Fluid mechanics of intrathecal drug delivery
The aim of this principally experimental study is to understand from fluid mechanic principles why an insignificant anesthetic dose administered as a short bolus into the cerebrospinal fluid inside the subarachnoid space provides greater pain relief than a larger dose continuously injected over a longer period. The subarachnoid space is modeled as an annular gap of constant or slowly varying cross section into which a catheter is introduced. The cerebrospinal fluid is replaced by water of 37°C which has very similar properties. This fluid in the annular gap is subjected to oscillations of amplitude and frequency (heart frequency) typically found in the subarachnoid space. The anesthetic is replaced by a fluorescent dye injected through the catheter. To study its dispersion, we have developed a 400 Hz laser scanning setup with which we perform quasi-instantaneous, quantitative 3D laser induced fluorescence (LIF) as well as 2D particle image velocimetry (PIV). The experiments are supplemented by an analytical axi-symmetric model as well as an exploratory numerical model to help interpret the results. The study has identified steady streaming (a nonlinear effect associated with the fluid oscillation) and enhanced diffusion (an effect associated with oscillating shear flow) as the principal agents of dye (anesthetic) dispersion. Besides the slowly varying cross section, the catheter tip has been identified as an important cause for steady streaming. In an attempt to identify optimal injection parameters of use for clinicians, a rough parametric model of the primary factors influencing drug spread (fluid oscillation frequency and amplitude, geometry, and injection rate) has been constructed.
Keywords: intrathecal drug delivery ; injection rate ; enhanced diffusion ; steady streaming ; laser induced fluorescence ; particle image velocimetry ; administration intrathécale ; taux d'injection ; diffusion augmentée ; écoulement redressé ; fluorescence induite par laser ; vélocimétrie d'image de particulesThèse École polytechnique fédérale de Lausanne EPFL, n° 4061 (2008)
Programme doctoral Mécanique
Faculté des sciences et techniques de l'ingénieur
Institut de génie mécanique
Laboratoire de mécanique des fluides
Record created on 2008-02-14, modified on 2016-08-08