Effects of midazolam on hypoxic-ischemic brain injury in neonatal piglets / 中华麻醉学杂志

ABSTRACT

Objective To investigate the effects of midazolam on hypoxic-ischemic (HI) brain injury in neonatal piglets.Methods Twenty-four newborn male piglets 3-7 days old weighing 1.8-3,0 kg were randomly divided into 3 groups ( n = 8 each) sham group (group S), HI + normal saline group (group HI-S) and HI + midasolam group (group HI-M). The animals of group HI-S and HI-M were subjected to 7 min of hypoxia, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation. At 3 h after restoration of spontaneous circulation (ROSC), animals received i.v. infusion of fentanyl at a rate of 10-30 μg·kg-1·h-1 and pancuroniumat a rate of 0.1-0.2 mg·kg-1·h-1 from 3 h after ROSC to 24 h after ROSC to maintain the anesthesia. In addition, midazolam at a rate of 0.05 mg·kg-1·h-1 wee infused simultaneously until 24 h after ROSC in HI-M group, while the equal volume of normal saline was infused instead in group HI-S and S. Arterial blood samples were taken before hypoxia (baseline), and at 37 min of hypoxia, 5 min of air inspiration, 5 min of asphyxia and 6, 12, and 24 h after ROSC for blood gas analysis, and MAP was monitored at the each time point. Neurological behavior was assessed and scored (NBS) at 48, 72, 96 and 240 h after ROSC. Brains were removed at 10 h after ROSC, the remaining viable neurons in putamen and candate nucleus were counted and the density of viable neurons was determined using light microscopic examination. Results PaO2 was significantly decreased during hypoxia-eephyxia, and PaCO2 was significantly increased, while pH value and MAP were significantly decreased at 5 min of asphyxia in group HI-S and HI-M compared with group S and the baseline (P < 0.05).There were no significant differences in MAP and arterial blood gas analysis at the each time point between group HI-S and HI-M ( P > 0.05). The density of viable neurons in putamen and caudate nucleus was significantly lower, and NBS at 48-96 h after BOSC significantly higher in group HI-S and HI-M than in group S ( P < 0.05). The density of viable neurons in putamen and caudate nucleus was significantly higher and NBS at 72 and 96 h after ROSC significantly lower in group HI-M than in group HI-S ( P < 0.05). Conclusion Midazolam used at the early stage of cardiopulmonary resuscitation can attenuate HI brain injury in neonatal piglets.