Elsevier

The Journal of Pediatrics

Volume 166, Issue 2, February 2015, Pages 365-369.e1
The Journal of Pediatrics

Original Article
Multicenter Randomized Controlled Trial of Inhaled Nitric Oxide for Pediatric Acute Respiratory Distress Syndrome

https://doi.org/10.1016/j.jpeds.2014.10.011Get rights and content

Objectives

To test the hypothesis that inhaled nitric oxide (iNO) would lead to improved oxygenation and a decrease in duration of mechanical ventilation in pediatric patients with acute respiratory distress syndrome.

Study design

A total of 55 children with acute respiratory distress syndrome were enrolled from 9 centers. Patients were randomized to iNO or placebo and remained on the study drug until death, they were free of ventilator support, or day 28 after the initiation of therapy.

Results

Mean baseline oxygenation indexes (OIs) were 22.0 ± 18.4 and 25.6 ± 14.9 (iNO and placebo groups, respectively, P = .27). There was a trend toward an improved OI in the iNO group compared with the placebo group at 4 hours that became significant at 12 hours. There was no difference in the OI between groups at 24 hours. Days alive and ventilator free at 28 days was greater in the iNO group, 14.2 ± 8.1 and 9.1 ± 9.5 days (iNO and placebo groups, respectively, P = .05). Although overall survival at 28 days failed to reach statistical significance, 92% (22 of 24) in the iNO group and 72% (21 of 29) in the placebo group (P = .07), the rate of extracorporeal membrane oxygenation−free survival was significantly greater in those randomized to iNO 92% (22 of 24) vs 52% (15 of 29) for those receiving placebo (P < .01).

Conclusion

The use of iNO was associated with a significantly reduced duration of mechanical ventilation and significantly greater rate of extracorporeal membrane oxygenation–free survival.

Section snippets

Methods

The study protocol was approved by the institutional review board at each participating center. Patient enrollment took place from 2003 through 2005. Because of slow enrollment, the study was terminated prematurely, and because of the acquisition of INO Therapeutics by Ikaria and a shift in clinical focus, the data were not analyzed until currently.

All patients meeting study criteria were eligible for the study and were approached for consent. Inclusion criteria consisted of the following:

Results

A total of 55 patients were enrolled in the study (Figure; available at www.jpeds.com); 29 patients received placebo and 26 iNO. Two patients randomized to iNO were withdrawn from the study as the result of premature termination of study gas. One patient that was randomized to receive placebo inadvertently received iNO and was evaluated as a part of the iNO cohort. There was no difference in age at time of enrollment (P = .14) and there is an equal distribution of primary diagnosis between

Discussion

We report the results of a prospective randomized blinded trial on the impact of iNO on outcomes in pediatric ARDS. We found that iNO led to a significant reduction in the duration of mechanical ventilation and to a significantly greater rate of ECMO-free survival. Previous studies of iNO in pediatric ARDS were either designed with or allowed for a crossover to iNO, precluding an analysis on the impact of iNO on outcomes in pediatric ARDS.10, 11

Studies in adult ARDS have not demonstrated

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  • Cited by (0)

    Supported by the Ikaria Corporation (formerly INO Therapeutics). The authors declare no conflicts of interest.

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