Nitric oxide treatment and acute pulmonary inflammatory response in very premature infants with intractable respiratory failure shortly after birth.
OBJECTIVE
Premature infants with respiratory failure and early-onset pneumonia have low inducible nitric oxide synthase (NOS2) and no evidence of nitric oxide (NO) toxicity. However, inhalation of NO may not be indicated in sepsis because excessive NO generation has been reported. This prospective study was designed to test the hypothesis that inhaled NO is effective in a select group of small premature infants and that the responsiveness to NO is associated with low NOS2 enzyme.


METHODS
246 very low birthweight infants (birthweight <1500 g, VLBW) were screened for severe, intractable respiratory failure (oxygenation index >40, arterial-alveolar ratio for oxygen tension <0.10) that does not respond to two doses of surfactant within 5 h from birth. Infants with severe cardiac failure or a bleeding disorder were excluded. Five of the nine eligible cases received inhaled NO. They all had prolonged rupture of foetal membranes, early-onset pneumonia and persistent pulmonary hypertension.


RESULTS
All five responded strikingly, survived and appeared normal in follow-up. Airway specimens during the first day of life revealed very low NOS2, interleukin-1beta and surfactant protein A, compared with VLBW infants who had no acute infection despite histological chorioamnionitis. In early-onset pneumonia, NOS2 and other inflammatory mediators increased first during the recovery 1-2 d after birth.


CONCLUSIONS
VLBW infants with progressive respiratory failure and infection at birth have deficient pulmonary NOS2 and cytokine response. After surfactant therapy, these infants responded strikingly to inhaled NO. An acute pulmonary inflammatory response may contribute to respiratory adaptation in early-onset pneumonia.
Aikio
O
O
Department of Paediatrics, University of Oulu, Oulu, Finland.
Saarela
T
T
Pokela
M L
ML
Hallman
M
M
D000208:Acute Disease; D002097:C-Reactive Protein / Q000378:metabolism; D003131:Combined Modality Therapy; D005500:Follow-Up Studies; D006801:Humans; D006976:Hypertension, Pulmonary / Q000150:complications; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D019001:Nitric Oxide Synthase / Q000627:therapeutic use*; D011014:Pneumonia / Q000150:complications*; D012121:Respiration, Artificial / Q000379:methods; D012131:Respiratory Insufficiency / Q000188:drug therapy / Q000209:etiology* / Q000628:therapy*; D013997:Time Factors
D002097:C-Reactive Protein; D019001:Nitric Oxide Synthase