Chapter SC7: Intrathecal Administration of Xenobiotics

INTRODUCTION

Cerebrospinal fluid (CSF) is produced by the choroid plexus that lines the cerebral ventricles at a rate of 15 to 30 mL/h, or approximately 500 mL/day in adults.⁵⁷ Cerebrospinal fluid flows in a rostral to caudal direction and is reabsorbed through the arachnoid villi directly into the venous circulation. The estimated total volume of CSF is 130 to 150 mL in healthy adults and 35 mL in infants.^57,74,99

For more than 100 years, a variety of experimental and therapeutic xenobiotics have been delivered directly into the CSF^64,127 (Table SC7–1). The most common current indications for intrathecal administration include the instillation of analgesics or anesthetics and the treatment of spasticity or central nervous system (CNS) neoplasms. The clinical advantages of this route of administration include targeted delivery and lower medication dosages with fewer systemic effects. Medications are usually administered via a spinal needle or an indwelling intrathecal catheter. Catheters can be attached to either an external or subcutaneous pump. Less commonly, medications are administered into a reservoir of an intraventricular shunt. The distribution of intrathecal xenobiotics is determined by a variety of factors. Some authors speculate that the xenobiotic movement is often attributed to both diffusion and convection, and they suggest that the dilution of xenobiotics administered via a lumbar catheter is attributed to the outflow of CSF from the fourth ventricle.⁹² In a radiolabeled tracer study of 5 patients with lumbar catheters, individuals received the hydrophilic radiolabeled diethylene triamine pentaacetic acid (¹¹¹In-DTPA) intrathecally. Neuroimaging revealed a drop in concentration of the tracer as the fluid moved rostrally.⁶⁶ The steady-state lumbar to cervical concentration for hydrophilic xenobiotics is 4:1 with marked interindividual variability.⁹⁶ Depending on the lipophilicity, the xenobiotic reaches the brain within a few minutes to 1 hour. Patient position and interindividual variations in lumbosacral CSF volume affect xenobiotic distribution and account for the differences in the level of spinal anesthesia among patients administered the same local anesthetic dosages.⁵⁵ Baricity, which is the ratio of the specific gravity of the xenobiotic to the specific gravity of CSF at 98.6°F (37°C), is also a consequential variable. Hyperbaric xenobiotics typically distribute in accordance with gravitational forces.⁵⁵ However, in overdose or administration of xenobiotics unintended for intrathecal administration, distribution, reabsorption, and clinical effects are unpredictable.