Effect of continuous morphine infusion on hypoxic-ischaemic brain damage of neonatal rats

Abstract

Opioids are commonly administered to critically ill neonates and infants for general anaesthesia and sedation. However, the clinical safety of these drugs, especially the effects on hypoxic-ischaemic damage of the developing brain, has not been well investigated. The present study was therefore conducted to investigate the effects of continuous morphine infusion on brain damage after hypoxic-ischaemic insults in neonatal rats. Seven-day-old Sprague-Dawley rats were subjected to left common carotid artery ligation followed by a 90-min exposure of 8% oxygen. The rats were administered morphine (0.1, 0.3 or 1 mg/kg/h) or saline continuously for 72 h using osmotic minipumps. Seven days later, the rats were weighed and their brains were morphologically categorized into groups based on the following grades: 0=normal, 1=mild atrophy, 2=moderate atrophy, 3=atrophy with cystic cavitation <3 mm and 4=cystic cavitation >3 mm. For histological assessment, the ratio of the surviving neurons (ipsilateral/contralateral) was calculated in the cornu ammonis fields, CA1 and CA3, and the dentate gyrus (DG). One week after recovery (P14), the rats in the 1 mg/kg/h group showed significantly poorer weight gain compared with the other groups. However, the morphological score of the brains and the ratio of the surviving neurons in the CA1, CA3 and DG were similar among the groups. Our results indicate that continuous administration of morphine does not worsen brain damage 7 days after hypoxic-ischaemic insults in neonatal rats.