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  • Updated 03.20.2021
  • Released 02.08.2001
  • Expires For CME 03.20.2024

Intrathecal administration of drugs

Introduction

Overview

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. Several other indications are discussed, including intrathecal chemotherapy for carcinomatous meningitis and chronic pain.

Key points

• 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 route of drug administration is well established in anesthesia and pain management.

• It provides a route for drug transport deep into the brain via CSF.

• Guided by drug-specific kinetics of tissue uptake, which determine the speed of drug dispersion, it is possible to administer intrathecal therapy personalized to a patient’s needs.

• This route enables a large molecule drugs such as antisense oligonucleotides to be delivered to the CNS by bypassing the blood-brain barrier, eg, nusinersen for spinal muscular atrophy.

• Systemic side-effects of several drugs such as opioids can be avoided if they are given in smaller doses for localized action in the nervous system.

• An adverse effect of intrathecal therapy is drug-induced aseptic or chemical meningitis due to direct irritation of the meninges by the drug.

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 (08). Intrathecal introduction of contrast material for myelography was first performed in 1921 by Athanase Sicard, a Parisian neurologist (31). 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 1 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 (05; 22).

The first implantable pump for intrathecal and intraventricular injection of morphine for the treatment of cancer pain was described in 1978 (21). 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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