A dose response study of inhaled nitric oxide in hypoxic respiratory failure in preterm infants

Abstract Background Inhaled nitric oxide (iNO) is used widely in newborn infants with hypoxic respiratory failure, despite the known and theoretical toxicity of iNO, and a relative lack of information about appropriate doses. Aim To determine whether a dose–response relationship existed for iNO in preterm infants. Design A four-period, four-dose, cross-over design was used with iNO given for 15 min in a randomised sequence in concentrations of 5, 10, 20 and 40 parts per million (ppm), with a minimum 5 min wash-out period. Data on ventilatory, blood gas and other physiological measurements were recorded before and at the end of each period. The relationship of clinical response with iNO dose and period was analysed using multivariate regression. Subjects Infants with gestational age Outcome measure A clinically significant dose–response was defined as a rise in the post-ductal arterial oxygen tension (PaO 2 ) of at least 3 kPa. Results Thirteen infants were recruited. At trial entry, ten were p  = 0.34). Conclusion No evidence of a dose–response relationship with iNO was found in this study of very preterm infants with respiratory failure.