Despite the fact that some studies reported a modulating effect of treatment regimens in favor of higher-dosage regimens on the incidence of BPD and neurodevelopmental impairment, recommendations on the optimal type of corticosteroid, the optimal dosage, or the optimal timing of initiation for the prevention of BPD in preterm infants cannot be made based on current level of evidence. A well-designed large RCT is urgently needed to establish the optimal systemic postnatal corticosteroid dosage regimen.

aaPersistent pulmonary hypertension (PPH) is a clinical syndrome, characterized by a sustained elevation of the pulmonary vascular resistance with a right-to-left shunt across the ductus arteriosus and/or the foramen ovale, causing severe hypoxaemia. Although generally associated with diseases of term newborns PPH has been increasingly described in preterm infants as well [1]. Inhaled nitric oxide (iNO) has been described as an effective selective pulmonary vasodilator improving oxygenation in newborns including preterm infants. However, concern over iNO relates to its potential toxicity and to difficulties in developing safe and effective delivery systems. Intravenous prostacyclin (epoprostenol) is a potent vasodilator in PPH [2]. Nevertheless, its effect on systemic vasculature and on pulmonary vessels of nonventilated areas limits its clinical application. Recently, aerosolized prostacyclin has been reported both in clinical and experimental settings to be a selective pulmonary vasodilator without side-effects on the systemic vasculature [3][4][5]. No human data on topical epoprostenol-related toxicity are available. In an animal study no signs of acute pulmonary toxicity were shown from prostacyclin inhalation [6]. We here describe the effect of endotracheal instillation of prostacyclin on oxygenation and haemodynamics in four preterm infants with severe pulmonary hypertension. Patients and methodsThe patients' underlying diseases were hyaline membrane disease (patients 1-3) and septicaemia caused by Escherichia coli (patient 4). Demographic data are listed in table 1. All patients had an arterial oxygen tension (Pa,O 2 )/ fraction of inspired oxygen (FI,O 2 ) ratio <70 despite optimum ventilator settings during at least 6 h. Oxygenation was monitored using pre-and postductal transcutaneous pulse oximetry and a pre-and/or postductal indwelling arterial catheter. The variables measured and calculated were the Pa,O 2 /FI,O 2 , the oxygenation index (OI; ((FI,O 2 × mean airway pressure)/ Pa,O 2 ) × 100) and mean systemic arterial blood pressure (MAP). Patients were only enrolled after informed consent was obtained from the parents. In all infants the presumptive diagnosis of persistent pulmonary hypertension was confirmed with air-contrast echocardiography showing a right-to-left shunt across the ductus arteriosus and/or the foramen ovale. The epoprostenol, dissolved in glycine buffer (Flolan®, GlaxoWellcome B.V., Zeist, the Netherlands), was diluted with saline (NaCl 0.9%) to a concentration of 50 ng·mL -1 . The pH of this solution was 10.3. This epoprostenol solution of 50 ng·mL -1 was instilled as a bolus of 1 mL·kg -1 endotracheally through a catheter reaching the distal end of the endotracheal tube. Endotracheal instillation of prostacyclin in preterm infants with persistent pulmonary hypertension. A.P.M.C. De Jaegere, J.N. van den Anker. ©ERS Journals Ltd 1998. ABSTRACT: Does endotracheal instilled prostacyclin (epoprostenol) improve oxygenation in preterm infants with persistent pulmonary hypertension?Fo...

Mixing a nitrogen/nitric oxide gas mixture 20 cm before the Y-connector results in an increase of the mean nitric oxide concentration with increasing ventilator rates. This phenomenon does not occur with the nitrogen/nitric oxide gas mixture mixed at the inlet of the humidifier, using a ventilator with a throughout constant flow at the inspiratory outlet of the ventilator. The fluctuations of the main ventilator circuit flow result in changing ratios of nitrogen/nitric oxide gas mixture and the ventilator gas flow. We speculate this changing flow ratio produces the increase in mean nitric oxide concentration within the ventilatory circuit. To ensure a constant concentration of nitric oxide by blending a nitrogen/nitric oxide gas mixture in the ventilator circuit of a continuous flow ventilator, the site of injection of the nitrogen/nitric oxide gas mixture should be at the point where ventilator circuit flow fluctuations are minimal.

Introduction: Inhaled nitric oxide ([NO) is a selective pulmonary vasodilator that is rapidly inactivated compared to intravenous vasodilators. These qualities make [NO an attractive agent for the treatment of pulmonary hypertension (PHTN). The efficacy of [NO has been studied in persistent fetal circulation, acute respiratory distress syndrome (ARDS), and congenital heart disease (CHD). Potential adverse effects of INO include: nitrogen dioxide (NOS) toxicity, rnethemoglobinemia, and platelet dysfunction. Our objective was to evaluate the safety of INO in pediatric patients (pts). Methods: Pediatric pts. with PHTN from ARDS or CHD were studied under an established, approved protocol conforming to FDA guidelines for an investigational new drug. Informed consent was obtained for each child prior to treatment. INO was sequentially titrated from 10 parts per million (ppm) to 20, 40, 60, and 80 ppm at ten minute intervals. Parameters monitored before and during therapy included nitric oxide (NO) and NOS concentrations (cone.), mean arterial blood pressure (MAP), and percent methemoglobin (MHG). NO and NO 2 levels were continuously monitored using an inline Drdger electrochemical detection device. MAP was continuously measured with an indwelling arterial catheter. MHG was measured by co-oximetry. A MHG level a 5% or NO2 cone. a 5 ppm were considered adverse effects by study criteria. Pretreatment MAP was compared to MAP at 40 and 80 ppm INO using paired t-tests. A p value < 0.05 was considered statistically significant. Results: Thirty-two mechanically ventilated children with PHTN (16 with ARDS, 16 with CHD) were studied. Five pts. were treated following cardiopulmonary bypass. Mean age was 38.1 months (range I day -201 months). Pretreatment MAP was 66.3 mmHg (range 35 -98 mmHg); MAP at 40 ppm INO was 65.7 mmHg (range 36-105 mmHg; p =0.48); MAP at 80 ppm INO was 70 mmHg (range 46-102 mmHg (N=29); p=0.5). Two asymptomatic pts. had MHG levels a 5% while receiving continuous [NO therapy at 80 ppm (I neonate, MHG 6%; 3 year old, MHG 5.7%). No other patients had MHG levels x 5%. Twenty-five children received continuous INO therapy with a mean duration of 105 hours (range of 6.2-661.5 hours). Clinical bleeding problems were not observed in any pts, treated with 1140. NO2 levels did not exceed 5 ppm. Conclusion: Clinically significant adverse effects from INO were not observed, although two asymptomatic pts. had MHG levels i 5%. No treatment for elevated MHG levels was required other than decreasing the [NO cone. Methemoglobinemia is potentially a greater risk for the neonatal population because they have decreased methemoglobin reductase activity. In the acute setting, [NO appears to be a safe form of therapy for pediatric pts. with PHTN from ARDS or CHD in cone, up to 80 ppm. Further investigation is needed to determine if there are any long term effects from INO therapy in pediatric pts.