ABSTRACT
BACKGROUND: Surfactant is a well-established therapy for preterm neonates affected by respiratory distress syndrome (RDS). The goals of different methods of surfactant administration are to reduce the duration of mechanical ventilation and the severity of bronchopulmonary dysplasia (BPD); however, the optimal administration method remains unknown. This study compares the effectiveness of the INtubate-RECruit-SURfactant-Extubate (IN-REC-SUR-E) technique with the less-invasive surfactant administration (LISA) technique, in increasing BPD-free survival of preterm infants. This is an international unblinded multicenter randomized controlled study in which preterm infants will be randomized into two groups to receive IN-REC-SUR-E or LISA surfactant administration. METHODS: In this study, 382 infants born at 24+0-27+6 weeks' gestation, not intubated in the delivery room and failing nasal continuous positive airway pressure (nCPAP) or nasal intermittent positive pressure ventilation (NIPPV) during the first 24 h of life, will be randomized 1:1 to receive IN-REC-SUR-E or LISA surfactant administration. The primary outcome is a composite outcome of death or BPD at 36 weeks' postmenstrual age. The secondary outcomes are BPD at 36 weeks' postmenstrual age; death; pulse oximetry/fraction of inspired oxygen; severe intraventricular hemorrhage; pneumothorax; duration of respiratory support and oxygen therapy; pulmonary hemorrhage; patent ductus arteriosus undergoing treatment; percentage of infants receiving more doses of surfactant; periventricular leukomalacia, severe retinopathy of prematurity, necrotizing enterocolitis, sepsis; total in-hospital stay; systemic postnatal steroids; neurodevelopmental outcomes; and respiratory function testing at 24 months of age. Randomization will be centrally provided using both stratification and permuted blocks with random block sizes and block order. Stratification factors will include center and gestational age (24+0 to 25+6 weeks or 26+0 to 27+6 weeks). Analyses will be conducted in both intention-to-treat and per-protocol populations, utilizing a log-binomial regression model that corrects for stratification factors to estimate the adjusted relative risk (RR). DISCUSSION: This trial is designed to provide robust data on the best method of surfactant administration in spontaneously breathing preterm infants born at 24+0-27+6 weeks' gestation affected by RDS and failing nCPAP or NIPPV during the first 24 h of life, comparing IN-REC-SUR-E to LISA technique, in increasing BPD-free survival at 36 weeks' postmenstrual age of life. TRIAL REGISTRATION: ClinicalTrials.gov NCT05711966. Registered on February 3, 2023.
Subject(s)
Infant, Premature , Pulmonary Surfactants , Respiratory Distress Syndrome, Newborn , Female , Humans , Infant, Newborn , Airway Extubation/adverse effects , Bronchopulmonary Dysplasia/therapy , Continuous Positive Airway Pressure , Gestational Age , Intubation, Intratracheal , Multicenter Studies as Topic , Pulmonary Surfactants/administration & dosage , Randomized Controlled Trials as Topic , Respiratory Distress Syndrome, Newborn/therapy , Respiratory Distress Syndrome, Newborn/mortality , Time Factors , Treatment OutcomeABSTRACT
Epoprostenol has been the first effective treatment for severe pulmonary arterial hypertension. Epoprostenol is provided in vials for adult therapy. To our knowledge there are no reports on specific dilution protocols for epoprostenol in VLBW infants, when very small infusion rates are required. We describe the dilution protocol we applied to a preterm infant who was born at 30 weeks of gestational age with a weight of 1.000 g. Our dilution protocol keeps the recommended dilution ratios, and the required solution pH, for very small dosages of epoprostenol, using the same diluent vial. Our method allows a correct and safe administration of epoprostenol in VLBW infants.
Subject(s)
Antihypertensive Agents/administration & dosage , Epoprostenol/administration & dosage , Hypertension, Pulmonary/drug therapy , Antihypertensive Agents/adverse effects , Antihypertensive Agents/therapeutic use , Dose-Response Relationship, Drug , Epoprostenol/adverse effects , Epoprostenol/therapeutic use , Familial Primary Pulmonary Hypertension , Humans , Hydrogen-Ion Concentration , Infant, Newborn , Infant, Very Low Birth Weight , Male , Severity of Illness IndexABSTRACT
Endothelin receptor antagonism is an important therapeutic tool of pulmonary arterial hypertension (PAH). Bosentan was the first orally active, dual antagonist of endothelin receptors in human adults, and has been recently considered for children as well. However, little is known about bosentan treatment in children weighing less than 10 kg. We describe the use of bosentan concomitantly to epoprostenol in an infant weighing 3.5 kg and affected with severe bronchopulmonary dysplasia (BPD) and PAH. At 5 months old, when she presented subsystemic PAH secondary to severe BPD, she was treated with oxygen, digoxin and diuretics. At 8 months old, due to severe PAH not responsive to 100% oxygen, high frequency oscillatory ventilation (HFOV) and nitric oxide (NO), we started epoprostenol and bosentan. Bosentan dose was doubled at 9 months old, when HFOV and NO were slowly discontinued due to improved oxygenation index. Regular echocardiographic measurements of systolic right ventricular pressure were recorded by the method of tricuspidal atrio-ventricular gradient. A four-month combined epoprostenol and bosentan treatment decreased systolic right ventricular pressure from 68% to 40% of the systemic level, till its normalization at 11 months old. Later, when bosentan and epoprostenol were discontinued and sildenafil was started, severe PAH was reported again. Our patient died due to septic shock and refractory hypoxia at 14 months old.
