Inhaled Nitric Oxide in Early Neonatal Chronic Lung Disease: Three Hour Results 1627

Abstract

Background: Nitric oxide (NO) has been shown to be both a potent pulmonary vasodilator and bronchodilator. Several studies have demonstrated marked improvement in oxygenation of some infants with pulmonary hypertension treated with inhaled nitric oxide (INO). Because of its ability to increase flow in treated airways and pulmonary blood vessels, thereby allowing for possible improvement in ventilation-perfusion mismatching, INO may be useful for the treatment of early neonatal chronic lung disease. However, the possibility of unknown toxicity in this setting exists. We hypothesize that INO in a concentration of 20 ppm or less will result in improvement of pulmonary gas exchange in infants with early neonatal chronic lung disease. A Phase II, open-label study is being undertaken. All infants meeting enrollment criteria receive INO in addition to therapies already employed in their treatment. No therapy is stopped in order to provide INO to these patients. Infants are deemed eligible for the study based primarily on the following criteria: At least 7 days of age and evidence of developing chronic lung disease (based on radiographic changes, respiratory support requirements, and blood gas measurements). Exclusion criteria include the presence of significantly unstable pulmonary disease, initiation of corticosteroid orβ-agonist therapy in preceding 48 hr, recently diagnosed infection, thrombocytopenia. INO is administered at an initial dose of 20 ppm. Thus far 17 patients have been enrolled, with gestational age at birth of 25.1±1.2 wk, and birth weight 704±127g (mean±SD). Age at entry into study ranges from 10 to 109 days (median=21), with FiO2 at entry ranging from.42 to 1.0. Results show a range of responses in oxygen exchange, as judged both clinically and by calculation of oxygenation index (OI), with 14 of 19 trials (in 17 patients) showing a decrease in OI during the initial 2-3 hours of therapy (range of ΔOI: +2.3 to -15.7[+25 to -50%]; p=0.012). There has been no apparent toxicity, either clinically or by measurement of plasma methemoglobin. We conclude that INO may have a positive effect on early neonatal chronic lung disease.