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Updated: Aug 8, 2026

Delivery of Therapeutic Agents Through Intracerebroventricular (ICV) and Intravenous (IV) Injection in Mice
Published on: October 3, 2011
[Neurotoxicity of intrathecally administrated agents]
1Service d'anesthésie-réanimation chirurgicale, Hôtel-Dieu, Nantes, France.
Abstract:
Spinal anaesthetics can induce histopathologic lesions and regional haemodynamic alterations in the spinal cord. There are numerous causes of neurologic lesions, including direct trauma of the spinal cord and nerve roots during puncture or catheter insertion, compromised spinal cord perfusion and direct neurotoxic effect. Histopathologic lesions are localized either in meninges (meningitis or arachnoiditis) or in neuraxis (myelitis or axonal degeneration). Neurotoxicity can result from decrease in neuronal blood supply, elicited by high concentrations of the solutions, long duration exposure to local anaesthetics, and the use of adjuvants. They have been implicated in the occurrence of cauda equina syndrome after continuous spinal anaesthesia using hyperbaric solution of lidocaine and tetracaine given through small diameter catheters. Selective spinal analgesia is induced by spinal opioids without motor blockade except for meperidine. Complications occurred in patients after high doses of morphine, which were related to one of its metabolites, morphine-3-glucuronide. Preservative-free opioid solutions are to be preferred for spinal anaesthesia. There is no report of neurotoxicity neither in animal studies, nor in humans, using spinal clonidine. In order to reduce the incidence of neurotoxicity, some safety rules should be followed. The lowest efficient dose of local anaesthetics must be given. Incomplete blockade should not necessarily lead to a reinjection. Large volume of hyperbaric lidocaine or repeated injections of such solutions must be avoided as well as preservative-containing solutions. The administration of new compounds by the spinal route must be supported by data of spinal neuropharmacology and the lack of neurotoxicity must have been previously checked with animal studies.
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