OBJECTIVE: We designed and conducted a randomized, double-masked, controlled multicenter study to determine whether inhaled nitric oxide (INO) in term and near-term infants with congenital diaphragmatic hernia (CDH) would reduce the occurrence of death and/or the initiation of extracorporeal membrane oxygenation (ECMO). PATIENTS AND METHODS: Infants of 34 weeks gestation or more, <14 days of age with CDH, without known structural heart disease, requiring assisted ventilation for hypoxemic respiratory failure with two oxygenation indices (OIs) of 25 or more at least 15 minutes apart, were eligible for this trial. Infants were centrally randomized and then received masked treatment with 20 ppm NO or 100% oxygen as control. Infants with less than a full response to 20 ppm NO (increase in PaO2 > 20 Torr) after 30 minutes were evaluated at 80 ppm NO/control study gas. RESULTS: The 28 control and 25 treated infants enrolled by the 13 participating centers were not significantly different at randomization for any of the measured variables including prerandomization therapies and initial OIs (45.8 +/- 16.3 for controls, 44.5 +/- 14.5 for INO). Death at <120 days of age or the need for ECMO occurred in 82% of control infants compared with 96% of INO infants (ns). Death occurred in 43% of controls and 48% of the INO group (ns), and ECMO treatment was used for 54% of control and 80% of INO-treated infants. There was no significant improvement in PaO2 (delta PaO2 7.8 +/- 19.8 vs 1.1 +/- 7.6 Torr, ns) nor significant reduction in OI (-2.7 +/- 23.4 vs 4.0 +/- 14.8, ns) associated with INO treatment. Mean peak nitrogen dioxide (NO2) concentration was 1.9 +/- 1.3 ppm and the mean peak methemoglobin was 1.6 +/- 0.8 mg/dL. No infant had study gas discontinued for toxicity. There were no differences between the control and INO groups for the occurrence of intracranial hemorrhage, specific grades of intracranial hemorrhage, periventricular leukomalacia, brain infarction, and pulmonary or gastrointestinal hemorrhages. CONCLUSIONS: Although the immediate short-term improvements in oxygenation seen in some treated infants may be of benefit in stabilizing responding infants for transport and initiation of ECMO, we conclude that for term and near-term infants with CDH and hypoxemic respiratory failure unresponsive to conventional therapy, inhaled NO therapy as used in this trial did not reduce the need for ECMO or death.
RCT Entities:
OBJECTIVE: We designed and conducted a randomized, double-masked, controlled multicenter study to determine whether inhaled nitric oxide (INO) in term and near-term infants with congenital diaphragmatic hernia (CDH) would reduce the occurrence of death and/or the initiation of extracorporeal membrane oxygenation (ECMO). PATIENTS AND METHODS: Infants of 34 weeks gestation or more, <14 days of age with CDH, without known structural heart disease, requiring assisted ventilation for hypoxemic respiratory failure with two oxygenation indices (OIs) of 25 or more at least 15 minutes apart, were eligible for this trial. Infants were centrally randomized and then received masked treatment with 20 ppm NO or 100% oxygen as control. Infants with less than a full response to 20 ppm NO (increase in PaO2 > 20 Torr) after 30 minutes were evaluated at 80 ppm NO/control study gas. RESULTS: The 28 control and 25 treated infants enrolled by the 13 participating centers were not significantly different at randomization for any of the measured variables including prerandomization therapies and initial OIs (45.8 +/- 16.3 for controls, 44.5 +/- 14.5 for INO). Death at <120 days of age or the need for ECMO occurred in 82% of control infants compared with 96% of INO infants (ns). Death occurred in 43% of controls and 48% of the INO group (ns), and ECMO treatment was used for 54% of control and 80% of INO-treated infants. There was no significant improvement in PaO2 (delta PaO2 7.8 +/- 19.8 vs 1.1 +/- 7.6 Torr, ns) nor significant reduction in OI (-2.7 +/- 23.4 vs 4.0 +/- 14.8, ns) associated with INO treatment. Mean peak nitrogen dioxide (NO2) concentration was 1.9 +/- 1.3 ppm and the mean peak methemoglobin was 1.6 +/- 0.8 mg/dL. No infant had study gas discontinued for toxicity. There were no differences between the control and INO groups for the occurrence of intracranial hemorrhage, specific grades of intracranial hemorrhage, periventricular leukomalacia, brain infarction, and pulmonary or gastrointestinal hemorrhages. CONCLUSIONS: Although the immediate short-term improvements in oxygenation seen in some treated infants may be of benefit in stabilizing responding infants for transport and initiation of ECMO, we conclude that for term and near-term infants with CDH and hypoxemic respiratory failure unresponsive to conventional therapy, inhaled NO therapy as used in this trial did not reduce the need for ECMO or death.
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