemic as well as pulmonary hypotension. Nitric oxide (NO) offers an exciting alternative therapy. NO is produced by the conversion of arginine to citrulline by NO synthase in the vascular endothelial cells. The NO then diffuses through to the underlying smooth muscle leading to relaxation. It then combines with haemoglobin to form small quantities of methaemoglobin, preventing spread of its effect elsewhere. The main potential toxic effect is due to the rapid conversion of NO to nitrogen dioxide in the presence of oxygen. Animal studies have shown that concentrations of NO up to 100 ppm are safe and also effective in relieving vasoconstriction induced by hypoxia, thromboxane analogues and infusions of group B haemolytic streptococcus. Preliminary studies on adults with respiratory distress syndrome have been encouraging showing reductions in pulmonary artery pressure and improvements in oxygenation without any changes in systemic blood pressure. Two small studies indicate that NO therapy is both effective and safe when given to full term babies with PPHN. Further data are urgently needed to find optimal concentrations so that multicentre studies can be carried out.