Hemodialysis

Researchers at Oregon State University have demonstrated the advantages of microchannel architecture in improving the hemodialysis process. Using microchannel architectare, they were able to show 70-80% reductions in the necessary transfer area relative to commercial hollow fiber systems for the clearance of creatinin (Fig. 7.23) and urea (Fig. 7.24) from a simulated blood stream [285]. The microchannel advantage, as has been seen in other applications, comes in the form of well-defined and narrow channels that facilitate rapid mass transfer into and out of the fluid media. This approach is expected to change the current paradigm in hemodialysis from clinical treatment to at-home use, and may allow for the creation of a wearable hemodialyzer [286]. 

Notninal velocity of the Blood S jbstit Jte in p-channels tniii/s] 

Osmosis refers to the movement of solvent throngh a membrane from the side where the solute concentration is lower to the side where the solute concentration is higher. Hemodialysis involves a more porous membrane, through which both solvent (water) and small solute partieles can pass. 

In this chapter, the use of membranes in medical devices is reviewed briefly. In terms of total membrane area produced, medical applications are at least equivalent to all industrial membrane applications combined. In terms of dollar value of the products, the market is far larger. In spite of this, little communication between these two membrane areas has occurred over the years. Medical and industrial membrane developers each have their own journals, societies and meetings, and rarely look over the fence to see what the other is doing. This book cannot reverse 50 years of history, but every industrial membrane technologist should at least be aware of the main features of medical applications of membranes. Therefore, in this chapter, the three most important applications—hemodialysis (the artificial kidney), blood oxygenation (the artificial lung) and controlled release pharmaceuticals—are briefly reviewed. 

The kidney is a key component of the body s waste disposal and acid-base regulation mechanisms. Each year approximately one person in ten thousand suffers irreversible kidney failure. Before 1960, this condition was universally fatal [1] but now a number of treatment methods can maintain these patients. Of these, hemodialysis is by far the most important, and approximately 800 000 patients worldwide benefit from the process. Each patient is dialyzed approximately three times per week with a dialyzer containing about 1 m2 of membrane area. Economies of scale allow these devices to be produced for about US 15 each the devices are generally discarded after one or two uses. As a result the market for dialyzers alone is about US 1.3 billion [2,3], 

Membrane Technology and Applications R. W. Baker 2004 John Wiley Sons, Ltd ISBN 0-470-85445-6 

Kolf s early devices were used for patients who had suffered acute kidney failure as a result of trauma or poisoning and needed dialysis only a few times. Such emergency treatment was the main application of hemodialysis until the early 1960s, because patients suffering from chronic kidney disease require dialysis two to three times per week for several years, which was not practical with these early devices. However, application of hemodialysis to this class of patient was made possible by improvements in the dialyzer design in the 1960s. The development of a plastic shunt that could be permanently fitted to the patient to allow easy access to their blood supply was also important. This shunt, developed by Scribner et al. [6], allowed dialysis without the need for surgery to connect the patient s blood vessels to the dialysis machine for each treatment. 

Hollow fiber dialyzers typically contain 1 -2 m2 of membrane in the form of fibers 0.1-0.2 mm in diameter. A typical dialyzer module may contain several thousand fibers housed in a 2-in.-diameter tube, 1-2 ft long. Approximately 

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Fig. 1. A, hoUow-fiber spool B, hoUow-fiber cartridge employed ia hemodialysis C, cartridge identical to item B demonstrating high packing density D, hoUow-fiber assembly employed for tissue ceU growth E, hoUow-fiber bundle potted at its ends to be inserted into a cartridge or employed ia a situation...

Fiber dimensions have been studied for hemodialysis. When blood is circulated through the fiber lumen (m vivo), a significant reduction in apparent blood viscosity may occur if the flow-path diameter is below 100 p.m (11). Therefore, current dialy2ers use fibers with internal diameters of 180—250 p.m to obtain the maximum surface area within a safe range (see Dialysis). The relationship between the fiber cross section and the blood cells is shown in Figure 5. In many industrial appUcations, where the bore fluid is dialy2ed under elevated pressure (>200 kPa or 2 atm), fibers may burst at points of imperfection. Failure of this nature is especially likely for asymmetric fibers that display a large number of macro voids within the walls. 

Fig. 14. Mass transfer across hemodialysis and hemofiltration hoUow-fiber membranes.

Hollow Fiber with Sorbent Walls. A cellulose sorbent and dialy2ing membrane hoUow fiber was reported in 1977 by Enka Glan2stoff AG (41). This hoUow fiber, with an inside diameter of about 300 p.m, has a double-layer waU. The inner waU consists of Cuprophan ceUulose and is very thin, approximately 8 p.m. The outer waU, which is ca 40-p.m thick, consists mainly of sorbent substance bonded by ceUulose. The advantage of such a fiber is that it combines the principles of hemodialysis with those of hemoperfusion. Two such fibers have been made one with activated carbon in the fiber waU, and one with aluminum oxide, which is a phosphate binder (also see Dialysis). 

M. A. Newberry, Textbook of Hemodialysis for Patient Care Personnel, CC Thomas, Springfield, lU., 1989. 

One unique appHcation area for PSF is in membrane separation uses. Asymmetric PSF membranes are used in ultrafiltration, reverse osmosis, and ambulatory hemodialysis (artificial kidney) units. Gas-separation membrane technology was developed in the 1970s based on a polysulfone coating appHed to a hoUow-fiber support. The PRISM (Monsanto) gas-separation system based on this concept has been a significant breakthrough in gas-separation... 

Grafts are also frequently employed in the upper part of the body to reconstmct damaged portions of the aorta and carotid arteries. In addition, grafts are used to access the vascular system, such as in hemodialysis to avoid damage of vessels from repeated needle punctures. Most grafts are synthetic and made from materials such as Dacron or Teflon. Less than 5% of grafts utilized are made from biological materials. 

Polyurethanes as Biomaterials. Much of the progress in cardiovascular devices can be attributed to advances in preparing biostable polyurethanes. Biostable polycarbonate-based polyurethane materials such as Corethane (9) and ChronoFlex (10) offer far-reaching capabiUties to cardiovascular products. These and other polyurethane materials offer significant advantages for important long-term products, such as implantable ports, hemodialysis, and peripheral catheters pacemaker interfaces and leads and vascular grafts. 

A variety of therapies for thallium poisoning have been suggested by neutralising thallium in the intestinal tract, hastening excretion after resorption, or decreasing absorption. Berlin-Blue (fertihexacyanate) and sodium iodide in a 1 wt % solution have been recommended. Forced diuresis hemoperfusion and hemodialysis in combination results in the elimination of up to 40% of the resorbed thaHous sulfate (39). 

Engineering Aspects of Hemodialysis. Engineering interest in hemodialysis is concentrated on the optimization of the hemodialysis membrane (4,41), the dependency of solute removal on membrane and device characteristics (14,15), and quantitation of hemodialysis therapy through urea pharmacokinetics (42—44). 

Fig. 6. Solute transport in hemodialysis. Clearance vs solute mol wt for dialy2ers prepared from the two different membranes illustrated in Figure 5. Numbers next to points represent in min /cm calculated from equations 10 and 5. Data is in vitro at 37°C with saline as the perfusion fluid. Lumen flow, dialysate flow, and transmembrane pressure were 200 ml,/min, 500 mL/min, and 13.3 kPa (100 mm Hg) area = 1.6. Inulin clearance of the SPAN...

Urea Pharmacokinetics. Pharmacokinetics summarizes the relationships between solute generation, solute removal, and concentration in a patient s blood stream. In the context of hemodialysis, this analysis is most readily appHed to urea, which has, as a consequence, become a surrogate for other uremic toxins in the quantitation of therapy and in attempts to describe its adequacy. In the simplest case, a patient is assumed to have no residual renal function. Urea is generated from the breakdown of dietary protein, accumulates in a single pool equivalent to the patient s fluid volume, and is removed uniformly from that pool during hemodialysis. A mass balance around the patient yields the following differential equation ... 

A 3.5 h treatment of a 70 kg patient (V = 40.6 liters) with a urea clearance of 200 ml,/min should result in a 64% reduction in urea concentration or a value of 0.36 for the ratio d (f this parameter almost always falls between 0.30 and 0.45. The increase in urea concentration between hemodialysis treatments is obtained from equation 13, again assuming a constant V, where (f is the urea concentration in the patient s blood at the end of the hemodialysis, and d the concentration at time t during the intradialytic interval. 

Maintenance hemodialysis has grown and expanded beyond the expectations of even the most enthusiastic of its eadiest proponents. Figure 7 is a plot of the overall estimated dialysis population by year siace 1970. The population at the end of 1992 exceeded 475,000 another 500,000 patients or so have received therapy at one time but have siace died or had transplants. Maintenance dialysis is now available to some extent ia all but the poorest nations ia economically advanced countries, excepting the United Kingdom, it is rendered as a virtual entitlement. The current worldwide mean cost of a single dialysis patient is about 30,000 per year (47) the aggregate economic magnitude of the medical appHcation of hemodialysis thus approaches 15 biUion. 

Fig. 7. Estimate of the total number of patients receiving maintenance dialysis over the past 20 years. Totals include both hemodialysis and peritoneal dialysis, but exclude transplant recipients. The fraction of patients receiving peritoneal dialysis has grown steadily from 0% in 1978 to about 12% in 1992. These data were combined from various regional registries and industry sources demographic estimates of this iLk are accurate to within 5% (46). D,...

Hemodialysis with microencapsulated urease and an ammonia ion adsorbent, zirconium phosphate [13772-29-7], has been used (247) to delay the onset of dialysis therapy in patients retaining some renal function, and to reduce the time between dialysis treatment. 

Dialysis and Hemodialysis Historically, dialvsis has found some industrial use. Today, much of that is supplanted by iiltrafiltration, Donan dialysis is treated briefly under electrodialysis. Hemodialysis is a huge application for membranes, and it dominates the membrane field in area produced and in rnonetaiv aliie. This medical application is omitted here. 

Block GA, Martin KJ, de Francisco AL et al (2004) Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. N Engl J Med 350 1516-1525... 

The effect of hemodialysis can be derived from the removed fraction (FR) that is the relative amount eliminated from the body during the time (/HD) of one dialysis session. This fraction can be derived from the half-life on dialysis (Tl/2on) or from the area under the curve (AUC) on and off dialysis. 

After dialysis, often a rebound is seen in concentrations since elimination from plasma is faster than drug flux from tissue to plasma (Crebound — Ctissue - C). The concentration in plasma follows a bi-exponential kinetics during hemodialysis whereas the concentration in tissue follows mono-exponential kinetics. 

Vitamin C requirements are increased during pregnancy and lactation, in patients undergoing hemodialysis and in smokers. Seniors often have suboptimal intakes. 

The nurse monitors the patient for signs and symptoms of acute salicylate toxicity or salicylism (see Display 17-1). Initial treatment includes induction of emesis or gastric lavage to remove any unabsorbed drug from the stomach. Activated charcoal diminishes salicylate absorption if given within 2 hours of ingestion. Further therapy is supportive (reduce hyperthermia and treat severe convulsions with diazepam). Hemodialysis is effective in removing Hie salicylate but is used only in patients with severe salicylism. 

Treatment of barbiturate toxicity is mainly supportive (ie, maintaining a patent airway, oxygen administration, monitoring vital signs and fluid balance). The patient may require treatment for shock, respiratory assistance, administration of activated charcoal, and in severe cases of toxicity, hemodialysis. 

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