Bozkurt P, Tunali Y, Kaya G, Okar I
Department of Anaesthesiology, Istanbul University Cerrahpaşa Medical Faculty, Turkey.
Paediatr Anaesth. 1997;7(5):385-9. doi: 10.1046/j.1460-9592.1997.d01-107.x.
Midazolam can produce antinociceptive effects when used via intrathecal or epidural routes. Neurotoxicity studies are scanty especially for neonates. The aim of this study was to carry out electron microscopic (EM) examinations in the neonatal rabbit to determine the histological effects of epidural midazolam on spinal cord. Twenty white New Zealand neonatal rabbits were randomly assigned to three groups receiving single dose of 0.9% saline (Group I; Control, n = 4), 0.9% saline titrated to pH = 3.9 by addition of hydrochloric acid (Group II; n = 6), midazolam 250 micrograms.kg-1 (Group III; n = 12) epidurally. Half of each group were sacrificed on the second day and the remainder on the seventh day and spinal cord sections were evaluated by EM. Control group displayed normal histology on grids. Group II and II showed a variable degree of neurotoxic effects such as degeneration of vacuoles, cytoplasm and neurofilaments, disruption of myelin sheaths, lysis of cell membranes, perivascular oedema, pyknosis of nuclei. The toxic effects of acidic saline and midazolam are similar, in view of these results the epidural use of acidic midazolam (commercially available preparations) in neonates should be avoided.
咪达唑仑经鞘内或硬膜外途径使用时可产生抗伤害感受作用。尤其是对于新生儿，神经毒性研究较少。本研究的目的是对新生兔进行电子显微镜（EM）检查，以确定硬膜外给予咪达唑仑对脊髓的组织学影响。将20只白色新西兰新生兔随机分为三组，分别硬膜外给予单剂量的0.9%生理盐水（I组；对照组，n = 4）、通过添加盐酸滴定至pH = 3.9的0.9%生理盐水（II组；n = 6）、250微克·千克-1的咪达唑仑（III组；n = 12）。每组一半在第二天处死，其余在第七天处死，脊髓切片通过EM评估。对照组在电镜下显示正常组织学。II组和III组显示出不同程度的神经毒性作用，如空泡、细胞质和神经丝变性、髓鞘破坏、细胞膜溶解、血管周围水肿、核固缩。鉴于酸性生理盐水和咪达唑仑的毒性作用相似，因此应避免在新生儿中硬膜外使用酸性咪达唑仑（市售制剂）。
