Page 102 - Biomedical Engineering and Design Handbook Volume 2, Applications

OVERVIEW OF CARDIOVASCULAR DEVICES 81

The indications to initiate hemodialysis for ESRD are variable but involve clinical and sympto-
matic manifestations related to uremia, a buildup of metabolic toxins in the blood. Indications requiring
immediate initiation of therapy include encephalopathy or a change in mental status, disturbances in
either the sensory or motor pathways, effusions in the pericardial space or pleura due to uremic
irritation, uncontrollable metabolic derangements such as high serum potassium and low pH, and
excessive water retention (Denker et al,, 2000). Because of evidence suggesting improved outcomes
in patients receiving early dialysis intervention, patient symptoms resulting in a reduced quality of
life (fatigue, cognitive changes, itching, and malnutrition) can be considered as indications for the
initiation of dialysis (Hakim and Lazarus, 1995).
Indications for renal-replacement therapy in the acute setting and for other disease processes are
different from those for ESRD. A common mode of ESRD therapy in the outpatient setting is inter-
mittent hemodialysis (IHD) where a patient receives intense treatment over the course of a few hours
several times a week. Acute renal failure in the inpatient setting is often treated with continuous
renal-replacement therapy (CRRT), which is applied for the entire duration of the patient’s clinical
need and relies upon hemofiltration to a higher degree than IHD (Meyer, 2000). Other nonrenal indi-
cations for CRRT are based on the theoretical removal of inflammatory mediators or toxins and elim-
ination of excess fluid (Schetz, 1999). These illnesses include sepsis and systemic inflammatory
response syndrome, acute respiratory distress syndrome, congestive heart failure with volume over-
load, tumor lysis syndrome, crush injury, and genetic metabolic disturbances (Schetz, 1999).

3.6.3 Device Design
Three physical processes determine the removal rate for uremic toxins through membrane-based
devices. Convection results in toxin removal through a semipermeable membrane that separates blood
from dialysate and can be used to remove excess fluid. A pressure gradient across the membrane is
responsible for the solvent flow, and toxins are removed as a function of their concentration in solu-
tion, the ultrafiltration rate or rate of fluid removal, and the seiving coefficient of the particular toxin
across the membrane barrier. Membranes for convection-based therapies exclude molecules larger
than their pore size but permit improved removal of the middle molecules (500 to 5000 Daltons)
implicated in uremia (Meyer, 2000). Depending on the amount of fluid removed, replacement elec-
trolyte solution may be required to maintain adequate hemodynamic volume. Diffusion-based solute
removal primarily affects smaller molecules with high diffusion coefficients and possessing a favor-
able concentration gradient from the blood to the dialysate. Adsorption is the third and least charac-
terized method of solute removal in renal-replacement therapies (Klinkmann and Vienken, 1995).
Controlled by electrostatic and van der Waals forces between solute and membrane, adsorption-
based removal can be beneficial or harmful, depending on the compound involved, such as removal
of proinflammatory cytokines versus a needed anticoagulant (Klinkmann and Vienken, 1995).
Convection and diffusion remain the dominant physical processes by which membranes and devices
are designed.
Although hemodialysis and hemofiltration are often considered separate therapies, some clinical
treatments rely on a combination of the two and therefore can be classified as hemodiafiltration pro-
cedures. Treatment techniques can be further stratified as to whether they are intermittent or contin-
uous in nature, and whether the vessels accessed are both venous, or arterial and venous. Due to a
lack of definitive prospective randomized trials (Bagshaw et al., 2008), the relative advantage of con-
tinuous versus intermittent treatment is unknown, although continuous administration is felt to be
more “gentle” in some circles, allowing greater time for toxin equilibration and removal (Meyer,
2000) with a possible reduction in blood pressure fluctuation (Bagshaw et al., 2008).

Unit and Membrane Design. Hemodialysis units have undergone a variety of changes since the first
practical design, a rotating drum dialyzer, was introduced in the 1940s (Kolff et al., 1944). As
reviewed by Clark, subsequent unit designs have progressed through coil and parallel flow dialyzers
to the current dominant design of the hollow fiber dialyzer, which was introduced to address perfor-
mance and use limitations inherent in the earlier devices (Clark, 2000). Subsequent to the introduc-
tion of the hollow fiber dialyzer, much of the improvement and development in artificial kidney