INHALED NITRIC-OXIDE AND HYPOXIC RESPIRATORY-FAILURE IN INFANTS WITH CONGENITAL DIAPHRAGMATIC-HERNIA

Objective. We designed and conducted a randomized, double-masked, cont rolled multicenter study to determine whether inhaled nitric oxide (IN O) in term and near-term infants with congenital diaphragmatic hernia (CDH) would reduce the occurrence of death and/or the initiation of ex tracorporeal membrane oxygenation (ECMO). Patients and Methods. Infant s of 34 weeks gestation or more, <14 days of age with CDH, without kno wn structural heart disease, requiring assisted ventilation for hypoxe mic respiratory failure with two oxygenation indices (OIs) of 25 or mo re at least 15 minutes apart, were eligible for this trial, Infants we re 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>Torr) after 30 minutes were evaluated a t 80 ppm NO/control study gas. Results. The 28 control and 25 treated infants enrolled by the 13 participating centers were not significantl y different at randomization for any of the measured variables includi ng prerandomization therapies and initial OIs (45.8 +/- 16.3 for contr ols, 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 infa nts (ns). Death occurred in 43% of controls and 48% of the INO group(n s), and ECMO treatment was used for 54% of central and 80% of INO-trea ted 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. Mea n 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 ga s discontinued for toxicity. There were no differences between the con trol and INO groups far the occurrence of intracranial hemorrhage, spe cific grades of intracranial hemorrhage, periventricular leukomalacia, brain infarction, and pulmonary or gastrointestinal hemorrhages. Conc lusions. Although the immediate short-term improvements in oxygenation seen in some treated infants may be of benefit in stabilizing respond ing 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 t his trial did not reduce the need for ECMO or death.