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 (1-3d, 1.5-2.4kg) were acutely instrumented to measure heart rate, systemic and pulmonary artery pressures, and pulmonary artery flow. After 2h of normocapnic hypoxia, animals were resuscitated with 100% oxygen for 1h followed by 21% oxygen for 3h. Intravenous hydrocortisone (1mg/kg) or saline was given in a blinded, randomized fashion 2h 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: 17.2-18.3mM), tachycardia and shock. Hydrocortisone did not affect systemic haemodynamics which recovered with reoxygenation, but it increased pulmonary artery pressure at 90-120min after administration (36±3 vs. 27±2 and 26±1mmHg 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.
Department of Paediatrics, University of Alberta, Canada.
Isabelle
I
Chapados
Tze-Fun
TF
Lee
Constance L
CL
Chik
Po-Yin
PY
Cheung
D000818:Animals; D000831:Animals, Newborn; D001237:Asphyxia / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006854:Hydrocortisone / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D000860:Hypoxia / Q000188:drug therapy* / Q000628:therapy; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D010102:Oxygen Inhalation Therapy / Q000379:methods; D011651:Pulmonary Artery / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D012151:Resuscitation / Q000379:methods; D013552:Swine; D013997:Time Factors
D010100:Oxygen; D006854:Hydrocortisone