Multicenter randomized controlled trial of the effects of inhaled nitric oxide therapy on gas exchange in children with acute hypoxemic respiratory failure

Objectives and background: To determine whether inhaled nitric oxide (iNO) therapy can attenuate the progression of lung disease in acute hypoxemic respiratory failure, we performed a multicenter, randomized, masked, controlled study of the effects of prolonged iNO therapy on oxygenation. We hypothesized that iNO therapy would improve oxygenation in an acute manner, slow the rate of decline in gas exchange, and decrease the number of patients who meet pre-established oxygenation failure criteria. Study design: A total of 108 children (median age 2.5 years) with severe acute hypoxemic respiratory failure from 7 centers were enrolled. After consent was obtained, patients were randomized to treatment with iNO (10 ppm) or mechanical ventilation alone for at least 72 hours. Patients with an oxygenation index greater than or equal to 40 for 3 hours or greater than or equal to 25 for 6 hours were considered treatment failures and exited the study. Results: Patient age, primary diagnosis, pediatric risk of mortality score, mode of ventilation, and median oxygenation index (35 +/- 22 vs 30 +/- 15; iNO vs control; mean +/- SEM) were not different between groups at study entry. Comparisons of oxygenation indexes during the first 12 hours demonstrated an acute improvement in oxygenation in the;NO group at 4 hours (-10.2 vs -2.7 mean values; P < .014) and at 12 hours (-9.2 vs -2.8; P < .007). At 12 hours 36% of the control group met failure criteria in contrast with 16% in the iNO group (P < .05). During prolonged therapy the failure rate was reduced in the iNO group in patients whose entry oxygenation index was greater than or equal to 25 (P < .04) and in immunocompromised patients (P < .03). Conclusions: We conclude that iNO causes an acute improvement in oxygenation in children with severe AHRF Two subgroups (immunocompromised and an entry oxygen index greater than or equal to 25) appear to have a more sustained improvement in oxygenation, and we speculate that these subgroups may benefit from prolonged therapy.