Biomedical Engineering Reference
In-Depth Information
At present, the clinical approach to acute and acute-on-chronic liver failure is mainly
based on blood detoxification as a temporary solution aimed at keeping patients alive in
wait of a recovery of liver functionality or an organ transplantation. Blood detoxification is
performed by means of extracorporeal liver support devices (LSDs), whose primary aim is
to remove selectively the noxious substances, while avoiding the depletion of biologically
valuable macromolecules, like proteins, hormones and growth factors.
This task is successfully performed in the treatment of renal failure with hemodialysis,
for the removal of small, water-soluble toxins such as urea and creatinine. However, toxins
not cleared by the failing liver include also molecules that are tightly bound to plasma
proteins such as albumin, and more complex processes are required for blood detoxification
in this case.
The first detoxification process specifically designed for the removal of albumin-bound
toxins is Albumin Dialysis (AD, Stange et al. 1993). Basically, this process consists in
blood dialysis across a special albumin impregnated membrane against a concentrated albu-
min solution (albumin dialysate). The particular structure of the membrane and the presence
of a binder in the dialysate allow for albumin-bound toxin transfer across the membrane,
while the cut-off of the membrane is chosen so as to avoid transfer of albumin and higher
molecular weight substances.
AD can be either applied without recirculation of the albumin dialysate, as in Single
Pass Albumin Dialysis (SPAD, Sauer et al., 2004), or with regeneration and recirculation of
the dialysate, as in the MARS (Molecular Adsorbents Recirculating System, Gambro, Lund,
Sweden). This latter device, that is one of the best-known LSDs used in clinical practice,
implements AD with on-line regeneration of the albumin dialysate by conventional dialysis
and adsorption on activated carbon and anionic resin (see Fig. 1.).
Another detoxification process designed for albumin-bound toxin removal is Fraction-
ated Plasma Separation and Adsorption (FPSA, Falkenhagen et al., 1999). The clinically
used LSD that implements this process is the Prometheus (Rifai et al., 2005, Evenopoel et
al., 2005), which is schematically represented in Fig. 1.. In this device, plasma is filtered
from blood along with albumin and smaller molecules, circulated in closed loop through
one anionic resin and one non-ionic resin column in series, and then sent back into the
patient blood circuit.
Other processes have been proposed (for a review see Stegmayr et al. 2005 and Rozga
et al. 2006), anyway, under a general point of view, it can be affirmed that all of them are
based on some combination of dialysis and adsorption unit operations.
Analysis and comparison of the performance of the different LSDs is currently based
mainly on clinical criteria (Mitzner et al. 2006 and Evenopoel et al. 2006). It is clear that
in-vivo clinical tests of LSDs are essential and can certainly not be substituted with in-vitro
experiments and theoretical considerations only; nevertheless, the patient-device system is
extremely complex and it is hard to gain insight into the detoxification process by the mere
analysis of clinical data. As a consequence, at present it is difficult to define rationally the
advantages and drawbacks of different device configurations.
In this chapter, an engineering approach is applied to the analysis of LSDs. Starting
from a description of the physico-chemical phenomena that characterize each unit opera-
tion of the detoxification process, mathematical models of dialysis and adsorption units are
developed and combined into a LSD model. The analysis refers to a MARS-type LSD and is
