US3212642A - Artificial kidney - Google Patents

Description

Oct. 19, 1965 J. A. KYLSTRA ARTIFICIAL KIDNEY Filed July 3. 1961 RINSING FLUID BLOOD BLOOD [has QglG- I 27 VAC UUM 28 p AW 7/ RINSING FLUID INVENTOR. JOHANNES ARNOLD KYLSTRA KIDNEY PRESSURE? m IE 5 0T M R R RA AV BUBBLE CATCHER A FIG. 2

United States Patent 3,212,642 ARTIFICIAL KIDNEY Johannes Arnold Kylstrn, Leiden, Netherlands, assignor to The Cleveland Clinic Foundation, (Ileveland, Ohio Filed July 3, 1961, Ser. No. 121,454 4 Claims. (Cl. 210321) This invention pertains to artificial kidneys and more particularly to that class of artificial kidneys in which a kidney is periodically connected to the circulation system of a human patient to remove impurities from the blood of the patient.

In recent years medical practitioners have succeeded in keeping human beings alive for extended periods of time even though those human beings had irreversibly damaged or non-functioning kidneys. This has been accomplished by Weekly hemodialyses with an artificial kidney. Recently other patients have been kept alive with weekly dialysis even though those patients are afflicted with terminal chronic renal failure.

All of these medical successes have been accomplished with artificial kidneys which are now well-known in the art. These kidneys usually conduct the blood of the patient through a conduit system defined in part by a filter membrane. These membranes permit the passage of blood poisons while preventing the passage of blood cells, proteins or the like. A rinse solution is on the outside of the membrane. Circulation of blood and rinse is caused to occur until suflicient poisons have been diffused into the solution to reduce the quantities of poisons in the blood to an appropriate level.

While there have been a number of remarkable successes with prior artificial kidneys there have also been some failures due to inherent deficiencies in these prior artificial kidneys. Additionally, the facility and ability with which these modern techniques can be practiced has been greatly limited by certain inherent drawbacks in previously available artificial kidneys.

Prior art artificial kidneys have had other inherent drawbacks. Among these are the complexity of them and, inherently then, inordinate manufacturing expense. Because of their complexity, these kidneys have required highly trained and skilled personnel for their use, maintenance, and sterilization. Further, with at least some of these kidneys, their complexity created inordinate and inherent deficiencies which can and have resulted in failures while treatments were in progress.

With the present invention a very simple and inexpensive artificial kidney is provided which can be maintained, operated and sterilized by personnel having a very minimum of training. A very highly dependable kidney has been developed which requires no pump for the blood supply, no priming with donor blood prior to use, and 'no specialized and difficult to obtain elements.

These and other advantages are obtained through an assembly which is composed of a plurality of sandwiches. Each sandwich is composed of a stack of flat sheets of appropriate materials which are formed to provide a fluid chamber. The chamber is separated into a blood compartment and a pair of rinsing fluid compartments on either side of the blood compartment. This separation of the chamber into compartments is obtained with a spaced pair of membranes which are pervious to poisons in the blood, allowing the poisons to pass into the rinsing fluid. At the same time the membranes are impervious to the passage of proteinaceous matter, blood cells and other constituents of the blood which should not be lost.

In the preferred arrangement, as is suggested above, each assembly is composed of a plurality of these sand- .wiches. The sandwiches are placed together in a single 3,212,642 Patented Get. 19, 1965 frame with the rinse and the blood compartments of each sandwich parallel connected to the corresponding compartments of the other sandwiches. Usually a pair of frame assemblies will be used with the sandwiches of one frame assembly connected in series with the sandwiches of the other assembly.

Accordingly, one of the principal objects of this invention is to provide a novel and improved artificial kidney which is simple and dependable and which requires no blood pump or blood priming.

Another object of the invention is to provide a kidney sandwich composed substantially entirely of flat sheets of material. This is accomplished by providing a plurality of flat members positioned together in a sandwich which includes a fluid chamber. Flat membranes are positioned between certain of the members to divide the chamber into compartments. Thus, a kidney sandwich is provided which is composed substantially entirely of a series of flat sheets of material.

Another object of the invention is to provide a novel and improved kidney which has a plurality of blood compartments, a rinse chamber compartment on each side of each blood compartment and in which the rinse compartments are parallel connected with one another as are the blood compartments.

Other objects and a fuller understanding of the invention may be had by referring to the following description and claims taken in conjunction with the accompanying drawings in which:

FIGURE 1 is an exploded view of one of the novel and improved kidney sandwiches;

FIGURE 2 is a schematic and diagrammatic view oi one of the artificial kidneys of this invention together with the blood and rinse fluid supply and return conduits and the associated mechanism; and,

FIGURE 3 is a side elevational view of a plurality of the novel kidney assemblies.

Referring to the drawing and to FIGURE 2 in particular, a novel and improved artificial kidney is shown schematically at 10. This kidney 10 is preferably composed of upper and lower kidney assemblies 11, 12, FIGURE 3. The kidney assemblies 11, 12 are each composed of a plurality of kidney sandwiches 13. In the disclosed arrangement of FIGURE 2, the assemblies 11 and 12 are each composed of three such sandwiches. The details of construction of each such sandwich are shown in detail in FIGURE l, and will be described below.

Referring again to FIGURES 2 and 3, a blood supply conduit 15 is connected to the artificial kidney. FIGURE 3 discloses the proper connection with the blood supply conduit 15 to the upper assembly 11 near the top. Blood supplied to the conduit 15 is obtained from a radial artery. The blood pressure of the human patient is used to force the blood into the upper kidney assembly 11. The blood is gravity fed through the assembly 11 to a connecting blood conduit 16 near the base of this assembly.

Here there are two series connected asssemblies 11, 12, the connecting conduit 16 serves as the blood inlet conduit for the lower assembly 12. The blood is gravity fed through the lower assembly 12. The blood comes out a lower blood outlet conduit 17 connected near the base of the lower assembly 12.

The blood outlet conduit 17 conducts the blood to a bubble catcher 18 which separates entrained air from the blood. After the air has been separated the blood is conducted to an arm vein by a suitable blood return conduit 20. The supply and return conduits 15 and 20 will be connected to the artery and vein respectively by the usual cannulae. Thus an extracorporeal blood conduit system is provided which is composed of the conduits 15, 16, 17,

and portions of the assemblies, 11, 12 and the bubble catcher 18.

A rinsing fluid supply reservoir 22 is provided. The rinsing fluid is conducted by a rinse supply conduit 23 from the reservoir 22 to a rinse inlet 24 at the base of the lower kidney assembly 12. The rinse fluid passes up through the lower assembly 12 and thence through a connecting conduit 25. The connecting conduit 25 connects the top of the lower assembly 12 with the base of the upper assembly 11. The rinse fluid is then forced upwardly through the upper assembly 11. After it has passed through the upper assembly 11, the rinse'fluid is returned to the reservoir 22 by a rinse return conduit 27. A vacuum pump 28 is connected in the return conduit 27 and used to cause the rinse fluid to flow through the conduits and the artificial kidney.

A shunt line conduit 29 connects the reservoir 22 to the pump 28 on its suction side. The sub-atmospheric pressure in the rinsing fluid system is adjusted by means of a valve 30 in the shunt line 29.

In FIGURE 1, the details of the construction of each sandwich 13 are shown. Each assembly includes plates 35, 36. Because of their relative positions in the drawings, as opposed to their use positions, these plates 35, 36 will be identified respectively as top and bottom plates. One or more intermediate plates 37 are also provided. The number of intermediate plates 37 is dependent upon the number of sandwiches 13 of each frame assembly 11 or 12. These plates may be made of plexiglass or other suitable material which will not contaminate the blood or rinse fluid. Each intermediate plate serves as a top plate for one contiguous sandwich and a bottom plate for the other. It will be seen that the kidney may be a single sandwich, but again, two or three sandwiches are preferred.

The bottom plate has, inlet and outlet rinse fluid channels 38, 39 formed in its upper face. The top plate has corresponding elongated and parallel inlet and outlet rinse fluid channels 40, 41 formed in its lower surface. Each intermednate plate 37 has similar channels 42, 43, the

distinction being that the channels 42, 43 of the intermediate are through channels to communicate with chambers on either side of the plate.

Each sandwich has a pair of spaced rectangular spacer frames 45, 46. The spacer frame 45 is adjacent the upper plate, whether it be an intermediate plate 37 or top plate 35, while the spacer frame 46 is adjacent the lower plate, whether it be a bottom plate 36 or an intermediate plate 37. In the preferred arrangement these spacer frames are formed of vinyl sheet material of .06 inch in thickness.

The spacer frames 45, 46 have central rectangular passages 47, 48 respectively. These spacer frame passages are each filled by a mat of corrugated filter plastic cloth 49. This filter cloth may be the fabric sold under the trademark Trilok Style TR 3202 by the National Filter Media Corporation, New Haven, Connecticut.

A pair of spaced filter membranes 50, 51 are provided. The filter membranes 50, 51 are positioned adjacent the spacer frames 45, 46 respectively. These membranes are preferably commercial cellophane which has not been boiled or otherwise chemically treated. While cellophane is the accepted known material for these membranes, the important thing is that these membranes must be formed of sheet material having suflicient porosity to pass blood poisons through them. At the same time they must be sufiiciently impervious to prevent the passage of important blood constituents such as blood cells and Proteinous matter. The membranes must be sufliciently inert to avoid contamination of the blood. The membranes must also permit the diffusion of blood impurities into the rinse fluid. This rinse fluid will usually be a solution of water glucose and various salts such as the chlorides of sodium, magnesium, calcium and potassium. Lactic acid is usually added and the pH of the fluid is maintained compatable with that of the blood.

Upper and lower supporting rectangular supporting frames 53, 54 are positioned against the membranes 50, 51 respectively. The supporting frames are preferably the material sold by the E. I. du Pont de Nemours and Co. under the trademark Mylar. This material is a polyester film. It is the glycol ester of terephthalic acid. These supporting frames are each preferably 0.01 inch in thickness and each have rectangular passages 55, 56. The supporting frames 53, 54 are provided to serve both to support the cellophane membranes and to maintain them in appropriate spaced relationship with a central blood frame 58. The blood frame 58 is preferably a vinyl sheet of 0.04 inch thickness. The blood frame has a central rectangular passage 59 and communicating inlet and outlet blood passages 60, 61. l

The rectangular passages 47, 48 of the spacer frames 55, 56 of the supporting frames and 59 of the blood frame are all aligned and in communication to provide an internal fluid chamber. This chamber is separated into a central blood compartment and spaced rinse fluid compartments on either side of the blood compartment by a cellophane membrane 50, 51. The passages and the exchange areas provided by the membranes 50, 51 should .be approximately 0.2 square meter in cross sectional area.

The channels of the plates communicate with contiguous rinse fluid compartments for the supply and return of rinse fluid to and from these compartments. Communication between the channels is obtained by aligned rinse fluid passages in each of the frames and the membranes. As is best seen in FIGURE 1, these rinse fluid passages define conduits designated generally by the numeral 63. These conduits 63 connect the rinse compartments of each frame assembly in parallel with one another. The conduits 63 communicate with the rinse fluid supply and return conduits to place the compartments of the assembly 11 are in series with the compartments of the other assembly 12.

Similarly, the plates, frames and membranes are apertured to provide blood conduits 65 which communicate with the blood frame inlet and outlet passages 60, 61. The blood conduits 65 connect the blood compartments of each frame assembly in parallel with one another. The blood conduits 65 also communicate with the supply and return conduits to place the compartments of the assembly 11 in series with the blood compartments of the assembly 12.

During the manufacture, the various spacers, the membrances and the plates are simply stacked in suitable and aligned relationship and clamped together. Suitable loeating dowels 66 may be provided to assure appropriate alignment of these elements. The clamping is effected by appropriate clamp frames shown generally at 67.

Operation When a patient is to be treated with one of the artificial kidneys of the invention the various elements of the kidney are first stacked to provide the desired number of sandwiches in an assembly. Usually either two or three blood compartments per assembly. The sandwiches are clamped together by the clamp frames 67 and then tested for possible leaks.

This leak testing is accomplished by inflating the blood compartment with air and timing the drop in air pressure after both the inlets and the outlets have been closed off. When more than three minutes are required for the air pressure to diminish from 140 to millimeters of mercury, the unit is blood tight and ready to be sterilized. The sterilization is accomplished with ethylene oxide. The unit is exposed to this ethylene oxide for four hours at F. and 10 pounds per square inch.

In a. typical use, two assemblies, connected in series, are suspended perpendicularly from an intravenous infusion stand. The extracorporeal blood conduit system is flushed with one liter of normal saline and subsequently filled from below with a solution of 50 mg./l. of heparin in saline. The blood portion of the kidney is primed from below to expel air from the system.

' As has been suggested above, it is not necessary to prime the artificial kidney with donor blood. A cannula in an artery is simply connected to the kidney by plastic tubing. The saline in the blood compartment is permitted to drain from the return conduit 20 until the color of the effluent turns red. The return conduit is then connected with a cannula in a vein.

A heparin solution is prepared in advance by adding 500 mg. of heparin to 1 liter of 0.9% saline. At the time of first establishing arterial blood flow into the artificial kidney, 100 ml. of this heparin solution (50 mg. of heparin) is infused at a rapid rate int-o the arterial line by admitting compressed air to the infusion bottle. The heparin infusion rate is then slowed down to a drip and adjusted to maintain the clotting time (one tube) of samples obtained from the return conduit at approximately one hour. At the end of the dialysis, the supply conduit is clamped and blood in the extracorporeal conduit is reinfused into the patient through the blood return conduit 20, either by gravity alone or by saline infusion or air insufllation into the arterial line.

For the long-term dialysis, 300 liters of rinsing solution are maintained at from 5 to 10 C. in a home deepfreeze unit to minimize heparin requirement and inhibit the multiplication of micro-organisms in the solution which is not renewed during the procedure. The blood which is cooled during its passage through the kidney is rewarmed to approximate body temperature in a coil of tubing submerged in a thermostatically controlled water bath before returning to the vein (not shown).

In experimental tests of this artificial kidney using the described technique, no untoward reactions have been observed which could be attributed to the equipment used. On the contrary, patients with previous artificial kidney experience unanimously preferred treatment with this kidney. Most patients fell asleep after the dialysis had begun. This was not accompanied by any appreciable drop in blood pressure. They had quiet nights and enjoyed their meals. Patients who had been maintained by weekly hemodialysis with prior artificial kidneys and who had required antihypertensive drugs on these occasions did not develop any significant elevation in blood pressure when treated with the mechanism of this invention.

In only one out of cases was a pump required to maintain adequate extracorporeal flow due to a high resistance to blood flow in the vein. On all other occasions, flow rates of from 100 to 250 ml./min. were obtained without the use of a blood pump. The site and position of the arterial and venous cannulae as well as the resistance to blood flow in the vein itself (venoconstriction, outside pressure) appears to primarily determine the extracorporeal flow rate. The impedance to blood flow of the unit itself is low. With a pressure head of 80 cm. of blood (60 mm. Hg), a flow of 125 ml./min. was obtained through two series connected triple sandwich assemblies with six blood compartments (1.2 membrane).

The volume of the patients blood in the extracorporeal system depends mainly on the number of blood compartments in the kidney and on the length and diameter of the tubing. It is affected only to a limited extent by the suction applied to the rinsing fluid and by the arterial blood pressure and venous resistance. The blood hold-up volume of two triple sandwich assemblies is no more than 600 ml. This includes the heating coil. Nearly all of this blood may be reinfused into the patient at the end of the dialysis.

In adults, satisfactory weight loss and improvement in the chemical composition of body fluid has been consistently achieved in all instances in which two assemblies with 1.2 m? exchange and filter area were used. It appears likely that one sandwich would suffice in children.

From a technical and economical point of view, this kidney offers advantages. No donor blood is required to prime the apparatus. This eliminates undesirable reactions not infrequently seen in patients who receive multiple and frequent blood transfusions. Since almost all of the extracorporeal blood may be reinfused at the end of the procedure, the total blood loss, on the average, does not necessarily exceed 50 ml. No pump is needed to propel the blood through the system unless excessive venous resistance is present. Management and supervision during the procedure is simple. Emergency situations which may result from mechanical failure are limited to rupture of the membrane and disconnection of the blood tubing and these possibilities are substantially eliminated by the described air testing. This is demonstrated by the fact that rupture of the membrane has not occurred during any of the test dialyses which have been conducted. Should either of these emergencies arise, mere clamping of the arterial and venous cannulae will suflice to prevent exsanguination. Clotting of the blood in the kidney may diminish or arrest extracorporeal flow but does not give rise to other complications when no blood pump is used.

Summary While the invention has been described with a great deal of detail it is believed that it essentially comprises a frame assembly having a plurality of flat elements stacked together in at least one sandwich. Each sand- Which includes a chamber separated into blood and rinse compartments by sheet-like membranes.

Although the invention has been described in its preferred form with a certain degree of particularity, it is understood that the present disclosure of the preferred form has been made only by way of example and that numerous changes in the details of construction and the combination and arrangement of parts may be resorted to without departing from the spirit and the scope of the invention as hereinafter claimed.

What is claimed is:

1. In an artificial kidney including a supply of rinse fluid, conduits to conduct rinse fluid to and from the kidney, other conduits to conduct human blood to and from the kidney and a bubble catcher in the return conduit to separate air from the blood, the combination of, a plurality of blood purifying sandwiches each connected to both the blood and rinse fluid conduits, each sandwich comprising, a pair of spaced plates, a pair of spacer frames interposed between the plates, each of the spacer frames being adjacent one of the plates, a pair of membrane sheets interposed between the spacer frames with each sheet adjacent one of the spacer frames, a pair of supporting frame members interposed between the membrane sheets and each adjacent one of the sheets, a blood frame interposed between the supporting frames, each of said frames having a through central passage surrounded by the associated frame, said central passages being aligned and in communication with one another to define a purifying chamber, said membranes separating said chamber into first and second rinse fluid compartments and a blood compartment therebetween, a mat of filter cloth in each filter section, said plates each having a spaced pair of elongated fluid channels each communicating with a contiguous rinse fluid compartment, said frames and sheets having apertures therein aligned with one another to provide a rinse fluid conduit connecting one of the channels of one plate with one of the channels of the other plate, said first plate having an inlet aperture therein communicating with the other of the channels of the first plate, said second plate having an outlet aperture therein communicating with the other of the channels in the second plate, said inlet and outlet apertures being connected to said rinse fluid conduits, said frames and plates having other apertures therein aligned and in communication to define blood inlet and outlet passages communicating with said blood compartment, and said plate, said mats, said frames and said membranes all being sufficiently inert chemically to be free of chemical reaction with blood and rinse fluid.

2. The device of claim 1 wherein said membrane sheets are cellophane.

3. An artificial kidney comprising:

(a) a pair of spaced plates;

(b) a pair of spacer frames interposed between the plates;

(c) a pair of membrane sheets interposed between the spacer frames;

(d) a blood frame interposed between the membrane sheets;

(e) each of said frames defining a through central passage, said central passages being aligned and in communication with one another to define a puritying chamber;

(f) said membranes each being clamped between the blood frame and a diflerent one of the spacer frames such that portions of the membranes separate said chamber into first and second rinse fluid compartments and a blood compartment therebetween;

g) said plates and said frames having apertures therein aligned and in communication to define rinse fluid and blood inlet and outlet passages communicating with said rinse fluid and blood compartments respectively;

(h) said plate, said frames and said membranes all being sufliciently inert chemically to be free of chemical reaction in the presence of blood and rinse fluid;

(i) clamp means fixing the plates, the spacers and the membranes together; and,

(j) a pair of woven plastic mats each substantially filling a different one of said rinse fluid compartmentsand supporting said membranes when the kidney is in use.

4. In an artificial kidney, the improvement which comprises:

(a) members including a central member defining an internal fluid chamber;

(b) a pair of filter membrane sheets extending across the chamber with the central member between the membranes to define a blood compartment;

(0) said members including enclosure means on the sides of the membranes opposite said central member, said enclosure means cooperating with said membranes to define a pair of rinse compartments,

(d) clamp means clamping the member together and maintaining the sheets extended; and

(e) a pair of woven plastic filter mats each substantially filling a different one of the rinse compartments to reinforce the membranes when the kidney is in use while permitting free flow of fluid in said rinse compartments and intimate contact of rinse fluid with substantially all of the area of the mem-' branes communicating with said rinse compartments and intimate contact by blood over the entire area of said membranes exposed to said blood compartment.

References Cited by the Examiner UNITED STATES PATENTS 2,568,990 9/51 Daniel.

2,686,154 8/54 MacNeill 210-321 3,034,505 5/62 Sobol 128-214 3,060,934 10/62 Claff et al 210-321 X 3,072,259 1/63 Isreeli 210-321 X OTHER REFERENCES Anthonisin et al.: Clinical Experience with the Skeggs- Leonards Type of Artificial Kidney, Lancet, December 22, 1956, pgs. 1277-1278.

Hollander et al.: A New Type of Artificial Kidney, Journal of Urology, May 1953, vol. 69, #5, pgs. 605-613.

Clowes et al.: An Artifical Lung Dependent upon Diffusion of Oxygen and Carbon Dioxide Through Plastic Membranes, Journal of Thoracic Surgery, November 1956, vol. 32, #5, pgs. 630-637.

REUBEN FRIEDMAN, Primary Examiner.

HARRY B. THORNTON, RICHARD J. HOFFMAN,

Examiners.

Claims (1)

1. IN AN ARTIFICAL KIDNEY INCLUDING A SUPPLY OF RINSE FLUID, CONDUITS TO CONDUCT RINSE FLUID TO AND FROM THE KIDNEY, OTHER CONDUITS TO CONDUCT HUMAN BLOOD TO AND FROM THE KIDNEY AND A BUBBLE CATCHER IN THE RETURN CONDUIT TO SEPARATE AIR FROM THE BLOOD, THE COMBINATION OF, A PLURALITY OF BLOOD PURIFYING SANDWICHES EACH CONNECTED TO BOTH THE BLOOD AND RINSE FLUID CONDUITS, EACH SANDWICH COMPRISING, A PAIR OF SPACED PLATES, A PAIR OF SPACER FRAMES INTERPOSED BETWEEN THE PLATES, EACH OF THE SPACER FRAMES BEING ADJACENT ONE OF THE PLATES, A PAIR OF MEMBRANE SHEETS INTERPOSED BETWEEN THE SPACER FRAMES WITH EACH SHEET ADJACENT ONE OF THE SPACER FRAMES, A PAIR OF SUPPORTING FRAME MEMBERS INTERPOSED BETWEEN THE MEMBRANE SHEETS AND EACH ADJACENT ONE OF THE SHEETS, A BLOOD FRAME INTERPOSED BETWEEN THE SUPPORTING FRAMES, EACH OF SAID FRAMES HAVING A THROUGH CENTRAL PASSAGE SURROUNDED BY THE ASSOCIATED FRAME, SAID CENTRAL PASSAGES BEING ALIGNED AND IN COMMUNICATION WITH ONE ANOTHER TO DEFINE A PURIFYING CHAMBR, SAID MEMBRANES SEPARATING SAID CHAMBER INTO FIRST AND SECOND RINSE FLUID COMPARTMENTS AND A BLOOD COMPARTMENT THEREBETWEEN, A MAT OF FILTER CLOTH IN EACH FILTER SECTION, SAID PLATES EACH HAVING A SPACED PAIR OF ELONGATED FLUID CHANNELS EACH COMMUNICATING WITH A CONTIGUOUS RINSE FLUID COMPARTMENT, SAID FRAMES AND SHEETS HAVING APERTURES THEREIN ALIGNED WITH ONE ANOTHER TO PROVIDE A RINSE FLUID CONDUIT CONNECTING ONE OF THE CHANNELS OF ONE PLATE WITH ONE OF THE CHANNELS OF THE OTHER PLATE, SAID FIRST PLATE HAVING AN INLET APERTURE THEREIN COMMUNICAING WITH THE OTHER OF THE CHANNELS OF THE FIRST PLATE, SAID SECOND PLATE HAVING AN OUTLET APERTURE THEREIN COMMUNICATING WITH THE OTHER OF THE CHANNELS OF THE SECOND PLATE, SAID INLET AND OUTLET APERTURES BEING CONNECTED TO SAID RINSE FLUID CONDUITS, SAID FRAMES AND PLATES HAVING OTHER APERTURES THEREIN ALIGNED AND IN COMMUNICATION TO DEFINE BLOOD INLET AND OUTLET PASSAGES COMMUNICATING WITH SAID BLOOD COMPARTMENT, AND SAID PLATE, SAID MATS, SAID FRAMES AND SAID MEMBRANES ALL BEING SUFFICIENTLY INERT CHEMICALLY TO BE FREE OF CHEMICAL REACTION WITH BLOOD AND RINSE FLUID.

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