Several drugs that act on the nervous system are administered by the intrathecal route. The main application is in anesthesia and management of pain. This route has the advantage of bypassing the blood-brain barrier for drugs with poor penetration into the central nervous system, and an intrathecal antisense drug, nusinersen, has been approved for the treatment of spinal muscular atrophy. A number of other indications are discussed, including intrathecal chemotherapy for carcinomatous meningitis and chronic pain.
• Intrathecal drug administration is the introduction of a therapeutic substance into the cerebrospinal fluid by injection into the subarachnoid space of the spinal cord to bypass the blood-brain barrier.
• The main indications are for anesthesia and pain management.
• Adverse effects associated with this route of administration and complications of the devices used for this purpose should be noted.
Historical note and terminology
Intrathecal drug administration means the introduction of a therapeutic substance by injection into the subarachnoid space of the spinal cord. This is a strategy to bypass the blood-brain barrier by using an alternate route of delivery. The first perforation of subarachnoid space by lumbar puncture was made in 1885 to administer cocaine for anesthesia (Corning 1885). Intrathecal introduction of contrast material for myelography was first performed in 1921 by Athanase Sicard, a Parisian neurologist (Sicard and Forestier 1921). Sicard had originally injected lipiodol into the lumbar muscles for the treatment of backache and sciatica. He knew the radio-opaque nature of lipiodol, and when one of his assistants accidentally injected it into the spinal subarachnoid space without any ill effects, he noted the movements of the contrast medium on x-rays. Myelography was, thus, introduced in clinical practice. Neurologic injury, ranging from transient radiculopathy to paraplegia, has been a dreaded complication of spinal and epidural injection from the earliest days of these 2 techniques. Early reports of neurologic complications include oculomotor palsy, cauda equina syndrome, and paraplegia (Blanluet and Caron 1907; Lusk 1911).
The first implantable pump for intrathecal and intraventricular injection of morphine for the treatment of cancer pain was described in 1978 (Lazorthes et al 1991). Although the most frequent use of intrathecal route is for administration of anesthetics, the focus of this article is on introduction of therapeutic substances into the intrathecal space of the spinal cord.
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