Inhaled Nitric Oxide in Premature Infants with the Respiratory Distress Syndrome

TLDR

Inhaled nitric oxide improves gas exchange, reduces pulmonary vascular lability, and decreases pulmonary inflammation. The study aimed to determine whether inhaled nitric oxide during the first week of life reduces chronic lung disease and death in premature infants with respiratory distress syndrome. In a randomized, double‑blind, placebo‑controlled trial, 207 infants <34 weeks gestation on mechanical ventilation received 10 ppm nitric oxide on day 1 followed by 5 ppm for six days, with ventilation mode randomized to intermittent mandatory or high‑frequency oscillatory ventilation. Inhaled nitric oxide lowered the combined incidence of chronic lung disease or death to 48.6 % versus 63.7 % in placebo (RR 0.76, 95 % CI 0.60–0.97, P = 0.03) and reduced severe intraventricular hemorrhage and periventricular leukomalacia to 12.4 % versus 23.5 % (RR 0.53, 95 % CI 0.28–0.98, P = 0.04).

Abstract

Inhaled nitric oxide improves gas exchange, decreases pulmonary vascular lability, and reduces pulmonary inflammation. We hypothesized that the use of inhaled nitric oxide would decrease the incidence of chronic lung disease and death in premature infants with the respiratory distress syndrome.We conducted a randomized, double-blind, placebo-controlled study of the effect of inhaled nitric oxide during the first week of life on the incidence of chronic lung disease and death in premature infants (less than 34 weeks' gestation) who were undergoing mechanical ventilation for the respiratory distress syndrome. Infants were randomly assigned to receive inhaled nitric oxide (10 ppm on day 1, followed by 5 ppm for six days) or inhaled oxygen placebo for seven days. We further randomly assigned the infants in each group to receive intermittent mandatory or high-frequency oscillatory ventilation.A total of 207 premature infants were enrolled. In the group given inhaled nitric oxide, 51 infants (48.6 percent) died or had chronic lung disease, as compared with 65 infants (63.7 percent) in the placebo group (relative risk, 0.76; 95 percent confidence interval, 0.60 to 0.97; P=0.03). There was no significant difference between the nitric oxide and placebo groups in the overall incidence of intraventricular hemorrhage and periventricular leukomalacia (33.3 percent and 38.2 percent, respectively), but the group given inhaled nitric oxide had a lower incidence of severe intraventricular hemorrhage and periventricular leukomalacia (12.4 percent vs. 23.5 percent; relative risk, 0.53; 95 percent confidence interval, 0.28 to 0.98; P=0.04). The type of ventilation had no significant effect on the outcome.The use of inhaled nitric oxide in premature infants with the respiratory distress syndrome decreases the incidence of chronic lung disease and death.