Hydrocortisone administration increases pulmonary artery pressure in asphyxiated newborn piglets reoxygenated with 100% oxygen

In severely asphyxiated neonates developing vasopressor-resistant shock, hydrocortisone is commonly used to improve perfusion. However, its acute haemodynamic effects in asphyxiated neonates are largely unknown. In a swine model of neonatal asphyxia, effects of hydrocortisone on systemic and pulmonary circulations were examined. Piglets (1–3 d, 1.5–2.4 kg) were acutely instrumented to measure heart rate, systemic and pulmonary artery pressures, and pulmonary artery flow. After 2 h of normocapnic hypoxia, animals were resuscitated with 100% oxygen for 1 h followed by 21% oxygen for 3 h. Intravenous hydrocortisone (1 mg/kg) or saline was given in a blinded, randomized fashion 2 h after reoxygenation (n = 6/group). Haemodynamic parameters, blood gases, plasma cortisol, as well as levels of endothelin-1, nitrite/nitrate, nitrotyrosine, matrix metalloproteinases-2 and -9 in the lung were analysed. Severe hypoxia caused metabolic acidosis (mean pH: 6.91–6.97, mean plasma lactate: 17.2–18.3 mM), tachycardia and shock. Hydrocortisone did not affect systemic haemodynamics which recovered with reoxygenation, but it increased pulmonary artery pressure at 90–120 min after administration (36 ± 3 vs. 27 ± 2 and 26 ± 1 mm Hg for hypoxia–reoxygenation control and sham-operated piglets, respectively, P < 0.05). In the lung tissue, hydrocortisone significantly increased endothelin-1 and nitrite/nitrate levels, but had no effect on nitrotyrosine. Further, it decreased lung matrix metalloproteinase-9, but not matrix metalloproteinase-2, activity, which were both elevated with hypoxia–reoxygenation. It is most likely that the increase in pulmonary artery pressure observed after hydrocortisone treatment was associated with increased endothelin-1 level in the lung. Our findings caution the use of hydrocortisone as a first-intention treatment of shock in asphyxiated neonates.