Inhaled Nitric Oxide Therapy in Premature Infants with
Mild to Moderate Respiratory Distress Syndrome
PIMOL SRISUPARP, M.D.*,
MARY HEITSCHMIDT, R.N., M.S.**,
MICHAEL D SCHREIBER, M.D.**
Affiliation : * Division of Neonatology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University,
Bangkok 10700, Thailand.
** Section of Neonatology, Department of Pediatrics, University of Chicago Children's Hospital, Pritzker School of
Medicine, Chicago, Illinois 60637, USA.
AbstractInhaled nitric oxide (iNO) therapy has been demonstrated to acutely improve oxygenation
in preterm infants with severe pulmonary disease. Administration of iNO to the premature infants
with less severe pulmonary illness has not yet been studied extensively. Therefore, the authors performed a pilot study enrolling thirty-four premature infants with respiratory distress syndrome (RDS)
within 72 hours of age, birth weight between 500-2,000 g, whose oxygenation indexes exceeded
our birthweight-specific criteria. Infants were randomly assigned to either treatment with (iNO
group; n = 16) or without (control group; n = 18) iNO. Inhaled NO was started at 20 ppm and
weaned to 5 ppm over 24-48 hours. Routine cranial ultrasonography was performed and the occurrence of intraventricular hemorrhage (IVH) was interpreted by an attending pediatric radiologist
unaware of the treatment group assignment. The study showed that the two groups were of similar
birth weight (mean±SEM) : control 901±73 g vs iNO 874±70 g; and gestational age : control 27.2±
0.5 wk vs iNO 26.8±0.5 wk. Other baseline parameters between the two groups were also similar.
The mean ages of the infants at the time of entry were 11.7±2.2 and 8.3±0.9 hours in the controls
and iNO group. The entry oxygenation index (01) did not differ between the two groups: control
11.9±2.2 vs iNO 10.8±1.50. After 30 minutes of iNO therapy, there was a 50 per cent increase in
partial pressure of oxygen tension (Pa02) and 15 per cent reduction in 01, (p =0.02 and p =0.04 vs
baseline, respectively). No statistical difference in the incidence of significant IVH (Grade III and IV)
was detected: control 27.8 per cent; iNO 25.0 per cent. The incidence of other acute complications
as well as early neonatal d~ath, were comparable between the groups. The mean methemoglobin concentration was 1.2±0.5 per cent. In conclusion, these preliminary data suggest that iNO, as used in
this protocol, acutely improves oxygenation without increasing significant IVH in premature infants
with mild to moderate RDS. These important findings serve to justify further study of the efficacy
of iNO on long term pulmonary outcome and mortality in this group of infants.
Keywords : Inhaled Nitric Oxide, Intraventricular Hemorrhage, Premature Infants, Safety
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