Artificial Organs

Artificial Organs: Thoughts dk Progress

Vol. 4, No. 4

It is the goal of this section to publish material which provides information regarding specific issues, aspects of artificial organs’ application, approach, philosophy, suggestions and/or thoughts for the future.

Mini-Hemoperfusion: A New Technique to Evaluate Adsorbents in Humans

Jerry L. Rosenbaum, Mark S. Kramer, Rasib M. Raja, Michael J . Krug, and Crispin G. Bolisay, f rom the Kraftsow Renal Department and the Womens League for Medical Research Laboratories, Albert Einstein Medical Center, York and Tabor Roads, Phi- ladelphia, Pennsylvania 19141, U.S.A.

INTRODUCTION As new hemoperfusion systems are developed, there will be a need to quickly and easily evaluate new adsorbents and reactants in human subjects in order to obtain solute clearance and blood compatibility data.”* Many sorbent properties can be evaluated by constructing a low-flow, low-volume, “mini-column” containing a small quantity of a d ~ o r b e n t . ~ If small enough, the column should have no appreciable sys- temic effect on the patient with respect to i ts adsorp- tion properties or toxicity; however, i t should allow direct recording of clearance and blood compatibility properties. The purpose of this report is to describe such a M-HP device (used ex vivo) as a shunt off of the hernodialysis inflow line i n patients with end- stage renal disease in order to compare three types of commercially available adsorbents.

APPLICATION OF MINI-COLUMN The mini-column consisted of a segment of polyvi- nylchloride tubing packed with 5 gm (wet weight) of test adsorbent (Fig. 1). The adsorbents included uncoated Amberlite XAD-4 resin used in the Amber- sorb XR-004 column (Extracorporeal Medical Spe- cialities, Inc., King of Prussia, Pennsylvania, U.S.A.); activated coconut-based carbon thickly coated (3 to 5 pm) with acrylic hydrogel, used in the Hemocol column (Warner-Chilcott, Morris Plains, New Jersey, U.S.A.); and petroleum-based carbon thinly coated (0.3 to 0.5 pm) with cellulose nitrate, used in the Hemosorba column (Asahi Medical Co., Ltd., Tokyo,

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Japan) . A nylon #150 mesh blood filter was inserted at each end of the adsorbent chamber. The inflow blood line to the mini-column was connected through the rubber cushion on the inflow blood line to the hernodialysis cannister with a # 16 I)ie seret (Deseret Pharmaceutical Co., Inc., Sandy, IJtah, U.S.A.) needle. At the inflow line to the mini-column, there was a small Extracorporeal blood pump (model #P2100), and inlet ports for a heparin infusion syr- inge and a n aneroid pressure manometer. The out- flow line of the mini-circuit was connected to a more distal cushion on the dialysis inflow Mood line by a #16 Deseret needle. The mini-circL.it contained a blood filter consisting of a wad of pyrogen-free dacron wool inserted into the proximal charr,ber of a Milli- pore micro-syringe 25 mm filter-holder (Millipore Corp., Bedford, Massachusetts, U.S.A.) without the filter paper.

Before connecting the M-HP to the hemodialysis system, i t was sterilized with ethylene oxide and aer- ated for a t least 48 hours. Then it was irrigated at a flow rate of 10 ml/min with 100 ml of isotonic saline

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containing 500 units of aqueous heparin, and primed. The filling volume consisted of 12 ml in the column and 13 ml in the tubing. Each patient received aque- ous heparin as required for the hemodialysis. The blood flow rate through the M-HP system was main- tained at 5 ml/min (1 ml/min/gm of adsorbent), and additional heparin was continuously infused at 100 units per hour a t a concentration of 40 uni tdm1 of saline. The column inflow blood sample was collected by aspirating from the dialysis line before the column; the outflow sample was obtained from the outflow line of the mini-circuit by disconnecting the tubing between the column and the distal Deseret needle and directly collecting the blood without interruption of the perfusion blood pump. By noting the rate of blood flow during the collection period, the blood flow rate through the mini-column could be measured directly with each blood sample.

Ten patients with end-stage renal disease had a M-HP of up to three hours with each of the three test adsorbents during routine hemodialysis (Group I, Ambersorb XR-004; Group 11, Hemocol; Group 111, Hemosorba). Platelet counts were determined with a Neubauer counting chamber. Calculations of arith- metic means and standard deviations were per- formed and comparisons ’made according to the appropriate Student’s t-test for paired or unpaired data.

M-HP diid not cause any noticeable side effects. The per cent [decrease in the blood platelet count across the mini-column a t 5,30,60, 120, and 180 minutes of hemoperfusion was 40 k 17,26 k 17,22 i 21,18 i 19, and 15 t 26(Rl for Group I; 33 2 20, 29 t 23, 17 i: 16, 12 i: 10, and 13 ? 13% for Group 11; and 27 k 14, 25 2 16, 26 ? 18, 11 i 10, and 8 i 3% for Group 111. There was a statistically significant (P<O.02) decrease in the absolute mean platelet count across the column within all three groups, but the difference in the per cent decrease was small and not statistically signifi- cant (P>O.O5) between the groups. For Groups 1, I1 and 111, the pre-perfusion mean values for plasma creatinine concentration were 12.7 k 2.9, 13.1 f 2.7, and 12.8 i: 2.3 mg/dl; the mean plasma uric acid con- centrations were 9.2 t 1.2, 8.3 k 0.5, and 9.1 k 1.3 mg/dl; the mean plasma urea nitrogen concentra- tions were 79 2 18 mg/dl, 81 k 18 mg/dl, and 79 f 16 mg/dl, respectively. Plasma clearances of creatinine and uric acid were much higher for Group 111 as compared to Group I1 (P<0.001) throughout the three hours of hemi) perfusion (Figs. 2 & 3). Since the groups were similar in regard to the extent of pre-dialysis azotemia, the differences in the solute clearances closely reflect the differences in the attraction of the respective adsorbents for creatinine and uric acid.

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Artificial Organs Vol. 4, No. 4

needle punctures utilizing antecubital or forearm veins. In addition, it can be used clinically for in fan ts , experimentally with small laboratory animals and for in vitro studies. Although a flow rate of 1 ml/min/gm of adsorbent is commonly used for full-scale clinical hemoperfusion devices in the treatment of acute drug overdose, hepatic failure and renal failure, the M-HP system might not predict all blood compatibility problems in a full-scale cartridge due to differences in geometric configuration affecting l inear flow velocity a n d possibly complement activation.

The M-HP technique should prove of consider- able value in providing a safe, simple, and direct

method of testing blood compatibility and solute clearance for any new adsorbent or reactant prior to full-scale hemoperfusion in humans.

References 1. ROSENBAUM, J.L. Poisonings. Sorbents a n d Their Clinical

Applications. C. Giordano, ed., Academic: Press, Inc., New York, p. 451, 1980.

2. CHANG, T.M.S. Hemoperfusion alone and i n series with ultra- filtration or dialysis for uremia, poisoning and liver failure. Kidney Int, 10:S305, 1976.

3. ROSENBAUM, J.L., MCALACK, R.F., KRAMER, M.S., RAJA, R.M., FALK, B., LEVINE, J., HENRIQUEZ, M. The effect of Amberlite XE-336 resin hemoperfusion and hemodialysis on lymphocyte function in uremic blood (abstrsct). VII Int Congr Nephrol, S-1, 1978.

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