Inhaled nitric oxide in preterm infants: an individual-patient data meta-analysis of randomized trials.

Journal article

BACKGROUND: Inhaled nitric oxide (iNO) is an effective therapy for pulmonary hypertension and hypoxic respiratory failure in term infants. Fourteen randomized controlled trials (n = 3430 infants) have been conducted on preterm infants at risk for chronic lung disease (CLD). The study results seem contradictory. DESIGN/METHODS: Individual-patient data meta-analysis included randomized controlled trials of preterm infants (<37 weeks' gestation). Outcomes were adjusted for trial differences and correlation between siblings. RESULTS: Data from 3298 infants in 12 trials (96%) were analyzed. There was no statistically significant effect of iNO on death or CLD (59% vs 61%: relative risk [RR]: 0.96 [95% confidence interval (CI): 0.92-1.01]; P = .11) or severe neurologic events on imaging (25% vs 23%: RR: 1.12 [95% CI: 0.98-1.28]; P = .09). There were no statistically significant differences in iNO effect according to any of the patient-level characteristics tested. In trials that used a starting iNO dose of >5 vs ≤ 5 ppm there was evidence of improved outcome (interaction P = .02); however, these differences were not observed at other levels of exposure to iNO. This result was driven primarily by 1 trial, which also differed according to overall dose, duration, timing, and indication for treatment; a significant reduction in death or CLD (RR: 0.85 [95% CI: 0.74-0.98]) was found. CONCLUSIONS: Routine use of iNO for treatment of respiratory failure in preterm infants cannot be recommended. The use of a higher starting dose might be associated with improved outcome, but because there were differences in the designs of these trials, it requires further examination.

Authors: Askie, L; Ballard, R; Cutter, G; Dani, C; Elbourne, D

• Journal: Pediatrics
• Volume: 128
• Issue: 4
• Pages: 729-739
• Publication date: 2011-10-01
• DOI: 10.1542/peds.2010-2725
• EISSN: 1098-4275
• ISSN: 0031-4005
• Language: English
• Keywords: Dose-Response Relationship, Drug; Respiratory Distress Syndrome, Newborn; Lung Injury; Infant, Premature; Treatment Outcome; Bronchodilator Agents; Infant, Newborn; Randomized Controlled Trials as Topic; Risk; Nitric Oxide; Drug Administration Schedule; Meta-analysis of Preterm Patients on Inhaled Nitric Oxide Collaboration; Administration, Inhalation; Humans