Abstract:
An apparatus and method for use in blood dialysis. The apparatus includes: two dialyzers each containing a semipermeable membrane that divides the dialyzer into a blood compartment and a dialysate compartment; a blood compartment connecting line connecting the blood compartments of the dialyzers together in series; blood connecting lines for connecting the blood compartments to the vascular system of a patient; a dialysate compartment connecting unit connecting the dialysate compartments of the dialyzers together in series; and dialysate connecting lines for connecting the dialysate compartments to a dialysis machine. The dialysate compartment connecting unit includes an adjustable flow varying device for controllably setting the rate of the flow of dialysate through the connecting unit.

Description:
BACKGROUND OF THE INVENTION 
     The present invention relates to hemodialysis for removing blood-borne uremic toxins and by-products of metabolism from the blood of patients suffering from renal failure. 
     This procedure is performed in dialysis apparatus generally composed of one or more dialyzers in which a blood compartment is separated from a dialysate compartment by a filter structure and a dialysis machine that controls the rate of flow and composition of the dialysate and monitors the dialysis procedure. 
     Apparatus of this type is available in a variety of forms. For example, the apparatus may be composed of two dialyzers whose respective compartments are connected in parallel or series. Each such form of construction has advantages and disadvantages. All known arrangements have certain drawbacks that adversely affect the quality and/or speed of a complete dialysis procedure. 
     A typical parallel arrangement is disclosed in U.S. Pat. No. 6,117,100. 
     Double high flux (DHF) dialysis is a known technique that uses two high flux dialyzers in series and a volumetric controlled dialysis machine. The dialysate flow path is altered in order to provide pressure differentials across each dialyzer, causing the first dialyzer to act as an ultrafilter while the second dialyzer performs infusion of substitution fluid by backfiltration. This treatment can advantageously be performed in newer machines that offer a sufficient calibration of the transmembrane pressure (TMP) gauge and arterial pressure gauge, a high blood pump speed, two dialysate filters to filter the dialysate fluid prior to entering the dialyzer and a high pressure of the incoming water. 
     DHF has also been referred to as high flux hemodiafiltration. This is because this treatment combines the enhanced convective removal associated with ultrafiltration with the diffusive removal associated with counter current dialysate. The two dialyzers, in series, double the effective surface area. For example, the dialysate flow may be set to 800 ml/min, with approximately 150 ml/min of this used for backfiltration, yielding a useful dialysate flow of 650 ml/min through the first dialyzer. 
     There are several limitations to the current application of DHF:
     1) Patient selection. Patients, for known systems DHF, must have adequate vascular blood flow in order to provide extracorporeal blood flows of 650 ml/min. Most DHF patients have fistulas, however PTFE grafts can provide adequate blood flow. The known systems and procedures can not be used with patients who either do not want larger needles for blood access or do not have a blood access that provides a good enough flow to sustain a delivered flow of at least 550 ml/min.   2) Modification of equipment: As discussed previously, several modifications to existing equipment must be made in order to enable the delivery of DHF. These add risk to the treatment and liability to the clinic that alters the equipment. However, new machines are being produced which have wider TMP and arterial pressure ranges that permit the pressures achieved during DHF.   3) If lower blood flows (&lt;550 ml/min) are used with the existing set up of DHF, there is an increased concern of dialyzer clotting as plasma water is ultrafiltered, thereby hemoconcentrating the blood in the first dialyzer. The current therapy requires full opening of the clamp at low blood flows, which reduces the ultrafiltration capability of the system.   

     BRIEF SUMMARY OF THE INVENTION 
     The present invention provides an improved dialysis apparatus and procedure that mitigate various drawbacks of the type described above. 
     For this purpose, the invention provides an apparatus for use in blood dialysis comprising: 
     first and second dialyzers each containing a semipermeable membrane that divides the dialyzer into a blood compartment and a dialysate compartment, the dialysate compartment of each dialyzer being connectable to a dialysis machine; 
     a blood compartment connecting line connecting the blood compartments of the dialyzers together in series; 
     blood connecting lines for connecting the blood compartments to the vascular system of a patient; and 
     a dialysate compartment connecting unit connecting the dialysate compartments of the dialyzers together in series, wherein 
     the dialysate compartment connecting unit comprises an adjustable flow varying device for controllably setting the rate of the flow of dialysate through the connecting unit, the device being constructed to progressively vary the dialysate flow rate through the connecting unit. 
     The invention also provides a method for performing dialysis on a patient with the apparatus described above, comprising: 
     connecting the dialysate compartments to a dialysis machine; 
     connecting the blood connecting lines to the vascular system of a patient; 
     placing the dialysis machine into operation; and 
     setting the rate of flow of the dialysate by adjusting the flow varying device to establish a selected relative pressure in the dialyzers. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a block diagram of a dialysis apparatus to which the present invention is applied. 
         FIG. 2  is a cross-sectional view taken along the line II—II of FIG.  3 . 
         FIG. 3  is a cross-sectional view taken along line III—III of  FIG. 2  of a first embodiment of a connecting device according to the invention. 
         FIGS. 4 and 5  are views similar to those of  FIGS. 2 and 3 , respectively, of a second embodiment of a connecting device according to the invention. 
         FIG. 6  is a cross-sectional view taken along line VI—VI of FIG.  4 . 
         FIG. 7  shows another embodiment of a connecting device according to the invention. 
         FIG. 8  is a simplified pictorial view showing another embodiment of a connecting device according to the invention. 
     
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       FIG. 1  illustrates the type of dialysis apparatus to which the present invention is applied. This apparatus is composed essentially of two dialyzers  12  and  14  and a dialysis machine  16 , all of which are of conventional type. An exemplary dialyzer that may be used in apparatus according to the invention in disclosed in U.S. Pat. No. 6,117,100. 
     Each dialyzer  12 ,  14  is formed to contain a blood compartment and a dialysate compartment (not shown in detail). These compartments are separated from one another by semipermeable membranes having appropriate selective filtering properties. 
     In apparatus intended to achieve the results of the present invention, the blood flow compartments of dialyzers  12  and  14  are connected together in series, as are the dialysate compartments. Specifically, the dialyzer compartments of dialyzers  12  and  14  are connected together in series by a blood compartment connecting line  20 . Blood connecting lines  24  and  26  are provided to couple the system to the circulatory system of the patient so that blood will flow from the patient via line  24  and be returned to the patient via line  26 . 
     The dialysate compartments of the two dialyzers  12  and  14  are connected together in series by a dialysate compartment connecting unit  30  and the series arrangement of the two dialysate compartments is-connected to dialysis machine  16  by dialysate connecting lines  34  and  36 . Specifically, lines  34  and  36  are connected so that dialysate is pumped from machine  16  through line  36  and is returned to machine  16  through line  34 . Thus, in dialyzers  12  and  14  dialysate flows in counter current to the flow of blood. 
     The performance of the disclosed apparatus, i.e. the effectiveness of the blood cleaning operation, depends, inter alia, on the pressure differential across the membrane separating each blood compartment from the dialysate compartment in the associated dialyzer  12 ,  14 . Machine  16  has a pump mechanism, known as a volumetric control, that insures that the quantity of dialysate entering the dialyzers is equal to that leaving the dialyzers, plus a defined quantity of excess fluid. The excess fluid is to be removed from the patient and represents the quantity of fluid accumulated in the patient&#39;s body since the previous dialysis. 
     According to the present invention, an improved control of these pressure differentials is achieved by constructing unit  30  to allow a progressive, accurately controllable adjustment of the flow resistance provided by that unit, thereby allowing an accurate and progressive adjustment of the relation between the dialysate pressures in dialyzers  12  and  14 . 
     A first embodiment of a dialysate compartment connecting unit is shown in  FIGS. 2 and 3 ,  FIG. 3  being a cross-sectional view taken along line III—III of FIG.  2  and  FIG. 2  being a cross-sectional view taken along the line II—II of FIG.  3 . This unit includes a primary flexible tube  42  that is connected between the dialysate compartments of dialyzers  12  and  14  and provides a primary dialysate flow path. A second tube  44  is connected in parallel with a section of tube  42  and is provided to define a minimum dialysate flow path, as will be explained in detail below. The provision of a minimum flow path having a fixed flow resistance serves to prevent the triggering of a machine alarm and clotting of the blood flow circuit of the dialyzers due to excessive ultrafiltration. 
     Both tubes  42  and  44  extends through a roller clamp device that is composed of a generally U-shaped support member  50  having side walls provided internally with elongated grooves, or slots,  52  and a roller  54  having axial members  56  that are held in grooves  52 . As illustrated, grooves  52  are inclined relative to the longitudinal axis of tube  42  so that when roller  54  is rolled along groves  54 , which is done manually, tube  42  will be progressively constricted. By proper dimensioning of the diameter of roller  54  and of the location of and inclination of grooves  52 , movement of roller  54  along grooves  52  can cause the cross-section of tube  42  to progress from a maximum area, when tube  42  has a round cross section, to a minimum, and even zero, area, when roller  54  is at the lower end of grooves  52 . It will be noted that even if tube  42  is fully constricted so that there is no flow of dialysate therethrough, tube  44  will continue to provide the minimum dialysate flow path to assure continued safe operation of the apparatus. 
     Typically, tube  42  will be made of a flexibly resilient plastic that offers a certain resistance to constriction when roller  54  is advanced downwardly along grooves  52 . This resistance will act to press axial members  56  against the upper edges of grooves  52 , with the result that roller  54  will remain in whatever position along grooves  52  that it is placed by the operator. Thus, it is possible to progressively vary the internal cross-sectional area of tube  42  and, correspondingly, to vary the flow resistance offered by unit  30  and the rate of dialysate flow through the system. As the flow resistance of unit  30  is increased, the pressure at the outlet end of the dialysate compartment of dialyzer  14  will increase and that at the inlet end of the dialysate compartment of dialyzer  12  will decrease. This will affect the exchange operation being carried out in each dialyzer. Specifically, as the flow resistance presented by unit  30  is increased, the rate of ultrafiltration in dialyzer  12  and the rate of backfiltration in dialyzer  14  both increase. 
     A second embodiment of a unit  30  according to the invention is illustrated in  FIGS. 4 and 5 , which contain views similar to those of  FIGS. 2 and 3 , respectively. 
     In the embodiment shown in  FIGS. 4 and 5 , there is only one tube  62 , which is a flexible tube like tube  42 . Tube  62  contains a hollow restrictor rod  64  that will provide a minimum dialysate flow path when tube  62  has been constricted to a maximum extent. Rod  64  is secured in tube  62  by a support element  66  provided with at least one fluid flow passage  68 . 
     This embodiment includes a roller having, in addition to axial members  56 , two lateral parts  72  spaced from one another along the axis of rotation of the roller, and particularly along the axis defined by members  56 , and a central part  74  that has a smaller diameter than lateral parts  72  and is interposed between parts  72 . As is readily apparent from the view of  FIG. 5 , parts  72  and  74  cooperate to enable tube  62  to be substantially completely flattened without imposing any substantial deformation force on rod  64 . Thus, when the roller is at the lowest end of grooves  52 , imposing a maximum deformation on tube  62 , dialysate flow can continue through rod  64  to produce the same result as flow through tube  44  in the embodiment shown in  FIGS. 2 and 3 . 
     According to a further feature of the invention, the roller clamp can be provided with visible markers, or indicia,  80 , as shown in FIG.  5 . Such indicia can also be provided on other roller clamp housings according to the invention, such as housing  50  shown in  FIGS. 2 and 3 . These indicia will provide at least a rough indication of the degree of constriction being imposed on tube  42  or  62 . However, it is preferred that the precise positioning of the roller along grooves  52  be determined on the basis of readings provided by indicators associated with machine  16 . 
       FIG. 6  is a cross-sectional view taken along line VI—VI of  FIG. 4 , showing the details of support element  66  and rod  64 . 
     According to a further embodiment of the invention, restrictor rod  64  and its associated support element  66  could be installed in tube  44  of the embodiment shown in  FIGS. 2 and 3  in order to reduce the cross-sectional area of the minimum dialysate flow path. 
     Another embodiment of a roller clamp assembly according to the invention is shown in  FIG. 7 , which is a view similar to that of  FIGS. 2 and 4 . This embodiment differs from that shown in  FIGS. 2 and 3  essentially in that housing  50  surrounds only flexible tube  42 . This enables housing  50  to be given a simpler structure and ensures that the action of the roller clamp will not affect the cross-sectional area of tube  44 . Here again, rod  64  and its associated support elements  66  can optionally be included in tube  44 . 
     A further embodiment shown in  FIG. 8 , is equipped with a dialysate compartment connecting unit  30  that includes two Y connectors  90  and  92 . Y connector  90  connects a single tube  94  to two parallel tubes  42 ′ and  44 ′. Tube  94  is connected to the outlet end of the dialysate compartment of dialyzer  14 . Tube  42 ′ is a standard tube of a compressible material and is associated with a roller clamp according to the invention that is movable to completely open, partially close, or fully close the flow path through this tube. The roller clamp can be identical to that shown in FIG.  7 . 
     Tube  44 ′ is not compressed and may have a flow restrictor installed therein, such as the flow restrictor shown in  FIGS. 6 and 7 . However, the flow restrictor can be any small diameter device inserted into the flow path so that all fluid entering tube  44 ′ must pass through the restrictor. The restrictor could, for example, be a 2 cm long plastic cylinder with a 2 mm inner diameter that is inserted into the flow path of tube  44 ′ so that all fluid entering tube  44 ′ must pass through the cylinder. 
     When the clamp on tube  42 ′ is fully or partially open, fluid passes through both tubes, divided according to the respective flow resistances of the tubes. Downstream of the restrictor and clamp, the two tubes are again united by the second Y connector  92 , which is attached to the inlet end of the dialysate compartment of dialyzer  12  by a single tube  96 . 
     As in the operation of the other embodiments of the invention, when the clamp is fully closed, all of the dialysate flows through tube  44 ′. The dialysate pressure upstream of unit  30 , in the dialysate compartment of dialyzer  14 , is then very high, while the pressure downstream of unit  30 , in the dialysate compartment of dialyzer  12 , is very low. This permits fluid ultrafiltration from the blood to the dialysate in dialyzer  12  and backfiltration of dialysate to the blood in dialyzer  14 . 
     The dialysate flow through the restrictor provides the pressure differential for large ultrafiltration in dialyzer  12 , yielding additional convective removal of middle weight molecules. A typical middle weight molecule is β2 microglobulin which is approximately 11,800 daltons. The quantity of fluid ultrafiltered in dialyzer  12  is compensated for by backfiltration of dialysate in dialyzer  14 . The volumetric control in the dialysis machine will ensure the balance of fluid, accounting for proper removal of fluid gained by the patient since the preceding dialysis. 
     In all of the embodiments of the invention, the roller clamp enables the user to adjust the flow through the first tube by evaluating the TMP levels. As the roller is rolled, it gradually reduces the flow through the associated tube. The reduction of flow through one tube results in an increase in flow to the second tube, which may be provided with the restrictor. This will alter the pressures as discussed above and enhance ultrafiltration and convective removal of middle molecular weight solutes (i.e. β2 microglobulin). When the TMP approaches the alarm limits, no further constriction, via the roller clamp, should be made. 
     Embodiments of the invention can be applied to at least certain existing dialysis equipment, although it may be desirable to provide different sized dialyzers with different ultrafiltration capabilities and lower dialyzer blood flows. Since it will be possible to variably control the rate of filtration and backfiltration by adjusting the roller clamp, it will be possible to apply this treatment to a larger number of patients with a wide range of attainable blood flows. This will also provide a method for individualizing the treatment for each patient&#39;s needs. 
     A dialysate compartment connecting unit according to the invention will be used in the following manner:
     1. Two dialyzers will be connected together and to a dialysis machine as shown in  FIG. 1 , and will be connected to the patient.   2. The roller clamp will remain fully open as the treatment is initiated.   3. As the blood flow reaches a prescribed level, the roller clamp will be slowly adjusted to increase the filtration and back filtration.   4. The roller clamp should be adjusted so that pressure sensors on the dialysis machine do not alarm. The clinic may decide to shift the calibration of the sensors in order to increase the possible filtration rate without machine alarms. Alternatively, the clinic may decide to maximize the fraction of plasma water that passes through the dialysis membrane to no greater than 25-33% of the blood flow through the machine dependent on hematocrit level, or 50% filtration of the plasma water.   5. The rate of ultrafiltration can be approximated as a product of the Kuf and the transmembrane pressure (TMP) in the dialyzer. Values for these characteristics are commonly found in the medical literature and in the dialyzer manufacturer&#39;s product literature. Kuf is the coefficient of ultrafiltration with the units: cc/hour/mmHg. TMP is the pressure difference between the blood side and the dialysate side of the dialyzer at given blood flows.   6. The roller clamp can be adjusted throughout the treatment if necessary as the hematocrit increases as plasma water (patient weight gain) is removed and the blood becomes more viscous, reducing filtration rate and increasing pressures.   7. After treatment, the roller clamp should be fully opened and the blood flow reduced as the treatment is terminated and the patient is disconnected from the dialysis machine.   

     While the description above refers to particular embodiments of the present invention, it will be understood that many modifications may be made without departing from the spirit thereof. The accompanying claims are intended to cover such modifications as would fall within the true scope and spirit of the present invention. 
     The presently disclosed embodiments are therefore to be considered in all respects as illustrative and not restrictive, the scope of the invention being indicated by the appended claims, rather than the foregoing description, and all changes which come within the meaning and range of equivalency of the claims are therefore intended to be embraced therein.