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Cerebrospinal fluid (CSF) is produced by the choroid plexus lining the ventricles at a rate of 15–30 mL/h, or approximately 500 mL/d in adults.46 Cerebrospinal fluid flows in a rostral to caudal direction and is resorbed through the arachnoid villi directly into the venous circulation. The estimated total volume of CSF in a healthy adult is between 130–150 mL, and 35 mL in infants.46,62,82

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For over 100 years, a variety of experimental and therapeutic xenobiotics have been delivered directly into the CSF.53,109 The most common current indications for intrathecal xenobiotic administration include analgesia, anesthesia, and treatment of spasticity or 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 may be attached to either an external or subcutaneous pump. Less commonly, substances are administered into a reservoir of an intraventricular shunt (Table SC2–1). 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 that the dilution of xenobiotics administered via a lumbar catheter is attributed to the outflow of CSF from the fourth ventricle.79 In a radiolabelled tracer study of 5 patients with lumbar catheters, individuals received intrathecally the hydrophilic radiolabeled diethylene triamine pentaacetic acid (111In- DTPA). Neuroimaging revealed a drop in concentration of the tracer as the fluid moved rostrally.55 The steady state lumbar to cervical concentration for hydrophilic xenobiotics is 4:1 with marked interindividual variability.79 Depending on the lipophilicity the xenobiotic reaches the brain within a few minutes to 1 hour. Patient position, and interindividual variations in lumbosacral CSF fluid volume may affect xenobiotic distribution and may account for the differences in the level of spinal anesthesia among patients administered the same local anesthetic dosages.44 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.44 In overdose or administration of xenobiotics unintended for intrathecal administration, distribution, resorption, and clinical effects may not follow predictable models.

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Table SC2–1. Xenobiotics Administered Intrathecally*

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