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Histological changes following epidural injection of midazolam in the neonatal rabbit
1Department of Anaesthesiology, Istanbul University Cerrahpaşa Medical Faculty, Turkey.
Abstract:
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.
Insights
Epidural midazolam can cause spinal cord neurotoxicity in neonatal rabbits, similar to acidic saline. These findings suggest avoiding epidural midazolam in neonates due to potential adverse histological effects.
Area of Science:
- Neuroscience
- Toxicology
- Histology
Background:
- Midazolam exhibits antinociceptive properties via intrathecal and epidural administration.
- Limited neurotoxicity data exists for neonatal spinal cord exposure to epidural midazolam.
Purpose of the Study:
- To investigate the electron microscopic (EM) histological effects of epidural midazolam on the neonatal rabbit spinal cord.
Main Methods:
- Neonatal rabbits received epidural injections of saline, acidic saline (pH 3.9), or midazolam (250 µg/kg).
- Spinal cord tissues were examined using electron microscopy on days 2 and 7 post-injection.
- Histological changes were evaluated in control and experimental groups.
Main Results:
- Control group showed normal spinal cord histology.
- Acidic saline and midazolam groups exhibited dose-dependent neurotoxic effects.
- Observed neurotoxicity included vacuolar degeneration, neurofilament disruption, myelin sheath damage, and cellular membrane lysis.
Conclusions:
- Epidural midazolam induces neurotoxic effects in the neonatal spinal cord, comparable to acidic saline.
- The acidic nature of commercially available midazolam preparations may contribute to observed toxicity.
- Epidural administration of midazolam in neonates should be approached with caution and potentially avoided.