Introduction: Inhaled nitric oxide (INO) has been shown to reverse hypoxemia by two mechanisms-reversal of pulmonary hypertension and improvement in ventilation-perfusion matching. Infants with severe RDS have echocardiographic evidence of pulmonary hypertension as well as ventilation-perfusion mismatch. The purpose of this study was to determine if premature infants with severe RDS respond to INO.

Methods: Eleven infants with severe respiratory distress meeting study entry criteria were treated in random order with INO in four concentrations (1, 5, 10 and 20 ppm) and placebo. Arterial blood gas measurements were drawn prior to and at the end of each 15 minute period, and were used to determine PaO2/PAO2 ratio.

Results: Ten of 11 infants had a ≥25% increase in PaO2/PAO2 ratio. Five of 11 responded to INO with an increase in their PaO2/PAO2 ratio of ≥50%. The maximal response to INO occurred at 5 ppm in the majority of infants. Echocardiography prior to INO demonstrated a right-to-left shunt suggestive of pulmonary hypertension in 1 infant, a bidirectional shunt in 4 and a left-to-right shunt in 6. The one INO non-responder had a left to right shunt. All 11 infants had normal HUS prior to INO therapy, but 3 infants had ICH (Grade II-IV) identified immediately following the study and 4 additional infants were later found to have ICH (Grade II-IV). No infant had a significant increase in methemoglobin level.

Conclusions: This study indicates that premature infants with severe RDS have improved oxygenation in response to INO. The increase in oxygenation occurred at doses lower than used in most clinical trials. The role of INO in the infant with severe RDS deserves further investigation. The disturbing incidence of ICH in this small group of infants needs to be carefully considered prior to embarking upon larger trials. (Funded by NIH M01 RR00070)