Another outstanding lecture presented at the 11th World Congress Meeting in Berlin was by Dr. Eric Buchser, entitled: “CSF Dynamics and Implications.” I have heard Dr. Buchser present on the topic of drug distribution within the intrathecal space in the past, but this year’s presentation gave greater depth to the study of pharmacokinetics within the cerebral spinal fluid.
Dr. Buchser asserted that drug distribution occurs in two manners: 1) molecular diffusion and 2) the cardiovascular system affecting CSF flow. The anatomy of the intrathecal space also affects drug movement due to ligaments and nerves – which create turbulence and thereby affect flow secondary to hemodynamics.
It is my understanding, reaffirmed by Dr. Buchser and Dr. Yaksh, that there is not a true net CSF flow. This large body of water does circulate to some extent, but not like an active flowing river. One example described to me was: a river will flow into a large body of water – like a lake – and by another river at the other end of that lake, water will flow out. However, even with this inflow and outflow continually happening, the center of the lake experiences little to no movement. Hence, pharmaceuticals cannot traverse the entire length of the spinal cord due to fluid movement. I encourage everyone to read some of the work by Christopher Bernards who has studied the cerebrospinal fluid and distribution of baclofen and bupivacaine during intraspinal infusions in the pig model. In this study, Dr. Bernards demonstrated the drugs’ limited distribution beyond the catheter tip. (Anesthesiology 2006: 105: 169-78)
Dr. Buchser also stated that – pointing to current technology employed for intraspinal infusions – an increase in flow rates will not necessarily increase clinical effects. Preclinical in-vitro studies show that dramatic increases in flow rate will increase distribution and, therefore, clinical effects. However, Dr. Buchser expressed that current infusion devices cannot deliver these types of flow rates at this time. He and Dr. Saulino have suggested that bolus doses may increase clinical effects.
This subject has been of great significance to me because we are still learning more information as it relates to the pharmacokinetics of the intrathecal space. If interested, I encourage you to reach out to me regarding this subject, as I am always available for your calls.
This was just another truly fascinating lecture presented during one of the world’s greatest pain medicine conferences.
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