Eur J Pediatr (2011) 170:1495–1505 meconium-instilled piglets, pretreatment with dexametha- sone (1 h before meconium instillation) reduced pulmonary vascular resistance and lung edema, improved oxygenation and prevented ultrastructural changes of the lungs [30]. Similarly, the early administration of dexamethasone (30 min after meconium instillation) significantly reduced right-to-left pulmonary shunting, improved gas exchange and decreased ventilatory pressures in meconium-instilled rabbits compared to non-treated controls [50]. Furthermore, early dexamethasone decreased the neutrophil count in BAL fluid and reduced lung edema, meconium-induced tracheal hyperreactivity to histamine and concentrations of lipid and protein peroxidation products in the lung homogenate compared to controls [50, 55]. On the other side, the late administration of dexamethasone (1 h after meconium instillation) led to only non-significant improve- ment of oxygenation and had no effect on lung edema in piglets with MAS [30]. The results have clearly showed a better effect of GCs in early administration occurring before extensive tissue response to the meconium instillation. Considering time-related inflammatory changes in MAS, limitations of the treatment efficacy in late administration of GCs may be reduced by repetitive administration. It is known that the action of dexamethasone is fast, but of a short term. The half-life of dexamethasone in adults is 110– 190 min, with the biological half-life of 36–72 h [14, 74]. In newborns, the plasma half-life of dexamethasone is 150– 300 min and the biological half-life is between 36–54 h [47]. Therefore, in acute situations, repetitive administration every 2–4 h is recommended (data given by the producer, Dexamed, Medochemie, Cyprus). In meconium-instilled piglets, two-phase dexamethasone administration at 2 and 8 h after meconium instillation significantly improved gas exchange and lung compliance compared to controls [37]. In a rabbit model of MAS, the repetitive administration of dexamethasone 0.5 and 2.5 h after meconium instillation suppressed inflammation and enhanced gas exchange more effectively than a single dose administered 0.5 h after meconium [50, 52]. Similarly, in newborns with MAS, dexamethasone administered in gradually decreasing doses within maximally 9 days (at a dose of 0.5, 0.25 and 0.125 mg/kg/day, each administered for 3 days) decreased the oxygenation index and facilitated weaning from the ventilator [18]. Nevertheless, high doses of systemic GCs or their repetitive administration may exert various undesirable effects. Although the acute cardiovascular changes may be critical for neonates with meconium-induced lung injury, the side effects of repetitive GCs administration in MAS have not been investigated yet in a clinical study. In a rabbit model of MAS, the slow intravenous administration of one dose, but especially of two doses of dexamethasone, was associated with acute changes of blood pressure, heart rate and heart rate 1501 variability within 5 h of treatment [52, 54]. A detailed analysis of cardiovascular changes showed increased blood pressure, decreased heart rate, increased heart rate variability and a higher occurrence of cardiac arrhythmias particularly during and immediately after dexamethasone administration, while decreased heart rate and increased heart rate variability were observed until the end of the observation period (i.e. 5 h after the first dose of dexamethasone) [52, 54]. Budesonide is an inhalational GC used in the treatment of bronchial asthma, non-infectious rhinitis (including hay fever and other allergies) and nasal polyposis. Budesonide has high first-pass metabolism and its administration is associated with a lower incidence of systemic manifestations than with other GCs (fewer bone density losses and little influence on the hypothalamic–pituitary–adrenal axis) [3, 31]. In meconium-instilled rabbits, budesonide (Pulmicort, 0.25 mg/kg) was administered intratracheally 30 min after meconium instillation and then 2 h later using the inpulsion effect of high-frequency jet ventilation (inspiration time 20%). The treatment effectively alleviated inflammation, decreased lung edema formation and meconium-induced tracheal and lung smooth muscle hyperreactivity to hista- mine, improved gas exchange and decreased the oxidation injury of the lungs compared to non-treated controls [51]. In addition, intratracheal budesonide administration was associated with negligible acute cardiovascular effects [49] compared to dexamethasone [52, 54]. In 32 newborns with MAS, budesonide administered for a period of 7 days starting after 24 h of age shortened the period of oxygen delivery and duration of hospital stay and improved the radiological clearance of the lungs, while no serious adverse effects were found [4]. In another study [77, 78], budesonide was given in 17 newborns with MAS at a dose of 50 μg/kg/day, i.v., in two divided doses every 12 h for 7 days. Comparably to Basu et al. [4], budesonide shortened the duration of stay, oxygen dependence and X- ray of the lungs, decreased the levels of TNFα in tracheal aspirate and did not increase the incidence of sepsis. Local administration predisposes the inhalational GCs to be faster and of more potent action at the site of inflammation. Thanks to high lipophility, inhalational GCs (budesonide) have rapid direct effects on cells involved in airway inflammation including macrophages, eosinophils, T lymphocytes and airway epithelial cells [3]. In in vitro comparison of potency to reduce a release of IL-8 from airway epithelial cells, budesonide has shown ten-times- stronger activity than dexamethasone [59]. It corresponds well with our findings in the rabbit model of MAS, where intratracheal budesonide improved gas exchange and reduced lipid and protein peroxidation in the lung tissue more effectively compared to dexamethasone. In addition, budesonide reduced both tracheal and lung smooth muscle hyperresponsiveness to histamine, while dexamethasone