Role of Catheter's Position for Final Results in Intrathecal Drug Delivery. Analysis Based on CSF Dynamics and Specific Drugs Profiles

Abstract

Intrathecal drug delivery is an effective and safe option for the treatment of chronic pathology refractory to conventional pain therapies. Typical intrathecal administered drugs are opioids, baclofen, local anesthetics and adjuvant medications. Although knowledge about mechanisms of action of intrathecal drugs are every day more clear many doubt remain respect the correct location of intrathecal catheter in order to achieve the best therapeutic result. We analyze the factors that can affect drug distribution within the cerebrospinal fluid. Three categories of variables were identified: drug features, cerebrospinal fluid (CSF) dynamics and patients features. First category includes physicochemical properties and pharmacological features of intrathecal administered drugs with special attention to drug lipophilicity. In the second category, the variables in CSF flow, are considered that can modify the drug distribution within the CSF with special attention to the new theories of liquoral circulation. Last category try to explain inter-individual difference in baclofen response with difference that are specific for each patients such as the anatomical area to treat, patient posture or reaction to inflammatory stimulus. We conclude that a comprehensive evaluation of the patients, including imaging techniques to study the anatomy and physiology of intrathecal environment and CSF dynamics, could become essential in the future to the purpose of optimize the clinical outcome of intrathecal therapy.

Efficacy and safety of oral baclofen in the management of spasticity: A rationale for intrathecal baclofen

“…Increasing the dosage does not significantly increase the concentration at the site of action in the CSF, but instead results in high plasma levels (47,(61)(62)(63). As a result, spasticity is often not well controlled, leading to a significant loss of function with continued pain and care-related problems (64), combined with side-effects that may be intolerable (15,47). Thus, there is a need for action in patients who fail to respond adequately to oral baclofen.…”

“…Although widely used, baclofen is mainly water soluble and so does not readily cross the blood-brain barrier (14). As a result, patients may require a high dose to treat their spasticity effectively, which can cause intolerable side-effects (15). As an alternative, baclofen can be delivered directly to the cerebrospinal fluid (CSF) in the intrathecal space, bypassing the blood-brain barrier entirely.…”

Intrathecal baclofen pump implantation for complex regional pain syndrome in a patient with a spinal cord stimulator: consideration about optimal location of intrathecal catheter tip - A case report -

“…Jose et al [15] suggested that drug features, CSF dynamics, and patient characteristics should be considered when determining the location of the intrathecal catheter. In conclusion, this case report suggests that intrathecal baclofen administration provides satisfactory pain relief in CRPS patients with chronic intractable neuropathic pain not improved by an SCS.…”

Usefulness of Imaging for Intrathecal Drug Delivery Systems: An update

“…Limited intrathecal diffusion has been proven in animal models, computer simulations and in humans using different flow-rate models similar to those delivered by programmable IDDS (16,23,24). Current guidelines recommend placing the catheter tip close to the target receptors of the spinal segment(s) associated with the dermatome of the primary pain generator (25).…”