Abstract:
A dialysis apparatus includes a dialysis liquid circuit for circulating sodium chloride and sodium bicarbonate through a haemodialyzer and a circuit for infusing a patient with at least one solution containing at least one ionic substance “A” absent from the dialysis liquid. The substance “A” has a determined concentration (A)sol in the infusion solution. A dialysance detector determines the actual dialysance “D” of the haemodialyzer for sodium, and a flow rate detector determines the flow rate Qinf of infusion solution such that the concentration of the substance “A” inside the patient&#39;s body tends towards a desired concentration (A)des, as a function of the dialysance “D”, the concentration (A)sol of the substance “A” in the infusion solution and the desired concentration (A)des, A regulator regulates the flow rate of infusion solution, and a controller drives the regulator to control the flow rate of the infusion solution such that this flow rate is substantially equal to the determined flow rate Qinf.

Description:
PRIORITY CLAIMED 
     Applicants claim the right to priority based on French Patent Application No. 97 10670, filed Aug. 21, 1997, in France. This is a continuation of U.S. patent application Ser. No. 09/137,410, filed Aug. 20, 1998, and issued as U.S. Pat. No. 6,325,774 on Dec. 4, 2001, which is incorporated herein by reference. 
    
    
     BACKGROUND OF THE INVENTION 
     The present invention relates to a dialysis apparatus for independently controlling the concentration of at least two ionic substances inside a patient&#39;s body. 
     The kidneys fulfill many functions, including the removal of water, the excretion of catabolites (or waste from the metabolism, for example urea and creatinine), the regulation of the concentration of the electrolytes in the blood (sodium, potassium, magnesium, calcium, bicarbonates, phosphates, chlorides) and the regulation of the acid/base equilibrium within the body, which is obtained in particular by the removal of weak acids (phosphates, monosodium acids) and by the production of ammonium salts. 
     In individuals who have lost the use of their kidneys, since these excretion and regulation mechanisms no longer work, the body accumulates water and waste from the metabolism and exhibits an excess of electrolytes (in particular sodium), as well as, in general, acidosis, the pH of the blood plasma shifting towards 7 (the blood pH normally varies within narrow limits of between 7.35 and 7.45). 
     In order to overcome renal dysfunction, resort is conventionally made to a blood treatment involving extracorporeal circulation through an exchanger having a semipermeable membrane (haemodialyser) in which the patient&#39;s blood is circulated on one side of the membrane and a dialysis liquid, comprising the main electrolytes of the blood in concentrations close to those in the blood of a healthy subject, is circulated on the other side. Through the effect of the physical phenomenon referred to as dialysis, the molecules migrate from the liquid where their concentration is higher to the liquid where their concentration is lower. 
     In conventional dialysis apparatus, the dialysis liquid is prepared by metered mixing of water and two concentrated solutions, the first concentrated solution containing sodium chloride and sodium bicarbonate, and the second concentrated solution containing, calcium chloride, potassium chloride and magnesium chloride as well as acetic acid. The function of the acetic acid is to limit the formation of calcium carbonate and magnesium carbonate precipitates which form undesirabledeposits in the hydraulic circuit of the dialysis apparatus. 
     This conventional way of preparing a dialysis liquid has several drawbacks: 
     the respective concentrations of the various ionic substances involved in the composition of the dialysis liquid cannot be regulated independently of one another, even though this would be desirable at least for sodium, potassium and bicarbonate; 
     for physiological reasons, the acetic acid concentration in the dialysis liquid is necessarily limited, so that carbonated deposits are formed in the hydraulic circuit of the dialysis apparatus. Dialysis apparatus therefore need to be regularly descaled, which places a further burden on their maintenance; 
     the presence of acetic acid in the second solution causes corrosion of the connection and pumping means used for transferring the concentrated solution from the reservoir where it is contained to the mixing zone of the apparatus, where it is diluted in the solution obtained by metered mixing of water and the first solution; 
     use of a dialysis liquid having a pH less than that of blood at the time when certain types of haemodialysers are started up, that is to say at the time when the dialysis liquid compartment of these haernodialysers is filled with dialysis liquid and the blood compartment is filled with diluted blood, seems to be one of the cofactors of certain hypersensitivity reactions. 
     Document EP 0 192 588 describes a dialysis apparatus comprising: 
     means for circulating a dialysis liquid which contains sodium bicarbonate and is free of calcium and magnesium, 
     means for infusing the patient with an infusion solution containing at least calcium and magnesium. 
     With this apparatus, since the ionic substances (bicarbonate, calcium, magnesium) which can form precipitates when they are combined, are separated, it is not necessary to involve acetic acid in the composition of the dialysis liquid. As described, however, this apparatus cannot be used because it does not comprise means for regulating the infusion flow rate which, in particular, would take into account the diffusive transport of calcium and magnesium through the membrane of the dialyser, from the patient&#39;s blood to the dialysis liquid. Now, for safety reasons, it is not envisageable to infuse a patient with a&#39; concentrated calcium solution without being able to regulate the infusion flow rate accurately so that there is neither an excess or deficit of this ionic substance within the patient&#39;s body. 
     SUMMARY OF THE INVENTION 
     The object of the invention is to provide a dialysis apparatus which makes it possible to regulate accurately the flow rate of an infusion liquid containing an ionic substance with a view to making the concentration of this substance inside the patient&#39;s body tend towards a desired concentration. More broadly, the object of the invention is to provide a dialysis apparatus which makes it possible to control separately the concentration of at least two ionic substances inside a patient&#39;s body by means of a dialysis liquid and an infusion liquid. 
     This object is achieved by means of dialysis apparatus comprising: 
     means for circulating a dialysis liquid containing sodium chloride and sodium bicarbonate through a haemodialyser; 
     means for infusing a patient with at least one solution containing at least one ionic substance A (calcium, magnesium, potassium) absent from the dialysis liquid, the substance A having a determined concentration [A]sol in the infusion solution; 
     means for determining the actual dialysance D of the haemodialyser for sodium; 
     means for determining a flow rate Qinf of infusion solution such that the concentration of the substance A inside the patient&#39;s body tends towards a desired concentration [A]des, as a function of the dialysance D, of the concentration [A]sol of the substance A in the infusion solution, and of the desired concentration [A]des; 
     regulating means for regulating the flow rate of infusion solution; 
     control means for driving the means for regulating the flow rate of the infusion solution such that this flow rate is substantially equal to the determined flow rate Qinf. 
     In the dialysis apparatus according to the invention, since the dialysis liquid is free of calcium, magnesium and, optionally, potassium, these substances which are present in the blood migrate by diffusion from the blood to the dialysis liquid in the course of the dialysis session. It is in order to compensate for these diffusive losses that provision is made to infuse the patient with a solution containing these substances. The difficulty resides in the fact that these diffusive losses can vary in the course of a dialysis session lasting several hours, and in the fact that an excess or deficit of potassium, calcium and magnesium in the patient&#39;s blood can lead to serious disorders, in particular cardiac disorders. By virtue of the invention, this difficulty is overcome since the flow rate of the infusion is slaved to the actual dialysance of the treatment system. 
     Moreover, further to remedying the drawbacks of conventional dialysis apparatus mentioned above, the apparatus according to the invention also has the following advantage: provided that the infusion liquid is injected directly into the patient or, downstream of the haemodialyser, into the extracorporeal blood circulation circuit connecting the patient to the haemodialyser, the ionic calcium in the blood migrates by diffusion into the dialysis liquid since the latter is free of calcium. Now, ionic calcium is involved in the sequence of reactions constituting the coagulation process of blood. The extensive calcium depletion of the blood in the haemodialyser therefore partially inhibits the coagulation process, which makes it possible to reduce the amount of anticoagulant usually injected into the extracorporeal blood circulation circuit to prevent blood from coagulating in it. 
     According to one characteristic of the invention, the means for determining the infusion flow rate Qinf comprise calculation means for calculating the infusion flow rate Qinf according to the formula:        Qinf   =     Cl   ×         [   A   ]        des           [   A   ]        sol     -       [   A   ]        des                                  
     where Cl is the clearance of the haemodialyser for the substance A, extrapolated on the basis of the dialysance D for sodium. 
     According to another characteristic of the invention, the infusion solution contains sodium at a determined concentration [Na+]sol. In this case, the apparatus furthermore includes: 
     means for preparing the dialysis liquid, comprising means for regulating the sodium concentration of the dialysis liquid; 
     means for determining the sodium concentration [Na+]dial of the dialysis liquid such that the concentration inside the patient&#39;s body tends towards a desired sodium concentration [Na+]des, as a function of the dialysance D, of the flow rate of the infusion liquid Qinf, of the sodium concentration (Na+]sol of the infusion solution, and of the desired sodium concentration [Na+]des; control means for driving the means for regulating the sodium concentration of the dialysis liquid such that this concentration is equal to the determined concentration [Na+]dial. 
     According to one characteristic of the invention, the means for determining the sodium concentration [Na+]dial of the dialysis liquid comprise calculation means for calculating this concentration according to the formula:            [           Na        +             ]        dial     =         Qinf   D                       (        [           Na        +             ]        des     -       [           Na        +             ]        sol           )       +       [           Na        +             ]        des                              
     Other characteristics and advantages of the invention will become more clearly apparent on reading the following description. 
    
    
     BRIEF DESCRIPTION OF THE DRAWING 
     FIG. 1 is an exemplary haemodialysis system in accordance with the present invention. 
    
    
     DESCRIPTION OF EXEMPLARY EMBODIMENTS 
     The haemodialysis system represented in the figure comprises a haemodialyser  1  having two compartments  2 ,  3  separated by a semipermeable membrane  4 . A first compartment  2  has an inlet connected to a blood withdrawal line  5 , in which a circulation pump  6  is arranged, and an outlet connected to a blood return line  7  in which a bubble trap  8  is inserted. 
     An infusion device, comprising a pump  10  and a balance  11 , is provided for injecting the contents of an infusion liquid bag  9  into the bubble trap  8 . The bag  9  is suspended from the balance  11  and is connected to the bubble trap  8  by a line  12  in which the infusion pump  10  is arranged. The balance  11  is used to drive the pump  10  such that the flow rate of the infusion liquid is equal to a target flow rate. 
     The second compartment  3  of the haemodialyser  1  has an inlet connected to a feed line  12  for fresh dialysis liquid, and an outlet connected to a discharge line  13  for spent liquid (dialysis liquid and ultrafiltrate). 
     The feed line  12  connects the haemodialyser  1  to a device  14  for preparing dialysis liquid (e.g., a dialysis liquid generator). As described below, the dialysis liquid generator is capable of varying the sodium concentration and the bicarbonate concentration. The dialysis liquid generator may comprise, for example, a main line  15  to which two secondary branch lines  16 ,  17  are connected in series. The upstream end of the main line  15  is intended to be connected to a source of running water. Each secondary line  16 ,  17  comprises connection means for fitting a cartridge  18 ,  19  containing a salt in granular form (e.g., sodium and bicarbonate). A pump  20 ,  21  is arranged in each secondary line  16 ,  17  downstream of the corresponding cartridge  18 ,  19  in order to circulate the liquid from the main line through it. Each pump  20 ,  21  is driven on the basis of comparison between  1 ) a target conductivity value for the mixture of liquids formed where the main line  15  joins the downstream end of the secondary line  16 ,  17  and  2 ) the value of the conductivity of this mixture measured by means of a conductivity probe  22 ,  23  arranged in the main line  15  immediately downstream of the junction between the main line  15  and the downstream end of the secondary line  16 ,  17 . 
     The feed line  12  forms an extension of the main line  15  of the device  14  for preparing dialysis liquid. Arranged in this feed line, in the direction in which the liquid circulates, there are a first flow meter  24  and a first circulation pump  25 . 
     The downstream end of the discharge line  13  for spent liquid is intended to be connected to the drain. Arranged in this line, in the direction in which the liquid circulates, there are a second circulation pump  26  and a second flow meter  27 . An extraction pump  28  is connected to the discharge line  13 , upstream of the second circulation pump  26 . The extraction pump  28  is driven in such a way that its delivery rate is equal to a target value for the ultrafiltration rate in the haemodialyser  1 . 
     The feed line  12  and the discharge line  13  are connected by first and second branch lines  29 ,  30 , which are connected together by a junction line  31  in which a conductivity probe  32  is arranged. These branch  29 ,  30  and junction  31  lines and the conductivity probe  32  form a device for measuring the conductivity of the fresh and spent dialysis liquid which is used, as will be explained below, to determine the actual dialysance (or clearance) of the system for sodium or another substance of similar molecular weight. The first branch line  29  is connected to the feed line  12 , downstream of the first circulation pump  25 , via a first three-way valve  33 , and is connected to the discharge line  13 , upstream of the second circulation pump  26 , via a second three-way valve  34 . The second branch line  30  and the junction line  31  are connected via a third three-way valve  35 . 
     The haemodialysis system represented in FIG. 1 also comprises a calculation and control unit  36 . This unit is connected to a user interface (alphanumeric keyboard)  37  through which it receives the information output by the measuring instruments of the system, for example the flow meters  24 ,  27 , the conductivity probes  22 ,  23 ,  32  and the balance  11 . On the basis of the instructions received and the operating modes and algorithms which have been programmed, it drives the active components of the system, such as the pumps  6 ,  10 ,  20 ,  21 ,  25 ,  26 ,  28  and the valves  33 ,  34 ,  35 . 
     In the embodiment of the invention which is represented in the figure, 
     the cartridge  18  contains only sodium bicarbonate; 
     the cartridge  19  contains only sodium chloride; and 
     the infusion liquid bag  9  contains a solution of calcium, magnesium and potassium chloride. The bag  9  optionally also contains sodium. 
     The haemodialysis apparatus which has just been described operates as follows. 
     Via the user interface  37 , an operator communicates target values corresponding to the various parameters of the treatment (prescription) to the control unit  36 , namely the flow rate of blood Qb, the flow rate of the dialysis liquid Qd, the total weight loss WL (amount of plasma fluid to be withdrawn from the patient by ultrafiltration), the total duration T of the session, the bicarbonate concentration [HCO3 − ]dial of the dialysis liquid (which should make it possible for the bicarbonate concentration inside the patient&#39;s body to tend towards a desired concentration [HCO3 − ]des), the sodium concentration [Na + ]dial of the dialysis liquid (which should make it possible for the sodium concentration within the patient&#39;s body to tend towards a desired concentration ([Na+]des), the potassium concentration [K + ]sol of the infusion solution, and the potassium concentration [K + ]des to which the concentration inside the patient&#39;s body should tend. After a sodium bicarbonate cartridge  18  and a sodium chloride cartridge  19  have been connected to the corresponding lines  16 ,  17  of the device  14  for preparing dialysis liquid, the dialysis liquid circuit is filled with dialysis liquid. In order to do this, the main line  15  is connected to a source of running water and the pumps  20 ,  21 ,  25 ,  26  are turned on. The pumps  20  and  21  are regulated by the control unit  36  such that the bicarbonate concentration and the sodium concentration of the dialysis liquid are equal to the corresponding target values [HCO3 − ]dial and [Na + ]dial. The pumps  25 ,  26  for circulating dialysis liquid are regulated by the control unit  36  such that the delivery rate of the pump  25  located upstream of the haemodialyser  1  is equal to the target flow rate Qd (for example 500 ml/min) and the delivery rate of the pump  26  located downstream of the haemodialyser  1  is such that the flow rates measured by the flow meters  24 ,  27  are equal. The three-way valves  33 ,  34 ,  35  of the device for measuring the conductivity of the dialysis liquid are arranged such that the conductivity probe  32  is normally exposed to fresh dialysis liquid (the path of the dialysis liquid successively following the lines  12 ,  29 ,  31 ,  30 ,  12  and  13 ). In order to rinse and initially fill all the lines for fresh dialysis liquid, the valves  33 ,  34  and  35  are turned at least once so that the conductivity probe  32  is exposed to the liquid leaving the haemodialyser (the path of the dialysis liquid successively following, the lines  12 ,  13 ,  30 ,  31 ,  29  and  13 ). 
     At the same time as the dialysis liquid circuit is filled with the dialysis liquid according to the prescription, the extracorporeal blood circulation circuit is rinsed and filled with sterile saline solution. 
     When the dialysis liquid circuit and the blood circuit have been primed, the blood circuit is connected to the patient and the treatment proper can begin: the pumps  20 ,  21  of the device  14  for preparing dialysis liquid, as well as the pumps  25 ,  26  for circulating the dialysis liquid continue to operate as when the circuit is being primed, while the blood pump  6 , the extraction pump  28  and the infusion pump  10  are turned on. The blood pump  6  is regulated to the target flow rate Qb (for example 200 ml/min) and the extraction pump  28  is regulated to a flow rate QUF calculated by the control unit  36 , on the basis of the target values for the total weight loss WL and the total duration of the treatment T. 
     According to the invention, the infusion pump  10  is regulated to a flow rate Qinf calculated by the control unit  36  on the basis of the following formula:              Qinf   =     Cl   ×         [           K        +             ]        des           [           K        +             ]        sol     -       [           K        +             ]        des                   (   1   )                                
     where Cl is the clearance of the haemodialyser  1  for potassium. The infusion pump  10  is regulated accurately by the control unit  36  on the basis of the information supplied by the balance  11 . The actual clearance Cl for potassium is obtained by extrapolation from the actual dialysance for sodium D, which is determined by implementing the following process, in which the successive steps are controlled by the control unit  36 . With the three-way valves  33 ,  34 ,  35  arranged in such a way that the fresh dialysis liquid irrigates the conductivity probe  32 , the conductivity Cd 1 in of the fresh dialysis liquid corresponding to the prescription is measured and stored. The three valves  33 ,  34 ,  35  are then turned so that the conductivity probe  32  is irrigated by the spent liquid, and the conductivity Cd 1 out of this liquid is measured and stored. The delivery rate of the pump  21  for concentrated sodium chloride solution is then modified (increased or decreased) so that the conductivity of the dialysis liquid circulated is slightly different from the conductivity of the dialysis liquid of the prescription. For example, the conductivity of the second dialysis liquid is regulated so as to be 1 mS/cm greater or less than the conductivity of the first dialysis liquid (which is generally of the order of 14 mS/cm). As before, the conductivity Cd 2 in of the second dialysis liquid upstream of the haemodialyser is measured and stored, after which the three-way valves  33 ,  34 ,  35  are again turned so that the conductivity probe  32  is irrigated by the spent liquid, and the conductivity Cd 2 out of the spent liquid is measured and stored. 
     The dialysance for sodium, can then be calculated by applying the following formula:              D   =     Qd   ×         (     Cd1out   -   Cd1in     )     -     (     Cd2out   -   Cd2in     )         Cd2in   -   Cd1in                 (   2   )                                
     where Qd is the flow rate of the dialysis liquid. 
     Another process for calculating the dialysance D on the basis of measurements taken with two dialysis liquids having different conductivities is described in Patent Application EP 0 658 352. 
     In the particular case of treatment by continuous haemodialysis, in which the flow rate of the dialysis liquid is very much less than the blood flow rate (of the order of three times), the flow rate Qinf of the infusion solution can be calculated at any time by applying the formula:              Qinf   =           [           K        +             ]        des         [           K        +             ]        sol       ×   Qout             (   3   )                                
     where Qout is the flow rate of spent liquid leaving the haemodialyser, which is equal to the sum of the flow rate of fresh dialysis liquid, as determined by the circulation pumps  25 ,  26 , and the flow rate of the extraction pump  28 . 
     EXAMPLE 1 
     The target to be achieved, in terms of potassium concentration [K + ]des inside the body is 2 mEq/l. 
     A blood-isotonic infusion liquid is chosen, in which the relative proportions of the ions are equal to the desired relative proportions for the same ions inside the patient&#39;s body. The infusion liquid may, for example, have the following composition: 
     
       
         [K + ]=42 mEq/l 
       
     
     
       
         [Mg ++ ]=31.3 mEq/l 
       
     
     
       
         [Ca ++ ]=73.5 mEq/l 
       
     
     
       
         [Cl − ]=147 mEq/l 
       
     
     If the actual dialysance D is, for example, 150 ml/min, the infusion flow rate which the control unit calculates by means of formula (1) and imposes on the infusion pump  10  is 0.45 l/h. 
     According to the invention, the intention is to be able to use the dialysis apparatus that has just been described to carry out a haemodiafiltration treatment with a high flow rate of infusion liquid (more than 1 1/h). In this case, it is not possible to use a blood-isotonic infusion liquid containing only potassium, calcium and magnesium chloride (like the one described in Example 1) because this would lead to the patient becoming overloaded with these ionic substances. 
     It is therefore necessary to envisage the use of a substitute liquid in which the potassium, calcium and magnesium concentrations are lower and which furthermore contains sodium so as to remain isotonic with blood. The problem then encountered is of regulating the sodium concentration of the dialysis liquid while taking account of the variable-rate infusion of an infusion liquid containing sodium, so that the patient&#39;s body tends towards a desired sodium concentration [Na+]des. 
     According to the invention, the delivery rate of the pump  21  for concentrated sodium chloride solution is adjusted continuously so that the sodium concentration [Na+]dial of the dialysis liquid, as measured by the conductivity probe  23 , can make the sodium concentration inside the patient&#39;s body tend towards a desired value [Na+]des. The sodium concentration [Na+]dial of the dialysis liquid is calculated by the calculation unit  36  on the basis of the dialysance D of the haemodialyser for sodium, the infusion flow rate Qinf, the sodium concentration [Na+]sol of the infusion solution, and the desired sodium concentration [Na+]des towards which the patient&#39;s body should tend. It can be calculated by applying the following formula:                  [           Na        +             ]        dial     =         Qinf   D                       (        [           Na        +             ]        des     -       [           Na        +             ]        sol           )       +       [           Na        +             ]        des               (   4   )                                
     EXAMPLE 2 
     The target to be achieved, in terms of the potassium concentration [K + ]des inside the body is 2 mEq/l. 
     The target to be achieved, in terms of the sodium concentration [Na + ]des inside the body is 140 mEq/l. 
     The desired infusion flow rate, is about 1 l/h. 
     A blood-isotonic infusion liquid is chosen, in which the relative proportions of the ions are equal to the desired relative proportions for the same ions inside the patient&#39;s body. The infusion liquid may, for example, have the following composition: 
     
       
         [K + ]=20 mEq/l 
       
     
     
       
         (Mg ++ ]=15 mEq/l 
       
     
     
       
         [Ca ++ ]=35 mEq/l 
       
     
     
       
         [Na + ]=77 mEq/l 
       
     
     
       
         [Cl − ]=147 mEq/l 
       
     
     If the actual dialysance D is, for example, 150 ml/min, the infusion flow rate which the control unit  36  calculates by means of formula (1) and imposes on the infusion pump  10  is 1 l/h. Furthermore, the delivery rate which the control unit  36  imposes on the pump  21  for concentrated sodium chloride solution is such that the sodium concentration [Na+]dial of the dialysis liquid is equal to 154.8 mEq/l (concentration by means of formula (4)). 
     EXAMPLE 3 
     The target to be achieved, in terms of the potassium concentration [K + ]des inside the body is 2 mEq/l. 
     The target to be achieved, in terms of the sodium concentration [Na + ]des inside the body is 140 mEq/l. 
     The desired infusion flow rate is about 2 l/h. 
     A blood-isotonic infusion liquid is chosen in which the relative proportions of the ions are equal to the desired relative proportions for the same ions inside the patient&#39;s body. The infusion liquid may, for example, have the following composition: 
     
       
         [K + ]=10 mEq/l 
       
     
     
       
         [Mg ++ ]=7.5 mEq/l 
       
     
     
       
         [Ca ++ ]=17.5 mEq/l 
       
     
     
       
         [Na + ]=112 mEq/l 
       
     
     
       
         [Cl − ]=147 mEq/l 
       
     
     If the actual dialysance D is, for example, 150 ml/min, the infusion flow rate which the control unit  36  calculates by means of formula (1) and imposes on the infusion pump  10  is 2.25 l/h. Furthermore, the delivery rate which the control unit  36  imposes on the pump  21  for concentrated sodium chloride solution is such that the sodium concentration [Na+]dial of the dialysis liquid is equal to 147 mEq/l (concentration calculated by means of formula (4)). 
     EXAMPLE 4 
     The target to be achieved, in terms of the potassium concentration [K + ]des inside the body, is 2 mEq/l. 
     The target to be achieved, in terms of the sodium concentration [Na + ]des inside the body, is 140 mEq/l. 
     The desired infusion flow rate is about 4.5 l/h. 
     A blood-isotonic infusion liquid is chosen, in which the relative proportions of the ions are equal to the desired relative proportions for the same ions inside the patient&#39;s body. The infusion liquid may, for example, have the following composition: 
     
       
         [K + ]=6 mEq/l 
       
     
     
       
         [Mg ++ ]=4.5 mEq/l 
       
     
     
       
         [Ca ++ ]=10.5 mEq/l 
       
     
     
       
         [Na + ]=126 mEq/l 
       
     
     
       
         [Cl − ]=147 mEq/l 
       
     
     If the actual dialysance D is, for example, 150 ml/min, the infusion flow rate which the control unit  36  imposes on the infusion pump  10  is 4.5 l/h. Furthermore, the delivery rate which the control unit  36  imposes on the pump  21  for concentrated sodium chloride solution is such that the sodium concentration [Na+]dial of the dialysis liquid is equal to 147 mEq/l (concentration calculated by means of formula (4)). 
     In the above examples, the target to be achieved was defined in terms of the potassium concentration [K+]des inside the body. It is obvious that, when calcium or magnesium are considered as the critical substance for a certain patient, the infusion pump  10  will be regulated on the basis of a target defined in terms of the desired calcium [Ca ++ ]des or magnesium [Mg ++ ]des concentration inside the patient&#39;s body. 
     Variants may be made to the invention which has just been described. 
     In the embodiment which was described above, only one of the ionic substances contained in the infusion liquid can be metered accurately inside the body. This is due to the fact that only one infusion solution is used, containing all the ionic substances to be infused. If it is desired to meter several ionic substances accurately, it is sufficient to use several infusion liquid bags, each containing a single ionic substance to be metered, and to provide a corresponding number of infusion means (balance and pump). It is also possible to use only a single balance, from which the various bags are suspended, and only a single pump which is associated with distribution means for in turn connecting each bag and the extracorporeal blood circulation circuit according to a determined time sequence. 
     Instead of a single conductivity probe, to which the fresh dialysis liquid and the spent liquid are successively applied, the dialysis liquid circuit may be equipped with two conductivity probes which are arranged in the dialysis liquid circuit, respectively upstream and downstream of the haemodialyser. The dialysis liquid circuit may also include only one conductivity probe, arranged downstream of the haemodialyser, in which case the two target conductivity values used for driving the concentrate pump  21  in order to prepare the first and second dialysis liquids are substituted in the formula indicated above for the conductivity values measured upstream of the haemodialyser.