Paediatric Anaesthesia 1997 7: 385–389 Histological changes following epidural injection of midazolam in the neonatal rabbit P. BOZKURT * , YUSUF TUNALI * , GU ¨ NER KAYA * AND IMER OKAR† *Department of Anaesthesiology, Istanbul University Cerrahpas ¸a Medical Faculty, Istanbul, Turkey †Department of Histology, Marmara University Faculty of Medicine, Istanbul, Turkey Summary 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 g·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. Keywords: neonate; analgesic technique: epidural; midazolam: neurotoxicity Introduction axonal degeneration, oedema, necrosis, arachnoiditis and vascular changes. Such reactions may progress Spinal anaesthesia for high risk neonates and caudal slowly (3). Various drugs are being evaluated for local analgesic or narcotics for pain relief in children intrathecal or epidural routes in adults in order to are increasingly popular (1,2). However, the local minimize the motor effects of local anaesthetics or effects on the developing spinal cord are unknown. respiratory depression and urinary retention from The intrathecal and epidural administration of a drug opioids. Several study groups report that the epidural may produce toxic reactions such as demyelination, administration of midazolam has antinociceptive effects on visceral and somatic pain in man despite various conflicting reports on neurotoxicity of this Correspondence to: Pervin Bozkurt, Atako ¨y 5, Kısım A7 Blok D 40, 34750 Istanbul, Turkey. drug (4,5). 385  1997 Blackwell Science Ltd