Effects of buoyancy on the dispersion of drugs released intrathecally in the spinal canal.

Abstract

This paper investigates the transport of drugs delivered by direct injection into the cerebrospinal fluid (CSF) that fills the intrathecal space surrounding the spinal cord. Because of the small drug diffusivity, the dispersion of neutrally buoyant drugs has been shown in previous work to rely mainly on the mean Lagrangian flow associated with the CSF oscillatory motion. Attention is given here to effects of buoyancy, arising when the drug density differs from the CSF density. For the typical density differences found in applications, the associated Richardson number is shown to be of order unity, so that the Lagrangian drift includes a buoyancy-induced component that depends on the spatial distribution of the drug, resulting in a slowly evolving cycle-averaged flow problem that can be analysed with two-time scale methods. The asymptotic analysis leads to a nonlinear integro-differential equation for the spatiotemporal solute evolution that describes accurately drug dispersion at a fraction of the cost involved in direct numerical simulations of the oscillatory flow. The model equation is used to predict drug dispersion of positively and negatively buoyant drugs in an anatomically correct spinal canal, with separate attention given to drug delivery via bolus injection and constant infusion.