title: The neurotoxic effects of intrathecal midazolam and neostigmine in rabbits.
abstract: In parallel with improvements in understanding pain neurophysiology, many chemicals have recently been investigated for spinal anaesthesia and analgesia. However, studies discussing the effects of these drugs on neural tissue indicate that knowledge about some aspects of neurotoxicity is limited. Forty-nine New Zealand albino rabbits, weighing 2.2 +/- 0.2 kg, were randomly assigned to seven groups of seven animals each. Single dose groups received intrathecally through the atlantooccipital membrane 0.9% saline 1.5 ml; midazolam 100 microg/kg (low dose midazolam group) or 500 microg/kg (high dose midazolam group); neostigmine 10 microg/kg (low dose neostigmine group) or 50 microg/kg (high dose neostigmine group). Two groups had seven days of repeated dosing with either midazolam 100 microg/kg/day (repeat midazolam group) or 10 microg/kg/day neostigmine (repeat neostigmine group). The animals were sacrificed on day 8, and two spinal cord sections from the fourth cervical level and fourth lumbar level were removed and prepared for histopathological study. Transmission electron microscopic evaluations were performed on transverse spinal cord sections by a neuropathologist blinded to the group allocation. Twenty myelinated axons and neurones in the cervical and lumbar sections were investigated for the histopathological study. This study indicates that midazolam and neostigmine have different neurotoxic effects that depend on the dose and the repetition of dosing when these drugs are administered intrathecally.
authors.affiliation: Department ofAnesthesia, Ankara University Medical Faculty, Ankara, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Demirel
authors.forename: H C
authors.initials: HC
authors.lastname: Ugur
authors.forename: H
authors.initials: H
authors.lastname: Dolgun
authors.forename: G
authors.initials: G
authors.lastname: Kahilogullari
authors.forename: M E
authors.initials: ME
authors.lastname: Sargon
authors.forename: N
authors.initials: N
authors.lastname: Egemen
authors.forename: Y
authors.initials: Y
authors.lastname: Kecik
mesh_terms: D000704:Analysis of Variance; D018686:Anesthetics, Intravenous / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000648:ultrastructure; D001794:Blood Pressure / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000009:adverse effects / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D007278:Injections, Spinal; D008854:Microscopy, Electron; D008874:Midazolam / Q000009:adverse effects / Q000494:pharmacology*; D009388:Neostigmine / Q000009:adverse effects / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure; D011817:Rabbits; D012965:Sodium Chloride / Q000008:administration & dosage; D013116:Spinal Cord / Q000187:drug effects* / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D018686:Anesthetics, Intravenous; D002800:Cholinesterase Inhibitors; D009388:Neostigmine; D012965:Sodium Chloride; D008874:Midazolam