Anticoagulation fluid comprising citrate and phosphate

Abstract

The present invention concerns an anticoagulation fluid comprising 10-40 mM citrate and 0.1-4 mM phosphate. The anticoagulation fluid is to be used for regional citrate anticoagulation in an extracorporeal blood circuit. The anticoagulation fluid may be combined with at least one treatment fluid in a dialysis treatment, and it may be included in a system for regional citrate anticoagulation in an extracorporeal blood circuit.

Claims

1. A single compartment bag comprising an anticoagulation fluid for regional citrate anticoagulation in an extracorporeal blood circuit, wherein the anticoagulation fluid in the single compartment bag comprises 18-40 mM basic citrate; 0.1-5 mM acid citrate; 0.5-1.5 mM total calcium; and 0.1-3 mM phosphate, the anticoagulation fluid having a pH between 7.4 and 8.

2. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 20-40 mM basic citrate.

3. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 0.5-2.0 mM phosphate.

4. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 0.8-2 mM phosphate.

5. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 0-150 mM sodium.

6. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 1.5-4 mM calcium, 0-5.0 mM potassium, 0-11 mM glucose, and 0-150 mM sodium.

7. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 18 mM basic citrate.

8. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 0.1 mM acid citrate.

9. The single compartment bag according to claim 6, wherein the anticoagulation fluid comprises 1.5-4.0 mM calcium.

10. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 2.0-3.0 mM total calcium.

11. The single compartment bag according to claim 10, wherein the anticoagulation fluid comprises 2.2-2.4 mM total calcium.

12. The single compartment bag according to claim 1, wherein the anticoagulation fluid further comprises 0.1-11 mM glucose.

13. The single compartment bag according to claim 1, wherein the anticoagulation fluid comprises 0.8-1.2 mM phosphate.

14. A single compartment bag comprising an anticoagulation fluid for regional citrate anticoagulation in an extracorporeal blood circuit, wherein the anticoagulation fluid in the single compartment bag comprises 18-40 mM basic citrate; 0.1-5 mM acid citrate; 0.1-11 mM glucose; and 0.1-3 mM phosphate, the anticoagulation fluid having a pH between 7.4 and 8.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1-8 shows different dialysis systems for regional citrate anticoagulation in an extracorporeal blood circuit.

DEFINITIONS

(2) The term “dialysis therapy” means all types of dialysis treatments both for chronic renal insufficiency and acute renal insufficiency.

(3) The term “CRRT” means a continuous renal replacement therapy and this type of treatment mode is used in case of acute renal insufficiency or in case of chronic renal insufficiency when using a wearable artificial kidney system.

(4) The term “filter” means a unit comprising semipermeable membranes. This unit may also be called a semipermeable membrane, a dialyzer, a dialysis filter or a dialysis membrane.

(5) The term “anticoagulation fluid” means a fluid which is intended to provide for the anticoagulation effect within the extracorporeal blood circuit and which is intended to be infused within the extracorporeal blood circuit.

(6) The term “anticoagulation fluid source” means the source of anticoagulation fluid. The source may be provided as fluid concentrate or in form of dry powder concentrate.

(7) The term “treatment fluid” means a dialysis fluid for perfusion of a filter or an infusion fluid, i.e. a fluid for pre- or postinfusion. Thus, treatments fluid includes dialysis fluid, infusion fluid, replacement fluid, and substitution fluid.

(8) The term “source of treatment fluid” means the source of treatment fluid, which may be provided as fluid concentrate or in form of dry powder concentrate.

(9) The term “dialysis fluid” means a fluid for perfusion of a filter, on the dialysate side of such a filter, opposite the blood side.

(10) The term “infusion fluid” means a fluid which is infused into the extracorporeal blood circuit either for predilution, i.e. infused into the extracorporeal blood flow before the blood enters the filter or for postdilution, i.e. infused into the extracorporeal blood flow after the blood has exited the filter and before the blood is returned to the patient. Infusion fluids are normally also named as replacement fluids, substitution fluids or hemofiltration fluids.

(11) The term “total calcium concentration” means the total amount of calcium present in a fluid, thus representing the sum of calcium present as ionized, complex bound and protein bound calcium.

(12) The term “citrate” means citric acid or any salt thereof. The salt may be formed with sodium, magnesium or potassium. The sodium citrate may be present as trisodium citrate, disodium hydrogencitrate, or monosodium dihydrogencitrate.

(13) The term “basic citrate” means herein the tri-form of the citrate, thus the salt of C.sub.6H.sub.5O.sub.7.sup.3−. This salt may be formed with any of sodium, magnesium or potassium.

(14) The term “acid citrate” means herein citric acid or the intermediate salt forms of the acid, thus the salt of hydrogen citrate and dihydrogen citrate, respectively. The acid citrate salts may be formed with any of sodium, magnesium or potassium.

(15) The term “phosphate” means phosphoric acid or any salt thereof. The salt may be formed with sodium, magnesium, or potassium, The component may be added as phosphate (PO.sub.4.sup.3−), hydrogenphosphate (HPO.sub.4.sup.2−) or dihydrogen phosphate (H.sub.2PO.sub.4.sup.−). Examples of salts are trisodium phosphate, disodium hydrogenphosphate, monosodium dihy drogenphosphate.

DETAILED DESCRIPTION OF THE INVENTION

(16) When patients receive continuous dialysis therapy, phosphate will be lost over the semipermeable membrane and administration of phosphate by intravenous routes must be carried out with great caution, as it is difficult to decide the correct amount of phosphate to be administered to the patient. If too much phosphate is administered hyperphosphatemia might develop, having serious consequences for the patient, for example hypocalcaemia, metastatic calcification and hypotension, and if too little phosphate is administered the hypophosphatemia is not corrected.

(17) The regional anticoagulation systems of today with citrate as anticoagulant added in large volumes of anticoagulation fluids limits the amounts of available volume of the treatment fluids. In order to safeguard a proper phosphate balancing throughout the renal replacement treatment, the amount of phosphate needs to be balanced within as many of the used fluids as possible. By adding a balancing concentration of phosphate to at least one of the fluids, especially within the anticoagulation fluid, the phosphate level within the patient is better balanced throughout the treatment, and intravenous administration of phosphate may thereby be omitted, or at least reduced.

(18) The anticoagulation fluid of the present invention comprises basic citrate in an amount of 10-40 mM; acid citrate in an amount of 0-5 mM; and phosphate in an amount of 0.1-4 mM. For example, the concentration of basic citrate may be selected to be 10, 12, 15, 18, 20, 22, 25, 30, 35 or 40 mM, which optionally can be combined with an amount of acid citrate, such as 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, or 5 mM acid citrate.

(19) Phosphate may be included in an amount of 0.1 to 4 mM. For example, the anticoagulation fluid comprises phosphate in an amount of 0.1, 0.6, 0.7, 0.8, 0.9, 1.0, 1.1, 1.2, 1.3, 1.4, 1.5, 2, 2.5, 3, 3.5, or 4 mM.

(20) The concentration of basic citrate and phosphate can be selected within the ranges, however it is advisable to combine a high concentration of basic citrate and a high level of phosphate, and in the same way, to include a lower concentration of phosphate in an anticoagulation fluid comprising lower amount of citrate. Examples of anticoagulation fluids comprises 10 mM basic citrate in combination with 1 mM phosphate, or 40 mM basic citrate in combination with 4 mM phosphate.

(21) Further, an embodiment of the invention is an anticoagulation fluid comprising citrate and phosphate in concentrations as above, and in addition also comprises 0-150 mM sodium (Na.sup.+). The anticoagulation fluid may comprise the sodium in a physiological amount.

(22) The anticoagulation fluid of the invention has a pH between 6 and 8, preferably pH between 6.5 and 8. More preferably, the pH of the anticoagulation fluid may be between 7 and 8, such as 7.4, thus physiological pH. The pH can be adjusted by addition of a suitable acid, for example hydrochloric acid (HCl).

(23) A further embodiment of the invention is an anticoagulation fluid comprising, in addition to the basic citrate and the phosphate, 0-1.5 mM magnesium, 0-4 mM calcium, 0-5.0 mM potassium, 0-11 mM glucose, and 0-150 mM sodium. An anticoagulation fluid as defined herein comprises 10-40 mM basic citrate; 0-5 acid citrate; 0.1-4 mM phosphate; 0-1.5 mM magnesium, 0-4 mM calcium, 0-5.0 mM potassium, 0-11 mM glucose, and 0-150 mM sodium. The anticoagulation fluid may be a physiological fluid.

(24) The present invention concerns an anticoagulation fluid to be used as part of a multipart fluid system for dialysis therapy, wherein the multipart fluid system comprises an anticoagulation fluid and at least one treatment fluid from the group consisting of dialysis fluid and infusion fluids.

(25) In one embodiment of the invention the anticoagulation fluid is used a part of a multipart fluid system for dialysis therapy. This multipart fluid system comprises the anticoagulation fluid and at least one treatment fluid from the group consisting of dialysis fluid and infusion fluids.

(26) In one embodiment of the multipart fluid system the anticoagulation fluid comprises 10-40 mM citrate and 0.1-2.0 mM phosphate.

(27) The treatment fluid to be combined with the anticoagulation fluid according to the invention may be a commercial available treatment fluid. An example is Hemosol BO. This is a treatment fluid containing Sodium 140 mM; Calcium 1.75 mM; Magnesium 0.5 mM; Potassium 0 mM; bicarbonate 32 mM; Lactate 3 mM; Glucose 0 mM; and chloride 109.5 mM.

(28) Also phosphate containing treatment fluids may be combined with the anticoagulation fluid described herein.

(29) Medical solutions suitable as treatment fluids are described in WO2006/041409A1. One of the herein described ready-for-use solutions comprises the following: Sodium 140 mM; Calcium 1.25 mM; Magnesium 0.6 mM; Potassium 4 mM; bicarbonate 30 mM; phosphate (HPO.sub.4.sup.2) 1.2 mM; Glucose 5.0 mM; and chloride 115.9 mM.

(30) Another treatment fluid, ready-for-use described contains the following: Sodium 140 mM; Calcium 1.5 mM; Magnesium 0.5 mM; Potassium 0 mM; bicarbonate 35 mM; phosphate (HPO.sub.4.sup.2) 1.2 mM; Glucose 0 mM; and chloride 107.2 mM. A further another treatment fluid comprises Sodium 140 mM; Calcium 1.25 mM; Magnesium 0.6 mM; Potassium 4 mM; bicarbonate 0 mM; Lactate 35 mM; phosphate (HPO.sub.4.sup.2) 1.2 mM; Glucose 5.0 mM; and chloride 145.9 mM. Another treatment fluid comprises Sodium 140 mM; Calcium 1.25 mM; Magnesium 0.6 mM; Potassium 4 mM; bicarbonate 6.6 mM; phosphate (HPO.sub.4.sup.2) 1.2 mM; Glucose 5.0 mM; and chloride 114.9 mM.

(31) Said anticoagulation fluid may, according one embodiment of the invention be used together with at least one infusion fluid comprising 0-5 mM total calcium, 0-8 mM citrate and 0.1-2.0 mM phosphate, with the provision that the infusion fluid comprises citrate when the total calcium concentration is 0 mM, or comprises calcium when the citrate concentration is 0 mM.

(32) Said anticoagulation fluid may, according to another embodiment of the invention be used together with a dialysis fluid comprising 0-5 mM total calcium, 0-8 mM citrate and 0.1-2.0 mM phosphate, with the provision that the infusion fluid comprises citrate when the total calcium concentration is 0 mM, or comprises calcium when the citrate concentration is 0 mM.

(33) An example of anticoagulation fluid according to the invention comprises 10-40 mM citrate and 0.1-2.0 mM phosphate, and is to be used together with one or more treatment fluids during a dialysis treatment.

(34) The one or more treatment fluids may comprise 0-5 mM total calcium, 0-8 mM citrate, and 0.1-2.0 mM phosphate.

(35) In one embodiment of the present invention said anticoagulation fluid comprises 0.5-2.0 mM phosphate, preferably 0.6-1.5 mM phosphate, and more preferably 0.8-1.2 mM phosphate. In another embodiment of the present invention said anticoagulation fluid or anticoagulation fluid comprises 10-40 mM citrate, preferably 15-40 mM citrate, and more preferably 20-30 mM citrate. In one embodiment said anticoagulation fluid may further comprise 1.5-4 mM total calcium, preferably 2-3 mM total calcium, more preferably 2.2-2.4 mM total calcium.

(36) In yet another embodiment of the present invention said anticoagulation fluid further comprises 0-1.5 mM magnesium, 0-5.0 mM potassium, 0-11 mM glucose, 130-150 mM sodium. The anticoagulation fluid may also comprise chloride ions, for example in an amount of 0-140 mM chloride.

(37) Further, the anticoagulation fluid may be used together with two infusion fluids, a first infusion fluid comprising 0-5 mM total calcium, 0-8 mM citrate and 0.1-2.0 mM phosphate, with the provision that the infusion fluid comprises citrate when the total calcium concentration is 0 mM, or comprises calcium when the citrate concentration is 0 mM; and a second infusion fluid comprising 0.1-2.0 mM phosphate. In one embodiment said second infusion fluid further comprises 0-5 mM total calcium, 0-8 mM citrate, with the provision that the second infusion fluid comprises citrate when the total calcium concentration is 0 mM, or comprises calcium when the citrate concentration is 0 mM.

(38) Also, the anticoagulation fluid may according to even another embodiment of the invention be used together with at least one infusion fluid comprising 0-5 mM total calcium, 0-8 mM citrate and 0.1-2.0 mM phosphate, with the provision that the infusion fluid comprises citrate when the total calcium concentration is 0 mM, or comprises calcium when the citrate concentration is 0 mM; and a dialysis fluid comprising 0.1-2.0 mM phosphate. In one embodiment said dialysis fluid further comprises 0-5 mM total calcium, 0-8 mM citrate, with the provision that the dialysis fluid comprises citrate when the total calcium concentration is 0 mM, or comprises calcium when the citrate concentration is 0 mM.

(39) The anticoagulation fluid may according to one embodiment of the invention be used together with at least one infusion fluid comprising 2-8 mM citrate.

(40) The anticoagulation fluid may according to another embodiment of the invention be used together with a dialysis fluid comprising 2-8 mM citrate.

(41) The anticoagulation fluid may according to another embodiment of the invention be used together with at least one infusion fluid comprising 2-8 mM citrate and 0.1-2.0 mM phosphate.

(42) The anticoagulation fluid may according to a further embodiment of the invention be used together with a dialysis fluid comprising 2-8 mM citrate and 0.1-2.0 mM phosphate.

(43) The anticoagulation fluid may according to one embodiment of the invention be used together with at least one infusion fluid comprising 2-8 mM citrate and 0.1-2.0 mM phosphate; and a dialysis fluid comprising 2-8 mM citrate and 0.1-2.0 mM phosphate.

(44) The anticoagulation fluid may according to one embodiment of the invention be used together with at least one infusion fluid comprising 1-5 mM total calcium.

(45) The anticoagulation fluid may according to another aspect of the invention be used together with a dialysis fluid comprising 1-5 mM total calcium.

(46) The anticoagulation fluid may also be used together with at least one infusion fluid comprising 2-8 mM citrate and 1-5 mM total calcium.

(47) The anticoagulation fluid may also be used together with a dialysis fluid comprising 2-8 mM citrate and 1-5 mM total calcium.

(48) The anticoagulation fluid may also be used together with at least one infusion fluid comprising 2-8 mM citrate and 1-5 mM total calcium; and a dialysis fluid comprising 2-8 mM citrate and 1-5 mM total calcium.

(49) The anticoagulation fluid may in one embodiment comprise 0.5-2.0 mM phosphate, preferably 0.6-1.5 mM phosphate, and more preferably 0.8-1.2 mM.

(50) The anticoagulation fluid may in one embodiment comprise 10-40 mM citrate, preferably 15-40 mM citrate, more preferably 20-30 mM citrate. Said anticoagulation fluid may in one embodiment comprise 1.5-4 mM total calcium, preferably 2-3 mM total calcium, and most preferably 2.2-2.6 mM mM calcium.

(51) The anticoagulation fluid may in one embodiment further comprise 0-1.5 mM magnesium, 0-5.0 mM potassium, 0-11 mM glucose, and 130-150 mM sodium. Also 0-140 mM chloride may be included in the anticoagulation fluid.

DETAILED DESCRIPTION OF THE DRAWINGS

(52) FIGS. 1 to 8 illustrate different dialysis systems wherein the anticoagulation fluid may be used. In FIG. 1 is shown a first system for citrate anticoagulation in an extracorporeal blood circuit comprising an arterial blood line 1 configured to be connected to a vascular access (not shown) for withdrawing blood from a patient and a venous blood line 2 configured to be connected to the vascular access (not shown) for returning blood to the patient. This system comprises a filter 3 with a dialysate side and a blood side, which blood side is in fluid communication with the arterial blood line 1 and venous blood line 2; a pre-filter infusion line 4 connected to the arterial blood line 1 upstream the filter 3 for infusing an anticoagulation fluid 5 comprising 15-40 mM citrate into blood in the arterial blood line 1; and a post-filter infusion line 6 connected to the venous blood line 2 downstream the filter 3 for infusing an infusion fluid 7 comprising 1.5-8 mM citrate and ≥10 mM bicarbonate into blood in the venous blood line 2. An effluent bag 8 is provided in fluid communication with the dialysate side of the filter 3, to collect the plasma water (ultrafiltrate) withdrawn from the blood passing the filter 3.

(53) In FIG. 2 is shown another embodiment of the system in FIG. 1 with the addition that the dialysate side of the filter 3 is in fluid communication with a dialysis fluid source 9 comprising 1.5-8 mM citrate and ≥10 mM bicarbonate.

(54) In FIG. 3 is shown a second system for citrate anticoagulation in an extracorporeal blood circuit. This system includes an arterial blood line 1 configured to be connected to a vascular access for withdrawing blood from a patient and a venous blood line 2 configured to be connected to the vascular access for returning blood to the patient. This system also comprises a filter 3 with a dialysate side and a blood side, which blood side is in fluid communication with the arterial and venous blood lines, and which dialysate side is in fluid communication with a dialysis fluid source 9 comprising 1.5-8 mM citrate and ≥10 mM bicarbonate and an effluent bag 8 for the spent dialysis fluid and the plasma water (ultrafiltrate) withdrawn from the blood passing the filter 3. The system further comprises a pre-filter infusion line 4 connected to the arterial blood line 1 upstream the filter 3 for infusing an anticoagulation fluid 5 comprising 15-40 mM citrate into the blood in the arterial blood line.

(55) In FIG. 4 is shown a third embodiment of the system for citrate anticoagulation in an extracorporeal blood circuit according to the present invention. This system includes an arterial blood line 1 configured to be connected to a vascular access for withdrawing blood from a patient and a venous blood line 2 configured to be connected to the vascular access for returning blood to the patient. This system further comprises a filter 3 with a dialysate side and a blood side, which blood side is configured in fluid communication with the arterial and venous blood lines. A first pre-filter infusion line 4 is connected to the arterial blood line 1 upstream the filter 3 for infusing an anticoagulation fluid 5 comprising 15-40 mM citrate into blood in the arterial blood line 1. A second pre-filter infusion line 10 is connected to the arterial blood line 1 upstream the filter 3 for infusing an infusion fluid 11 1.5-8 mM citrate and ≥10 mM bicarbonate into blood in the arterial blood line 1. Also here an effluent bag 8 is provided in fluid communication with the dialysate side of the filter 3, for receiving the plasma water (ultrafiltrate) withdrawn from the blood passing the filter 3.

(56) In FIG. 5 is another embodiment of the third system in FIG. 4 shown, which further comprises a post-filter infusion line 6 connected to the venous blood line 2 downstream the filter 3 for infusing an infusion fluid 7 comprising 1.5-8 mM citrate and ≥10 mM bicarbonate into blood in the venous blood line 2.

(57) In FIG. 6 is yet another embodiment of the third system in FIG. 4 shown, wherein the dialysate side of the filter 3 is in fluid communication with a dialysis fluid source 9 comprising 1.5-8 mM citrate and ≥10 mM bicarbonate.

(58) In FIG. 7 is another embodiment of the system in FIG. 6 shown. This system further comprises a post-filter infusion line 6 connected to the venous blood line 2 downstream the filter 3 for infusing an infusion fluid 7 comprising 1.5-8 mM citrate and ≥10 mM bicarbonate into the blood in the venous blood line 2.

(59) In FIG. 8 is another embodiment of the systems above shown, which further comprises a control unit 12 adapted to control the anticoagulation fluid flow rate in relation to the blood flow rate. Such a control unit may be provided in all the systems shown in the different embodiments of FIG. 1-FIG. 7. By having such a control unit 12, the system is monitoring and securing that the amount of citrate within the blood is enough to maintain anticoagulation within the extracorporeal blood circuit.

(60) If 1-5 mM total calcium is present in at least one fluid from the group consisting of a dialysis fluid, an infusion fluid, and an anticoagulation fluid, the systems according to the present invention do not need to comprise any post-filter infusion line connected to the venous blood line 2 downstream the filter 3 for infusion of a fluid comprising >6 mM total calcium.

(61) In the systems according to the invention, pumps are configured to pump blood (pump 13) through the extracorporeal blood circuit, anticoagulation fluid (pump 14) into the extracorporeal blood circuit, infusion fluid (pumps 15a and 15b) into the extracorporeal blood circuit, dialysis fluid (pump 16) into the dialysate side of the filter 3, and plasma liquid (ultrafiltrate) and optional spent dialysis fluid (pump 17) out from the dialysate side of the filter 3 and into the effluent bag 8.

(62) An embodiment of the invention is an anticoagulation fluid comprising citrate and phosphate.

(63) The anticoagulation fluid comprises 10-40 mM citrate, and between 0.1 and 4 mM phosphate.

EXAMPLES

(64) By way of example, and not limitation, the following examples identify a variety of anticoagulation fluids comprising citrate and phosphate. Also multipart fluid systems including the anticoagulation fluids are shown.

(65) The anticoagulation fluid comprises basic citrate in a concentration of 10-40 mM, acid citrate in a concentration of 0-5 mM, phosphate in a concentration of 0.6-4 mM, and sodium (Na.sup.+) in a concentration of 0-150 mM.

(66) The anticoagulation fluid has a pH of between 6 and 8.

Example 1

(67) The anticoagulation fluid according to this example comprises the following components:

(68) Basic citrate (mM): 10

(69) Phosphate (mM): 0.8

(70) Sodium (Na.sup.+) (mM): 140

Example 2

(71) The anticoagulation fluid according to this example comprises the following components:

(72) Basic citrate (mM): 12

(73) Phosphate (mM): 0.8

(74) Sodium (Na.sup.+) (mM): 140

Example 3

(75) The anticoagulation fluid according to this example comprises the following components:

(76) Basic citrate (mM): 15

(77) Sodium (Na.sup.+) (mM): 140

Example 4

(78) The anticoagulation fluid according to this example comprises the following components:

(79) Basic citrate (mM): 18

(80) Phosphate (mM): 0.8

(81) Sodium (Na.sup.+) (mM): 140

Example 5

(82) The anticoagulation fluid according to this example comprises the following components:

(83) Basic citrate (mM): 20

(84) Phosphate (mM): 0.8

(85) Sodium (Na.sup.+) (mM): 140

Example 6

(86) The anticoagulation fluid according to this example comprises the following components:

(87) Basic citrate (mM): 22

(88) Phosphate (mM): 0.8

(89) Sodium (Na.sup.+) (mM): 140

Example 7

(90) The anticoagulation fluid according to this example comprises the following components:

(91) Basic citrate (mM): 25

(92) Phosphate (mM): 0.8

(93) Sodium (Na.sup.+) (mM): 140

Example 8

(94) The anticoagulation fluid according to this example comprises the following components:

(95) Basic citrate (mM): 30

(96) Phosphate (mM): 0.8

(97) Sodium (Na.sup.+) (mM): 140

Example 9

(98) The anticoagulation fluid according to this example comprises the following components:

(99) Basic citrate (mM): 10

(100) Phosphate (mM): 0.6

(101) Sodium (Na.sup.+) (mM): 140

Example 10

(102) The anticoagulation fluid according to this example comprises the following components:

(103) Basic citrate (mM): 12

(104) Phosphate (mM): 0.6

(105) Sodium (Na.sup.+) (mM): 140

Example 11

(106) The anticoagulation fluid according to this example comprises the following components:

(107) Basic citrate (mM): 15

(108) Phosphate (mM): 0.6

(109) Sodium (Na.sup.+) (mM): 140

Example 12

(110) The anticoagulation fluid according to this example comprises the following components:

(111) Basic citrate (mM): 18

(112) Phosphate (mM): 0.6

(113) Sodium (Na.sup.+) (mM): 140

Example 13

(114) The anticoagulation fluid according to this example comprises the following components:

(115) Basic citrate (mM): 20

(116) Phosphate (mM): 0.6

(117) Sodium (Na.sup.+) (mM): 140

Example 14

(118) The anticoagulation fluid according to this example comprises the following components:

(119) Basic citrate (mM): 22

(120) Phosphate (mM): 0.6

(121) Sodium (Na.sup.+) (mM): 140

Example 15

(122) The anticoagulation fluid according to this example comprises the following components:

(123) Basic citrate (mM): 25

(124) Phosphate (mM): 0.6

(125) Sodium (Na.sup.+) (mM): 140

Example 16

(126) The anticoagulation fluid according to this example comprises the following components:

(127) Basic citrate (mM): 30

(128) Phosphate (mM): 0.6

(129) Sodium (Na.sup.+) (mM): 140

Example 17

(130) The anticoagulation fluid according to this example comprises the following components:

(131) Basic Citrate (mM): 15

(132) Phosphate (mM): 1.0

(133) Sodium (Na.sup.+) (mM): 140

Example 18

(134) The anticoagulation fluid according to this example comprises the following components:

(135) Basic citrate (mM): 18

(136) Phosphate (mM): 1.0

(137) Sodium (Na.sup.+) (mM): 140

Example 19

(138) The anticoagulation fluid according to this example comprises the following components:

(139) Basic citrate (mM): 20

(140) Phosphate (mM): 1.0

(141) Sodium (Na.sup.+) (mM): 140

Example 20

(142) The anticoagulation fluid according to this example comprises the following components:

(143) Basic citrate (mM): 22

(144) Phosphate (mM): 1.0

(145) Sodium (Na.sup.+) (mM): 140

Example 21

(146) The anticoagulation fluid according to this example comprises the following components:

(147) Basic citrate (mM): 25

(148) Phosphate (mM): 1.0

(149) Sodium (Na.sup.+) (mM): 140

Example 22

(150) The anticoagulation fluid according to this example comprises the following components:

(151) Basic citrate (mM): 30

(152) Phosphate (mM): 1.0

(153) Sodium (Na.sup.+) (mM): 140

Example 23

(154) The anticoagulation fluid according to this example comprises the following components:

(155) Basic citrate (mM): 35

(156) Phosphate (mM): 1.0

(157) Sodium (Na.sup.+) (mM): 140

Example 24

(158) The anticoagulation fluid according to this example comprises the following components:

(159) Basic citrate (mM): 15

(160) Phosphate (mM): 1.2

(161) Sodium (Na.sup.+) (mM): 140

Example 25

(162) The anticoagulation fluid according to this example comprises the following components:

(163) Basic citrate (mM): 18

(164) Phosphate (mM): 1.2

(165) Sodium (Na.sup.+) (mM): 140

Example 26

(166) The anticoagulation fluid according to this example comprises the following components:

(167) Basic Citrate (mM): 20

(168) Phosphate (mM): 1.2

(169) Sodium (Na.sup.+) (mM): 140

Example 27

(170) The anticoagulation fluid according to this example comprises the following components:

(171) Basic citrate (mM): 40

(172) Phosphate (mM): 1.2

(173) Sodium (Na.sup.+) (mM): 140

Example 28

(174) The anticoagulation fluid according to this example comprises the following components:

(175) Basic Citrate (mM): 18

(176) Phosphate (mM): 1.5

(177) Sodium (Na.sup.+) (mM): 140

Example 29

(178) The anticoagulation fluid according to this example comprises the following components:

(179) Basic citrate (mM): 20

(180) Phosphate (mM): 1.5

(181) Sodium (Na.sup.+) (mM): 140

Example 30

(182) The anticoagulation fluid according to this example comprises the following components:

(183) Basic Citrate (mM): 30

(184) Phosphate (mM): 1.5

(185) Sodium (Na.sup.+) (mM): 140

Example 31

(186) The anticoagulation fluid according to this example comprises the following components:

(187) Basic citrate (mM): 40

(188) Phosphate (mM): 1.5

(189) Sodium (Na.sup.+) (mM): 140

Example 32

(190) The anticoagulation fluid according to this example comprises the following components:

(191) Basic Citrate (mM): 30

(192) Phosphate (mM): 2

(193) Sodium (Na.sup.+) (mM): 140

Example 33

(194) The anticoagulation fluid according to this example comprises the following components:

(195) Basic citrate (mM): 40

(196) Phosphate (mM): 2

(197) Sodium (Na.sup.+) (mM): 140

Example 34

(198) The anticoagulation fluid according to this example comprises the following components:

(199) Basic Citrate (mM): 30

(200) Phosphate (mM): 3

(201) Sodium (Na.sup.+) (mM): 140

Example 35

(202) The anticoagulation fluid according to this example comprises the following components:

(203) Basic citrate (mM): 40

(204) Phosphate (mM): 3

(205) Sodium (Na.sup.+) (mM): 140

Example 36

(206) The anticoagulation fluid according to this example comprises the following components:

(207) Basic citrate (mM): 30

(208) Phosphate (mM): 4

(209) Sodium (Na.sup.+) (mM): 140

Example 37

(210) The anticoagulation fluid according to this example comprises the following components:

(211) Basic Citrate (mM): 40

(212) Phosphate (mM): 4

(213) Sodium (Na.sup.+) (mM): 140

(214) The anticoagulation fluid may also comprise further components, like electrolytes and glucose. The following examples identify such anticoagulation fluids.

(215) TABLE-US-00001 Component in anticoagulation Example Example Example Example Example fluid 38 39 40 41 42 Citrate, (mM) 10 12 15 18 20 Phosphate, (mM) 0.8 0.8 0.8 0.8 0.8 Calcium, (mM) 2.4 2.2 2.2 2.2 2.2 Magnesium, (mM) 0.5 0.5 0.5 0.5 0.5 Potassium, (mM) 3 2 2 3 3 Glucose, (mM) 0 0 0 0 0 Sodium, (mM) 140 140 140 140 140 Component in anticoagulation Example Example Example Example Example fluid 43 44 45 46 47 Citrate, (mM) 22 25 25 25 30 Phosphate, (mM) 0.8 0.6 0.8 1.25 0.8 Calcium, (mM) 2.4 2.2 2.5 2.5 2.2 Magnesium, (mM) 0.5 0.7 0.5 0.5 0.8 Potassium, (mM) 3 4 3 3 3 Glucose, (mM) 0 0 0 0 0 Sodium, (mM) 140 140 140 140 140 Component in anticoagulation Example Example Example Example Example fluid 48 49 50 51 52 Citrate, (mM) 30 30 35 40 40 Phosphate, (mM) 1.0 1.25 0.8 1.0 3 Calcium, (mM) 2.4 2.5 2.2 2.3 2.5 Magnesium, (mM) 0.5 0.5 0.7 0.5 0.5 Potassium, (mM) 3 3 3 2 3 Glucose, (mM) 0 0 0 0 0 Sodium, (mM) 140 140 140 140 140

(216) Evaluations

(217) The new anticoagulation fluids according to the invention are intended to be used as a part in a multipart fluid system, and in a system for regional citrate anticoagulation. The fluids have been evaluated by use of simulation program developed in-house by Gambro. It computes equilibrium concentrations of species present in plasma and fluids used for dialysis by use of equilibrium constants (SCD base 2001.sup.1). Simulations according to system shown in FIG. 7. The species (electrolytes, albumin and formed complexes) taken into account are shown in Table 1.

(218) TABLE-US-00002 TABLE 1 Normal plasma concentration of electrolytes and albumin together with the complexes taken into account formed with Ca.sup.2+ and Mg.sup.2+ Normal plasma total conc (mM) Complex formation with Ca.sup.2+ Specie (Kratz 1998.sup.2) and Mg.sup.2+ Ca.sup.2+ 2.1-2.6 (1.1-1.3 ionized) Mg.sup.2+ 0.7-1.0 Na.sup.+ 135-145 Cl.sup.− 100-108 HCO.sub.3.sup.−, bicarbonate, 22-26 CaHCO.sup.3+, MgHCO.sub.3.sup.+ bic Phosphate, HPO.sub.4.sup.2−; 0.7-1.0 CaHPO.sub.4, MgHPO.sub.4 H.sub.2PO.sub.4.sup.− C.sub.6H.sub.5O.sub.7.sup.3−, citrate, cit 0.1-0.3 (infants, Ca-cit.sup.−, Ca-cit.sub.2.sup.4−, Mg-cit.sup.−. Ames1950.sup.3) Mg-cit.sub.2.sup.4− Albumin, alb 0.5-0.6 Alb-Ca.sub.n, alb-Mg.sub.n, n = 1-10

(219) The transport of each species is governed by its mobility and the flow rates of plasma and dialysis fluid. Values for the mobility of different species are found in literature. The transport of ions is also affected by the demand for electroneutrality, which is expressed as the development of a membrane potential. In order to handle the effects of complex formations and albumin binding, the dialyzer is split up into a number of segments and the transport calculations are performed in an iterative manner. The transport across the dialyzer membrane in one segment leads to a new equilibrium for the complex formation and albumin binding, which forms the input to the next segment for the next iteration. About 30 iterations are needed to find the equilibrium concentrations along the entire dialyzer.

(220) The requirements of the treatments are: 1. An adequate dialysis treatment 2. A sufficient anticoagulant effect, i.e. the ionized calcium through the blood side of the filter (dialyzer) must be 0.2-0.5 mM, preferably 0.3-0.4 (according to literature) 3. The plasma concentration of phosphate when returned to the patient has to be at normal level, i.e. about 0.7-1.0 mM. 4. The total plasma concentration of calcium when returned to the patient has to be at normal level, i.e. about 2.5 mM. Other electrolyte concentration levels must also be satisfactory.

(221) In the following examples different multipart systems are presented. These have been evaluated in accordance with the above. The flow rates used at the evaluation is presented, they are denoted and explained as follows:

(222) Qb—blood flow rate from patient;

(223) Qpbp—pre blood pump flow rate;

(224) Qpre—pre-filter treatment fluid rate;

(225) Qpost—post filter treatment fluid flow rate; and

(226) Qd—flow rate of dialysis fluid.

Example A

(227) TABLE-US-00003 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 30 0 4 Phosphate, (mM) 1.0 0.6 1.0 Calcium, (mM) 2.4 2.3 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(228) TABLE-US-00004 TABLE A The result with multipart system according to Example A, with Qb 120 ml/min, Qpbp 16.0 ml/min, Qpre 0.0 ml/min, Qpost 4.8 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.29 Phosphate, total 1.06 Calcium, total 2.26 Calcium, ionized 0.43 Bicarbonate (total CO.sub.2) 18.49 Bicarbonate + citrate 31.37 pH 7.60

Example B

(229) TABLE-US-00005 Anticoagulation Infusion fluid for Dialysis Component fluid preinfusion fluid Citrate, (mM) 30 4 4 Phosphate, (mM) 1.0 0.6 1.0 Calcium, (mM) 2.4 0 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(230) TABLE-US-00006 TABLE B The result of Example B, with Qb 120 ml/min, Qpbp 16.0 ml/min, Qpre 0.0 ml/min, Qpost 4.8 ml/min, Qdi 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.54 Phosphate, total 1.06 Calcium, total 2.12 Calcium, ionized 0.38 Bicarbonate (total CO.sub.2) 18.49 Bicarbonate + citrate 32.11 pH 7.62

Example C

(231) TABLE-US-00007 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 10 4 4 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.4 2.2 2.2 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 35

(232) TABLE-US-00008 TABLE C The result of Example C, with Qb 120 ml/min, Qpbp 48.0 ml/min, Qpre 0.0 ml/min, Qpost 27.2 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 3.70 Phosphate, total 1.03 Calcium, total 2.30 Calcium, ionized 0.52 Bicarbonate (total CO.sub.2) 13.83 Bicarbonate + citrate 24.94 pH 7.59

Example D

(233) TABLE-US-00009 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 12 4 4 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.2 2.2 2.2 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 2 2 2 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 30 30

(234) TABLE-US-00010 TABLE D The result of Example D, with Qb 120 ml/min, Qpbp 40.0 ml/min, Qpre 0.0 ml/min, Qpost 19.2 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 3.96 Phosphate, total 1.02 Calcium, total 2.21 Calcium, ionized 0.46 Bicarbonate (total CO.sub.2) 16.72 Bicarbonate + citrate 28.58 pH 7.62

Example E

(235) TABLE-US-00011 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 18 4 4 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.2 2.2 2.2 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 30 30

(236) TABLE-US-00012 TABLE E The result of Example E Qb 120 ml/min, Qpbp 26.7 ml/min, Qpre 0.0 ml/min, Qpost 5.8 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.32 Phosphate, total 1.01 Calcium, total 2.21 Calcium, ionized 0.42 Bicarbonate (total CO.sub.2) 20.56 Bicarbonate + citrate 33.53 pH 7.63

Example F

(237) TABLE-US-00013 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 25 4 4 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.5 2.3 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 25 25

(238) TABLE-US-00014 TABLE F The result of Example F, with Qb 120 ml/min, Qpbp 26.7 ml/min, Qpre 0.0 ml/min, Qpost 5.8 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.49 Phosphate, total 1.00 Calcium, total 2.28 Calcium, ionized 0.42 Bicarbonate (total CO.sub.2) 21.13 Bicarbonate + citrate 34.60 pH 7.62

Example G

(239) TABLE-US-00015 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 25 3 4 Phosphate, (mM) 1.25 0.6 1.25 Calcium, (mM) 2.5 2.3 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(240) TABLE-US-00016 TABLE G The result of Example G, with Qb 120 ml/min, Qpbp 19.2 ml/min, Qpre 0.0 ml/min, Qpost 1.6 ml/min, Qd 20.0 ml/min Concentration of plasma returning to patient (mmol/l) Citrate, total 4.46 Phosphate, total 1.17 Calcium, total 2.28 Calcium, ionized 0.42 Bicarbonate (total CO.sub.2) 18.31 Bicarbonate + citrate 31.69 pH 7.62

Example H

(241) TABLE-US-00017 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 30 4 4 Phosphate, (mM) 1.25 0.6 1.25 Calcium, (mM) 2.5 2.3 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(242) TABLE-US-00018 TABLE H The result of Example H, with Qb 120 ml/min, Qpbp 16.0 ml/min, Qpre 0.0 ml/min, Qpost 4.8 ml/min, Qd 20.0 ml/min Concentration of plasma returning to patient (mmol/l) Citrate, total 4.54 Phosphate, total 1.15 Calcium, total 2.28 Calcium, ionized 0.41 Bicarbonate (total CO.sub.2) 18.49 Bicarbonate + citrate 32.12 pH 7.61

Example I

(243) TABLE-US-00019 Anticoagulation Infusion fluid Dialysis Component fluid for postinfusion fluid Citrate, (mM) 40 4 4 Phosphate, (mM) 1.0 1.0 1.0 Calcium, (mM) 2.3 2.3 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 2 2 2 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(244) TABLE-US-00020 TABLE I The result of Example I, with Qb 120 ml/min, Qpbp 12.0 ml/min, Qpre 0.0 ml/min, Qpost 8.8 ml/min, Qd 20.0 ml/min. Concentration of plasma returning Result to patient (mmol/l) Citrate, total 4.60 Phosphate, total 1.08 Calcium, total 2.25 Calcium, ionized 0.40 Bicarbonate (total CO.sub.2) 18.67 Bicarbonate + citrate 32.48 pH 7.60

Example J

(245) TABLE-US-00021 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 35 5 5 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.2 2.0 2.0 Magnesium, (mM) 0.7 0.7 0.7 Potassium, (mM) 3 3 3 Glucose, (mM) 0 5.5 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(246) TABLE-US-00022 TABLE J The result of Example J, with Qb 120 ml/min, Qpbp 13.7 ml/min, Qpre 0.0 ml/min, Qpost 7.1 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.90 Phosphate, total 0.99 Calcium, total 2.14 Calcium, ionized 0.36 Bicarbonate (total CO.sub.2) 18.61 Bicarbonate + citrate 33.62 pH 7.61

Example K

(247) TABLE-US-00023 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 25 4 4 Phosphate, (mM) 0.6 0.6 0.6 Calcium, (mM) 2.2 2.0 2.0 Magnesium, (mM) 0.7 0.7 0.7 Potassium, (mM) 4 4 4 Glucose, (mM) 0 5.5 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(248) TABLE-US-00024 TABLE K The result of Example K, with Qb 120 ml/min, Qpbp 19.2 ml/min, Qpre 0.0 ml/min, Qpost 1.6 ml/min, Qd 20.0 ml/min Concentration of plasma returning to patient (mmol/l) Citrate, total 4.48 Phosphate, total 0.92 Calcium, total 2.16 Calcium, ionized 0.40 Bicarbonate (total CO.sub.2) 18.30 Bicarbonate + citrate 31.75 pH 7.61

(249) TABLE-US-00025 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 30 5 5 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.2 2.0 2.0 Magnesium, (mM) 0.8 0.8 0.8 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(250) TABLE-US-00026 TABLE L The result of Example L, with Qb 120 ml/min, Qpbp 16.0 ml/min, Qpre 0.0 ml/min, Qpost 4.8 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.84 Phosphate, total 1.00 Calcium, total 2.15 Calcium, ionized 0.37 Bicarbonate (total CO.sub.2) 18.50 Bicarbonate + citrate 33.00 pH 7.61

Example M

(251) TABLE-US-00027 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 30 4 4 Phosphate, (mM) 1.0 0.6 1.0 Calcium, (mM) 2.4 2.3 2.3 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(252) TABLE-US-00028 TABLE M The result of Example M, with Qb 120 ml/min, Qpbp 16.0 ml/min, Qpre 0.0 ml/min, Qpost 4.8 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.54 Phosphate, total 1.06 Calcium, total 2.26 Calcium, ionized 0.41 Bicarbonate (total CO.sub.2) 18.49 Bicarbonate + citrate 32.11 pH 7.61

Example N

(253) TABLE-US-00029 Anticoagulation Infusion fluid for Dialysis Component fluid postinfusion fluid Citrate, (mM) 35 5 5 Phosphate, (mM) 0.8 0.8 0.8 Calcium, (mM) 2.2 2.0 2.0 Magnesium, (mM) 0.8 0.8 0.8 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(254) TABLE-US-00030 TABLE N The result of Example N, with Qb 120 ml/min, Qpbp 13.7 ml/min, Qpre 0.0 ml/min, Qpost 7.1 ml/min, Qd 20.0 ml/min. Concentration of plasma returning Result to patient (mmol/l) Citrate, total 4.90 Phosphate, total 0.99 Calcium, total 2.14 Calcium, ionized 0.36 Bicarbonate (total CO.sub.2) 18.61 Bicarbonate + citrate 33.31 pH 7.61

Example O

(255) TABLE-US-00031 Anticoagulation Infusion fluid for Dialysis Component fluid preinfusion fluid Citrate, (mM) 30 4 4 Phosphate, (mM) 1.0 0.6 1.0 Calcium, (mM) 2.4 0 0 Magnesium, (mM) 0.5 0.5 0.5 Potassium, (mM) 3 3 3 Glucose, (mM) 0 0 5.5 Sodium, (mM) 140 140 140 Bicarbonate 0 15 15

(256) TABLE-US-00032 TABLE O The result of Example O, Qb 120 ml/min, Qpbp 16.0 ml/min, Qpre 4.8 ml/min, Qpost 0.0 ml/min, Qd 20.0 ml/min. Concentration of plasma returning to patient (mmol/l) Citrate, total 4.60 Phosphate, total 1.07 Calcium, total 1.63 Calcium, ionized 0.26 Bicarbonate (total CO.sub.2) 18.72 Bicarbonate + citrate 32.51 pH 7.66

(257) With the balanced anticoagulation fluids together with the dialysis fluids and/or infusion fluids of the present invention the possibility to vary the flow rates of the different fluids within the multipart fluid system in a large interval without causing any acid-base imbalance within the patient is also provided.

(258) While the invention has been described in connection with what is presently considered to be the most practical embodiments, it is to be understood that the invention is not to be limited to the disclosed embodiments, but on the contrary, is intended to cover various modifications and equivalents included within the spirit and the scope of the appended claims.