WO1998029151A1 - Dialysis solution, process and device for applying a dialysis treatment - Google Patents

Dialysis solution, process and device for applying a dialysis treatment Download PDF

Info

Publication number
WO1998029151A1
WO1998029151A1 PCT/EP1997/007319 EP9707319W WO9829151A1 WO 1998029151 A1 WO1998029151 A1 WO 1998029151A1 EP 9707319 W EP9707319 W EP 9707319W WO 9829151 A1 WO9829151 A1 WO 9829151A1
Authority
WO
WIPO (PCT)
Prior art keywords
dialysis
blood
dialysis solution
solution
citrate
Prior art date
Application number
PCT/EP1997/007319
Other languages
German (de)
French (fr)
Inventor
Klaus Sodemann
Original Assignee
Klaus Sodemann
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Klaus Sodemann filed Critical Klaus Sodemann
Priority to EP97954979A priority Critical patent/EP1011748A1/en
Publication of WO1998029151A1 publication Critical patent/WO1998029151A1/en

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3672—Means preventing coagulation
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/06—Aluminium, calcium or magnesium; Compounds thereof, e.g. clay
    • A61K33/10—Carbonates; Bicarbonates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/14—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis
    • A61M1/16—Dialysis systems; Artificial kidneys; Blood oxygenators ; Reciprocating systems for treatment of body fluids, e.g. single needle systems for hemofiltration or pheresis with membranes
    • A61M1/1654—Dialysates therefor
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3424—Substitution fluid path
    • A61M1/3431—Substitution fluid path upstream of the filter
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3455—Substitution fluids
    • A61M1/3458—Substitution fluids having electrolytes not present in the dialysate
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/34—Filtering material out of the blood by passing it through a membrane, i.e. hemofiltration or diafiltration
    • A61M1/342—Adding solutions to the blood, e.g. substitution solutions
    • A61M1/3455—Substitution fluids
    • A61M1/3465—Substitution fluids using dialysate as substitution fluid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M1/00—Suction or pumping devices for medical purposes; Devices for carrying-off, for treatment of, or for carrying-over, body-liquids; Drainage systems
    • A61M1/36—Other treatment of blood in a by-pass of the natural circulatory system, e.g. temperature adaptation, irradiation ; Extra-corporeal blood circuits
    • A61M1/3672—Means preventing coagulation
    • A61M1/3675—Deactivation

Definitions

  • the invention relates to a new dialysis solution for use in hemodia-filtration treatment and relates in particular to a calcium-free, citrate-containing dialysis solution which, after sterile filtration, is also used as a substitution solution, concentrates for its production and a device for its use.
  • the invention further relates to a new method using the dialysis solution.
  • anticoagulant substances used to date such as unfractionated heparin, low molecular weight heparin or also recently synthetically produced hirudin, basically have an influence on the coagulation situation of the human organism when used. Despite numerous efforts, the risk of bleeding from all of these methods has not yet been satisfactorily resolved.
  • DE-OS 41 14 908.4 describes a dialysis solution, the main advantage of which is that citrate ions are supplied to the blood from a citrate-containing dialysis solution by means of diffusion over the membrane of the filter.
  • a disadvantage of this method is that the anticoagulation does not start until the dialysis filter itself and the tube section between the blood removal needle (so-called "arterial needle") and the entry into the filter has no anticoagulation.
  • This procedure also has the disadvantage that undesirably high citrate concentrations are sometimes required for effective anticoagulation in the extracorporeal system.
  • the present invention is therefore based on the object of eliminating the disadvantages of the previous methods described above.
  • the invention relates to a dialysis solution for use in dialysis treatment with artificial kidneys, which is essentially free of calcium and magnesium and contains citrate and sodium ions, the amount of hydrogen carbonate in the solution not exceeding 32 mmol / l.
  • a method for extracorporeal treatment of a blood sample in which the dialysis solution according to the invention is added to the blood sample before the dialysis filter is reached in physiologically tolerable amounts.
  • the present invention relates to a device for carrying out the method in which the supply lines for blood and dialysis solution to the dialysis cell are connected in such a way that the dialysis solution is supplied to the blood before it reaches the dialysis cell.
  • the attached figure shows a schematic representation of the method of operation of the method according to the invention.
  • Blood is fed to the dialysis filter (2) via line (1) and, after treatment in the filter (4), returns to the starting point via line (3).
  • the current flow of the blood is regulated by a pump device (5).
  • the dialysis solution (13) according to the invention reaches the dialysis filter (2) via the supply line (6) and out of the filter again via the outgoing line (7).
  • Part of the dialysis solution is removed from the supply line (6) by means of line (8) and added to line (1) upstream of the filter unit (2).
  • the amount of dialysis solution removed can be regulated by a pump device (9).
  • Ca and Mg ions are added to the blood flowing back to the starting point via line (10), the flow rate of which can be regulated by a pump device (12).
  • the amount of citrate in the solution according to the invention is between about 1-15 mmol / 1, preferably between about 5 to 13 mmol / 1. Most preferably, the amount of citrate ions is 6 mmol / 1.
  • the amount of sodium ions is generally between 130 and 165 mmol / 1, with an amount of 133-145 mmol / 1 being preferred.
  • the most suitable amount of sodium ion has been found to be 138 mmol / l.
  • the amount of hydrogen carbonate contained in the dialysis solution according to the invention may not exceed 32 mmol according to the invention, since otherwise metabolic alkalosis can be expected.
  • the pH of the solution to be used is usually in the physiological range, a weakly acidic range in the range 4.8-7.5 having proven to be expedient. A range of 6.5-7.1 is preferred, and a pH of 6.8 is most preferred.
  • the pH of the solutions can be adjusted accordingly by the person skilled in the art on the basis of his general specialist knowledge and taking into account the respective patient data.
  • To adjust the pH it has proven to be appropriate to combine trisodium tricitrate and citric acid accordingly, so that, for example at a concentration of 5 mmol / 1 trisodium citrate, 1 mmol / 1 citric acid is added.
  • the osmolarity of the dilution used is not particularly limited, provided that it is physiologically acceptable.
  • the osmolarity is preferably in the range of approximately 260 mOsm / 1 - 330 mOsm / 1, and can be adjusted by the attending physician to the needs of the respective patient, if necessary.
  • the preferred osmolarity is between 280-300 mOsm / 1.
  • the osmolarity is preferably set by glucose, although other agents known in the art, such as amino acids, can also be used.
  • Glucose is particularly suitable because it is readily metabolically degradable and is also inexpensive. In addition, the effect on the respective patient can be determined simply by measuring blood sugar.
  • the dialysis solution according to the invention can also be in the form of a concentrate, for example to facilitate transportation, and can be diluted with an appropriate solution directly on the device if required.
  • the desired dilution, the pH value and the respective osmolarity of the feed solution can be set directly on the device by the dilution selected in each case.
  • citrate Smaller quantities of citrate can also be used. This is particularly advantageous for patients in whom citrate metabolism is disturbed due to liver disease, so that their metabolic capacity does not have to be exceeded by citrate by choosing extremely small amounts of citrate in the dialysis solution.
  • the small amounts of citrate also mean that the acid-base balance which is already disturbed in a dialysis patient is no longer adversely affected.
  • the combination of citrate with the specified small amounts of bicarbonate rather causes an advantageous buffering of the disturbed acid-base balance of the blood of a dialysis patient.
  • the solution according to the invention has also made it possible to completely dispense with the use of acetate in the dialysis solution, which had to be used in hydrogen carbonate dialysis in a concentration of 3 mmol / l.
  • the acetic acid can be replaced by citric acid, which is taken up into the patient's circulation without the problems associated with acetate, which have the disadvantageous effect on the circulation stability of the patient.
  • a portion of the citrate-containing, calcium- and magnesium-free solution with a reduced sodium hydrogen carbonate content is withdrawn from the dialysis circuit by a pump and, if necessary after sterile filtration, supplied to the blood before reaching the filter.
  • a preferred mixing ratio is achieved in that the blood flow is approximately five times higher than the flow of the citrate-containing solution supplied (at a blood flow of 250 ml / min, 50 ml / min of citrate-containing solution is therefore pumped into the blood).
  • a commercially available device from Fresenius Medical Care (MTS 4008 Mono) with some modifications can be used to carry out the method.
  • the pumps in the device are used by changing the control software so that the solutions according to the invention can be supplied by means of pumps.
  • the dialysis centers do not receive the dialysis solution, but rather concentrates that are diluted with reverse osmosis water for use on the patient in the dialysis machine.
  • 2 concentrates are used, one of which contains the cation sodium and the two anions hydrogen carbonate and trivalent citrate as soluble salts as the so-called basic concentrate.
  • the ion concentration ratio between citrate and sodium is as listed above.
  • the second concentrate (individual concentrate) optionally contains potassium chloride in a variable amount, as well as 1 mmol / 1 citric acid and optionally 2 g / 1 glucose monohydrate in order to increase the osmolarity.
  • the basic concentrate contains the essential components of the solution according to the invention and the individual concentrate enables adaptation to different operating conditions with increased / reduced potassium values of the respective patient.
  • An exemplary basic concentrate or individual concentrate contains the following components:
  • a concentration of 4 mmol / 1 citrate in the blood is generally sufficient to achieve an effective coagulation inhibition.
  • 6 mmol of the anion citrate are added to the final dialysis bath, 5 mmol / 1 deriving from trisodium citrate (basic concentrate) and 1 mmol / 1 from citric acid (individual concentrate).
  • Citric acid replaces the acetic acid typically added in bicarbonate dialysis.
  • the basic concentrate for citrate dialysis which contains sodium hydrogen carbonate and trisodium citrate, is diluted for use in the machine, preferably in a ratio of 1:15.
  • the second described individual concentrate containing glucose and citric acid is diluted in a ratio of 1: 150 for use . This dilution takes place in the machine, then the diluted concentrates are combined and represent the dialysis solution shown in claim 1.
  • the dialysis solution (13) prepared from basic and individual concentrate is pumped into the dialysis filter at a flow rate of 500 ml / min in counterflow to the blood.
  • typically 40 to 50 ml / min are branched off from the dialysis solution (13) by means of a further pump (9), which are fed to the so-called arterial blood tube after sterile filtration via a further filter (not shown).
  • the blood flow is typically 200 to 250 ml / min, so that a citrate concentration of 1.2 mmol / l in the blood flowing into the filter unit is achieved with the given setting in a ratio of approximately 5: 1.
  • the citrate content of the blood increases by diffusion from the citrate-containing dialysis solution to approximately 4 mmol / l, with which the blood ultimately leaves the filter. Due to this concentration and the lack of calcium and magnesium in the dialysis bath is in the filter and completely prevents blood clotting from the tube sections behind it.
  • a calcium / magnesium solution in the bypass is added via the lying venous needle. The flow rate for this solution is about 100 ml / hour and is caused by the pump (12). By adding calcium to the venous blood, coagulation is immediately normalized again.
  • a programmatic control can ensure that only all pumps can work at the same time, i.e. with the blood pump running, both ready-mixed dialysate must be provided and substitute solution must be pumped into the blood tube. It is also possible that calcium / magnesium chloride solution is simultaneously conveyed into the venous needle. If one pump stops, the other pumps must also be deactivated.
  • the ratio of blood flow to substitute solution flow is typically set to a predetermined value, preferably 5: 1, and the liquid balance is achieved automatically by the existing balance chamber system of the machine. With a typical treatment time of 4 to 5 hours, an additional 400 to 500 ml of ultrafiltration must be taken into account due to the calcium and magnesium chloride intake.

Landscapes

  • Health & Medical Sciences (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Anesthesiology (AREA)
  • Hematology (AREA)
  • Biomedical Technology (AREA)
  • Engineering & Computer Science (AREA)
  • Cardiology (AREA)
  • Urology & Nephrology (AREA)
  • Chemical & Material Sciences (AREA)
  • Inorganic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Emergency Medicine (AREA)
  • External Artificial Organs (AREA)

Abstract

A new Ca- and Mg-free dialysis solution contains citrate as anticoagulant and has a sodium hydrogen carbonate content which does not exceed 32 mmoles/l. During dialysis, part of the dialysis solution is added to the blood before it enters the dialysis cell. A device in which the tube coming from the patient and the tube for supplying dialysis solution to the dialysis cell are united enables implementing the process.

Description

DIALYSELÖSUNG UND VERFAHREN UND VORRICHTUNG ZUR DURCHFÜHRUNG EINER DIALYSF- BEHANDLUNG uiΛLϊitDIALYSIS SOLUTION AND METHOD AND DEVICE FOR CARRYING OUT A DIALYSF TREATMENT u iΛ Lϊ i t
Die Erfindung betrifft eine neue Dialyselösung zur Verwendung bei der Hämodia- filtrationsbehandlung und bezieht sich insbesondere auf eine calciumfreie, citrathaltige Dialyselösung, die nach Sterilfiltration auch als Substitutionslösung eingesetzt wird, Konzentrate zu deren Herstellung und eine Vorrichtung zu deren Anwendung. Die Erfindung betrifft weiterhin ein neues Verfahren unter Verwendung der Dialyselösung.The invention relates to a new dialysis solution for use in hemodia-filtration treatment and relates in particular to a calcium-free, citrate-containing dialysis solution which, after sterile filtration, is also used as a substitution solution, concentrates for its production and a device for its use. The invention further relates to a new method using the dialysis solution.
Bei der Hämodialysebehandlung stellt die Notwendigkeit der Gerinnungshemmung unverändert ein kritisches Problem dar. Die bisher eingesetzten, gerinnungshemmenden Substanzen, wie unfraktioniertes Heparin, niedermolekulares Heparin oder auch neuerdings synthetisch hergestelltes Hirudin weisen bei ihrer Anwendung grundsätzlich Einflüsse auf die Gerinnungssituation des menschlichen Organismus auf. Die Blutungsgefährdung durch all diese Verfahren ist trotz zahlreicher Anstrengungen bislang noch nicht befriedigend gelöst.In hemodialysis treatment, the need for anticoagulation continues to be a critical problem. The anticoagulant substances used to date, such as unfractionated heparin, low molecular weight heparin or also recently synthetically produced hirudin, basically have an influence on the coagulation situation of the human organism when used. Despite numerous efforts, the risk of bleeding from all of these methods has not yet been satisfactorily resolved.
Zur lokalen Gerinnungshemmung im extrakorporalen Kreislauf wird gemäß einer Veröffentlichung von Pinnick et al. (New England Journal of Medicine 2ΩS (1983), 258-263) Trinatrium-Citrat eingesetzt. Der Einsatz dieses Verfahrens ist jedoch experimentiell, da die technischen Voraussetzungen für einen routinemäßigen Einsatz bisher nicht vorhanden sind. Das Verfahren hat sich zwar dahingehend vorteilhaft erwiesen, daß keine Einflüsse auf die allgemeine Gerinnungssituation des Patienten auftreten, konnte sich aber aufgrund des Fehlens von entsprechend zubereiteten Lösungen als Routineverfahren nicht etablieren.For local anticoagulation in the extracorporeal circulation is according to a publication by Pinnick et al. (New England Journal of Medicine 2ΩS (1983), 258-263) used trisodium citrate. The use of this method is experimental, however, since the technical requirements for routine use have not yet been met. The method has proven to be advantageous in that there are no influences on the general coagulation situation of the patient, but could not establish itself as a routine method due to the lack of appropriately prepared solutions.
Die DE-OS 41 14 908.4 beschreibt eine Dialyselösung, deren wesentlicher Vorteil darin liegt, daß dem Blut mittels Diffusion über die Membran des Filters aus einer citrathaltigen Dialyselösung Citrationen zugeführt werden. Nachteilig bei diesem Verfahren ist jedoch, daß die Gerinnungshemmung erst im Dialysefilter selbst einsetzt und der Schlauchabschnitt zwischen der Entnahmenadel des Blutes (sog. "arterielle Nadel") und dem Eintritt in den Filter noch keine Gerinnungshemmung aufweist. Diese Vorgehensweise hat auch den Nachteil, daß zur wirksamen Gerinnungshemmung im extrakorporalen System teilweise unerwünscht hohe Citratkonzentrationen erforderlich sind.DE-OS 41 14 908.4 describes a dialysis solution, the main advantage of which is that citrate ions are supplied to the blood from a citrate-containing dialysis solution by means of diffusion over the membrane of the filter. A disadvantage of this method, however, is that the anticoagulation does not start until the dialysis filter itself and the tube section between the blood removal needle (so-called "arterial needle") and the entry into the filter has no anticoagulation. This procedure also has the disadvantage that undesirably high citrate concentrations are sometimes required for effective anticoagulation in the extracorporeal system.
Der vorliegenden Erfindung liegt daher die Aufgabe zugrunde, die vorstehend beschriebenen Nachteile der bisherigen Verfahren zu beheben.The present invention is therefore based on the object of eliminating the disadvantages of the previous methods described above.
Diese Aufgabe wird mit einer Dialyselösung gelöst, die einen reduzierten Gehalt an Hydrogencarbonat aufweist und dem Blut noch vor Eintritt in die Dialyse-Filtereinheit zugesetzt wird. Gemäß einer Ausführungsform betrifft die Erfindung eine Dialyselösung zur Verwendung bei der Dialysebehandlung mit künstlichen Nieren, welche im wesentlichen calcium- und magnesiumfrei ist und Citrat- sowie Natriumionen enthält, wobei die Menge an Hydrogencarbonat in der Lösung 32 mMol/1 nicht überschreitet.This object is achieved with a dialysis solution which has a reduced hydrogen carbonate content and is added to the blood before it enters the dialysis filter unit. According to one embodiment, the invention relates to a dialysis solution for use in dialysis treatment with artificial kidneys, which is essentially free of calcium and magnesium and contains citrate and sodium ions, the amount of hydrogen carbonate in the solution not exceeding 32 mmol / l.
Gemäß einer weiteren Ausführungsform wird ein Verfahren zur extrakorporalen Behandlung einer Blutprobe geliefert, bei der der Blutprobe noch vor Erreichen des Dialysefilters die erfindungsgemäße DiaJyselösung in physiologisch verträglichen Mengen zugesetzt wird.According to a further embodiment, a method for extracorporeal treatment of a blood sample is provided, in which the dialysis solution according to the invention is added to the blood sample before the dialysis filter is reached in physiologically tolerable amounts.
Gemäß noch einer weiteren Ausführungsform betrifft die vorliegende Erfindung eine Vorrichtung zur Durchführung des Verfahrens, bei dem die zuführenden Leitungen für Blut und Dialyselösung zur Dialysezelle derart verbunden sind, daß die Dialyselösung dem Blut noch vor Erreichen der Dialysezelle zugeführt wird.According to yet another embodiment, the present invention relates to a device for carrying out the method in which the supply lines for blood and dialysis solution to the dialysis cell are connected in such a way that the dialysis solution is supplied to the blood before it reaches the dialysis cell.
Die anliegende Figur zeigt eine schematische Darstellung der Arbeitsweise des erfindungsgemäßen Verfahrens. Blut wird über Leitung (1) dem Dialysefilter (2) zugeführt und gelangt nach Behandlung im Filter (4) über Leitung (3) wieder zum Ausgangsort zurück. Der Stromfluß des Blutes wird über eine Pumpenvorrichtung (5) reguliert. Die erfindungsgemäße Dialyselösung (13) gelangt über die zuführende Leitung (6) zu dem Dialysefilter (2) und durch die abgehende Leitung (7) wieder aus dem Filter heraus. Ein Teil der Dialyselösung wird mittels Leitung (8) aus der zuführenden Leitung (6) entnommen und der Leitung (1) vor der Filtereinheit (2) zugesetzt. Die Menge an abgeführter Dialyselösung kann durch eine Pumpenvorrichtung (9) reguliert werden. Über Leitung (10) werden dem zum Ausgangspunkt zurückströmenden Blut Ca- und Mg-Ionen zugesetzt, deren Strömungsmenge durch eine Pumpenvorrichtung (12) reguliert werden kann.The attached figure shows a schematic representation of the method of operation of the method according to the invention. Blood is fed to the dialysis filter (2) via line (1) and, after treatment in the filter (4), returns to the starting point via line (3). The current flow of the blood is regulated by a pump device (5). The dialysis solution (13) according to the invention reaches the dialysis filter (2) via the supply line (6) and out of the filter again via the outgoing line (7). Part of the dialysis solution is removed from the supply line (6) by means of line (8) and added to line (1) upstream of the filter unit (2). The amount of dialysis solution removed can be regulated by a pump device (9). Ca and Mg ions are added to the blood flowing back to the starting point via line (10), the flow rate of which can be regulated by a pump device (12).
Die in der erfindungsgemäßen Lösung befindliche Menge an Citrat beträgt zwischen etwa 1 - 15 mMol/1, vorzugsweise zwischen etwa 5 bis 13 mMol/1. Am meisten bevorzugt beträgt die Menge an Citrationen 6 mMol/1.The amount of citrate in the solution according to the invention is between about 1-15 mmol / 1, preferably between about 5 to 13 mmol / 1. Most preferably, the amount of citrate ions is 6 mmol / 1.
Die Menge an Natriumionen beträgt im allgemeinen zwischen 130 und 165 mMol/1, wobei eine Menge von 133-145 mMol/1 bevorzugt ist. Die Menge an Natriumionen, die sich am geeignetesten erwiesen hat, beträgt 138 mMol/1. Die in der erfindungsgemäßen Dialyselösung enthaltene Menge an Hydrogencarbonat darf erfindungsgemäß 32 mMol nicht überschreiten, da andernfalls mit einer metabolischen Alkalose zu rechnen ist.The amount of sodium ions is generally between 130 and 165 mmol / 1, with an amount of 133-145 mmol / 1 being preferred. The most suitable amount of sodium ion has been found to be 138 mmol / l. The amount of hydrogen carbonate contained in the dialysis solution according to the invention may not exceed 32 mmol according to the invention, since otherwise metabolic alkalosis can be expected.
Der pH-Wert der einzusetzenden Lösung liegt gewöhnlich im physiologischen Bereich, wobei sich ein schwach saurer Bereich im Bereich von 4,8-7,5 als zweckmäßig erwiesen hat. Bevorzugt ist ein Bereich von 6,5-7, 1, am meisten bevorzugt ist ein pH-Wert von 6,8.The pH of the solution to be used is usually in the physiological range, a weakly acidic range in the range 4.8-7.5 having proven to be expedient. A range of 6.5-7.1 is preferred, and a pH of 6.8 is most preferred.
Der pH-Wert der Lösungen kann vom Fachmann anhand seines allgemeinen Fachwissens und unter Berücksichtigung der jeweiligen Patientendaten entsprechend eingestellt werden. Zur Einstellung des pH-Wertes hat es sich zweckmäßig erwiesen Trinatriumtricitrat und Zitronensäure entsprechend zu kombinieren, so daß beispielsweise bei einer Konzentration von 5 mMol/1 Trinatriumcitrat 1 mMol/1 Zitronensäure hinzugefügt wird.The pH of the solutions can be adjusted accordingly by the person skilled in the art on the basis of his general specialist knowledge and taking into account the respective patient data. To adjust the pH, it has proven to be appropriate to combine trisodium tricitrate and citric acid accordingly, so that, for example at a concentration of 5 mmol / 1 trisodium citrate, 1 mmol / 1 citric acid is added.
Die Osmolarität der eingesetzten Verdünnung ist nicht besonders beschränkt, mit der Maßgabe, daß sie physiologisch verträglich ist. Die Osmolarität liegt vorzugsweise im Bereich von ca. 260 mOsm/1 - 330 mOsm/1, und kann vom behandelnden Arzt gegebenenfalls auf die Bedürfnisse des jeweiligen Patienten abgestimmt werden. Die bevorzugte Osmolarität liegt zwischen 280 - 300 mOsm/1. Die Osmolarität wird bevorzugt durch Glucose eingestellt, wobei jedoch auch andere im Stand der Technik bekannte Mittel, wie beispielsweise Aminosäuren, verwendet werden können. Glucose ist besonders geeignet, da sie gut metabolisch abbaubar und zudem kostengünstig ist. Darüber hinaus kann der Effekt auf den jeweiligen Patienten einfach durch Blutzuckermessungen bestimmt werden.The osmolarity of the dilution used is not particularly limited, provided that it is physiologically acceptable. The osmolarity is preferably in the range of approximately 260 mOsm / 1 - 330 mOsm / 1, and can be adjusted by the attending physician to the needs of the respective patient, if necessary. The preferred osmolarity is between 280-300 mOsm / 1. The osmolarity is preferably set by glucose, although other agents known in the art, such as amino acids, can also be used. Glucose is particularly suitable because it is readily metabolically degradable and is also inexpensive. In addition, the effect on the respective patient can be determined simply by measuring blood sugar.
Die erfindungsgemäße Dialyselösung kann zudem als Konzentrat vorliegen, um beispielsweise den Transport zu erleichtern und kann bei Bedarf direkt am Gerät mit einer entsprechenden Lösung verdünnt werden.The dialysis solution according to the invention can also be in the form of a concentrate, for example to facilitate transportation, and can be diluted with an appropriate solution directly on the device if required.
Dabei kann durch die jeweils gewählte Verdünnung die für den jeweilig zu behandelnden Patienten gewünschte Konzentration, der pH-Wert, sowie die jeweilige Osmolarität der Einsatzlösung direkt an der Vorrichtung eingestellt werden.The desired dilution, the pH value and the respective osmolarity of the feed solution can be set directly on the device by the dilution selected in each case.
Es hat sich nun gezeigt, daß der Gerinnungsneigung des Blutes durch Hämokonzentration im Filter und durch die große Oberfläche des Filters einerseits durch das Aufschwemmen des Blutes vor Erreichen der Filtereinheit und gleichzeitig durch Zufuhr von steigenden Citratmengen im Filter erfolgreich begegnet werden kann. Zusätzlich zeigt sich, daß ein verstärkter konvektiver Stofftransport im Filter stattfindet, was überraschenderweise, im Vergleich zur herkömmlichen Hämodialyse, eine verbesserte Reinigungswirkung für größere Moleküle ergibt.It has now been shown that the tendency of the blood to clot can be successfully countered by hemoconcentration in the filter and by the large surface area of the filter, on the one hand, by flushing the blood before reaching the filter unit and, at the same time, by supplying increasing amounts of citrate in the filter. In addition, it shows that an increased convective mass transfer takes place in the filter, which surprisingly, in Compared to conventional hemodialysis, an improved cleaning effect for larger molecules results.
Dabei sind auch geringere Citratmengen verwendbar. Dies ist insbesondere bei Patienten von Vorteil, bei denen aufgrund einer Lebererkrankung der Citrat-Stoffwechsel gestört ist, so daß deren Verstoffwechselkapazität von Citrat durch Wahl äußerst geringer Citratmengen in der Dialyselösung nicht überschritten werden muß.Smaller quantities of citrate can also be used. This is particularly advantageous for patients in whom citrate metabolism is disturbed due to liver disease, so that their metabolic capacity does not have to be exceeded by citrate by choosing extremely small amounts of citrate in the dialysis solution.
Die geringen Citratmengen führen auch dazu, daß der bei einem Dialysepatienten bereits gestörte Säure-Base-Haushalt nicht weiter nachteilig beeinflußt wird. Durch die Kombination von Citrat mit den angegebenen geringen Mengen an Hydrogencarbonat wird vielmehr eine vorteilhafte Abpufferung des gestörten Säure-Base-Gleichgewichts des Blutes eines Dialysepatienten bewirkt.The small amounts of citrate also mean that the acid-base balance which is already disturbed in a dialysis patient is no longer adversely affected. The combination of citrate with the specified small amounts of bicarbonate rather causes an advantageous buffering of the disturbed acid-base balance of the blood of a dialysis patient.
Durch die erfindungsgemäße Lösung ist es darüber hinaus auch möglich geworden, in der Dialyselösung vollständig auf die Verwendung von Acetat zu verzichten, das bei der Hydrogencarbonat-Dialyse in einer Konzentration von 3 mMol/1 eingesetzt werden mußte. Die Essigsäure kann in dem erfmdungsgemäßen Verfahren durch Citronensäure ersetzt werden, die in den Kreislauf des Patienten ohne die mit Acetat einhergehenden Probleme der nachteiligen Auswirkung auf die Kreislaufstabilität des Patienten aufgenommen wird.The solution according to the invention has also made it possible to completely dispense with the use of acetate in the dialysis solution, which had to be used in hydrogen carbonate dialysis in a concentration of 3 mmol / l. In the method according to the invention, the acetic acid can be replaced by citric acid, which is taken up into the patient's circulation without the problems associated with acetate, which have the disadvantageous effect on the circulation stability of the patient.
Als Filter für die Dialyse sind alle im Stand der Technik bekannten Filter einsetzbar und der für den jeweiligen Einsatz zweckmäßigste Filter kann unter Berücksichtigung der jeweiligen Patientendaten gewählt werden.All filters known in the prior art can be used as filters for dialysis, and the filter that is most appropriate for the particular application can be selected taking into account the respective patient data.
Die Erfindung wird nun im folgenden näher erläutert.The invention will now be explained in more detail below.
Ein Teil der citrathaltigen, calcium- und magnesiumfreien Lösung mit reduziertem Natriumhydrogencarbonatgehalt wird dem Dialysekreislauf durch eine Pumpe entzogen und gegebenenfalls nach Sterilfiltration dem Blut noch vor Erreichen des Filters zugeführt. Ein bevorzugtes Mischungsverhältnis wird dadurch erzielt, daß der Blutfluß ca. fünfmal höher liegt als der Fluß der zugeführten citrathaltigen Lösung (bei einem Blutfluß von 250 ml/min werden folglich 50 ml/min citrathaltige Lösung ins Blut gepumpt). Zur Durchführung des Verfahrens kann ein im Handel erhältliches Gerät der Firma Fresenius Medical Care (MTS 4008 Mono) mit einigen Modifikationen eingesetzt werden. Die in dem Gerät vorhandenen Pumpen werden durch eine Änderung der Steuerungssoftware so eingesetzt, daß die erfindungsgemäßen Lösungen mittels Pumpen zugeführt werden können. Nach dem aktuellen Stand der Dialysetechnik handelt es sich definitionsgemäß um eine Hämodiafiltration mit On-line-Herstellung einer sterilen, calcium- und magnesiumfreien, citrathaltigen Dialyselösung, die als Substitutionslösung in Prädilutionstechnik eingesetzt wird. Wegen der calcium- und magnesiumfreien Dialyselösung muß zur Erzielung einer ausgeglichenen Salzbilanz über eine Pumpe ein Calcium- und Magnesiumchlorid-Gemisch unmittelbar über die zum Patienten zurückführende Anschlußnadel gegeben werden. Eine grundsätzliche Beschreibung des Verfahrens findet sich in der DE-OS 41 14 908, die hiermit unter Bezugnahme mit aufgenommen wird.A portion of the citrate-containing, calcium- and magnesium-free solution with a reduced sodium hydrogen carbonate content is withdrawn from the dialysis circuit by a pump and, if necessary after sterile filtration, supplied to the blood before reaching the filter. A preferred mixing ratio is achieved in that the blood flow is approximately five times higher than the flow of the citrate-containing solution supplied (at a blood flow of 250 ml / min, 50 ml / min of citrate-containing solution is therefore pumped into the blood). A commercially available device from Fresenius Medical Care (MTS 4008 Mono) with some modifications can be used to carry out the method. The pumps in the device are used by changing the control software so that the solutions according to the invention can be supplied by means of pumps. According to the current state of dialysis technology, hemodiafiltration with on-line production of a sterile, calcium- and magnesium-free, citrate-containing dialysis solution is used, which is used as a substitution solution in predilution technology. Because of the calcium- and magnesium-free dialysis solution, a calcium and magnesium chloride mixture must be given directly over the connecting needle leading back to the patient in order to achieve a balanced salt balance. A basic description of the method can be found in DE-OS 41 14 908, which is hereby incorporated by reference.
In der erfindungsgemäßen Dialyselösung liegt das Verhältnis der Citrationenkonzentration und der Natriumionenkonzentration vorzugsweise zwischen 1 : 160 und 1 : 9 (= 15 : 130).In the dialysis solution according to the invention, the ratio of the citrate ion concentration and the sodium ion concentration is preferably between 1: 160 and 1: 9 (= 15: 130).
Üblicherweise wird den Dialysezentren nicht die Dialyselösung angeliefert, sondern Konzentrate, die für die Anwendung am Patienten in der Dialysemaschine mit Umkehrosmosewasser verdünnt werden. Gemäß einer bevorzugten Ausführungsform der Erfindung werden 2 Konzentrate eingesetzt, wobei das eine als sogenanntes Grundkonzentrat das Kation Natrium und die beiden Anionen Hydrogencarbonat und dreiwertiges Citrat als lösliche Salze enthalten. Das Ionenkonzentrationsverhältnis zwischen Citrat und Natrium liegt hierbei wie vorstehend aufgeführt. Das zweite Konzentrat (Individualkonzentrat) enthält neben Natriumchlorid gegebenenfalls Kaliumchlorid in einer variablen Menge, sowie 1 mMol/1 Zitronensäure und gegebenenfalls 2 g/1 Glucosemonohydrat, um die Osmolarität anzuheben.Usually, the dialysis centers do not receive the dialysis solution, but rather concentrates that are diluted with reverse osmosis water for use on the patient in the dialysis machine. According to a preferred embodiment of the invention, 2 concentrates are used, one of which contains the cation sodium and the two anions hydrogen carbonate and trivalent citrate as soluble salts as the so-called basic concentrate. The ion concentration ratio between citrate and sodium is as listed above. In addition to sodium chloride, the second concentrate (individual concentrate) optionally contains potassium chloride in a variable amount, as well as 1 mmol / 1 citric acid and optionally 2 g / 1 glucose monohydrate in order to increase the osmolarity.
Das Grundkonzentrat enthält die wesentlichen Komponenten der erfindungsgemäßen Lösung und das Individualkonzentrat ermöglicht die Anpassung an unterschiedliche Einsatzbedingungen bei erhöhten/erniedrigten Kaliumwerten des jeweiligen Patienten.The basic concentrate contains the essential components of the solution according to the invention and the individual concentrate enables adaptation to different operating conditions with increased / reduced potassium values of the respective patient.
Ein bespielhaft aufgeführtes Grundkonzentrat bzw. Individualkonzentrat enthält die folgenden Bestandteile:An exemplary basic concentrate or individual concentrate contains the following components:
Grundkonzentrat:Basic concentrate:
Natriumhydrogencarbonat 28,04 g, Tri-Natriumcitrat x 2 H2O 23, 16 gSodium hydrogen carbonate 28.04 g, trisodium citrate x 2 H 2 O 23, 16 g
Natriumchlorid 74, 51 gSodium chloride 74.51 g
Wasser 956 ml. Individualkonzentrat:Water 956 ml. Individual concentrate:
Natriumchlorid 131 ,49 g Kaliumchlorid 22,37 g Citronensäure Monohydrat 23,64 g Glucose Monohydrat 330,0 gSodium chloride 131, 49 g potassium chloride 22.37 g citric acid monohydrate 23.64 g glucose monohydrate 330.0 g
Aqua ad inj . 708 mlAqua ad inj. 708 ml
pH-Wert der Verdünnung (1 + 149) 3,35 Osmolarität der Verdünnung (1 + 149) 45,85 mOsmol/1Dilution pH (1 + 149) 3.35 Dilution osmolarity (1 + 149) 45.85 mOsmol / 1
Bei Einsatz einer calcium- und magnesiumfreien Dialyselösung ist eine Konzentration von 4 mMol/1 Citrat im Blut im allgemeinen ausreichend, um eine effektive Gerinnungs- hemmung zu erzielen. Aus diesem Grund werden dem endgültigen Dialysebad, 6 mMol des Anions Citrat zugesetzt, wobei 5 mMol/1 aus Trinatrium-Citrat herrühren (Grundkonzentrat) und 1 mMol/1 aus Zitronensäure (Individualkonzentrat). Die Zitronensäure ersetzt die typischerweise bei der Bicarbonatdialyse hinzugefügte Essigsäure.When using a calcium- and magnesium-free dialysis solution, a concentration of 4 mmol / 1 citrate in the blood is generally sufficient to achieve an effective coagulation inhibition. For this reason, 6 mmol of the anion citrate are added to the final dialysis bath, 5 mmol / 1 deriving from trisodium citrate (basic concentrate) and 1 mmol / 1 from citric acid (individual concentrate). Citric acid replaces the acetic acid typically added in bicarbonate dialysis.
Das Grundkonzentrat für die Citratdialyse, das Natriumhydrogencarbonat und Trinatrium- Citrat enthält, wird für die Anwendung in der Maschine verdünnt, vorzugsweise im Ver- hältnis 1: 15. Das zweite beschriebene glucose- und zitronensäurehaltige Individualkonzentrat wird für die Anwendung im Verhältnis 1: 150 verdünnt. Diese Verdünnung geschieht in der Maschine, anschließend werden die verdünnten Konzentrate zusammengeführt und stellen die in Anspruch 1 dargestellte Dialyselösung dar.The basic concentrate for citrate dialysis, which contains sodium hydrogen carbonate and trisodium citrate, is diluted for use in the machine, preferably in a ratio of 1:15. The second described individual concentrate containing glucose and citric acid is diluted in a ratio of 1: 150 for use . This dilution takes place in the machine, then the diluted concentrates are combined and represent the dialysis solution shown in claim 1.
Die Wirkungsweise des erfindungsgemäßen Verfahrens wird nun unter Bezugnahme auf die Zeichnung näher erläutert.The mode of operation of the method according to the invention will now be explained in more detail with reference to the drawing.
Die aus Grund- und Individualkonzentrat hergestellte Dialyselösung (13) wird mit einer Flußgeschwindigkeit von 500 ml/min im Gegenstrom zum Blut in den Dialysefilter gepumpt. Vor Erreichen des Dialysefilters werden aus der Dialyselösung (13) mittels einer weiteren Pumpe (9) typischerweise 40 bis 50 ml/min abgezweigt, die nach einer Sterilfiltration über einen weiteren Filter (nicht gezeigt) dem sogenannten arteriellen Blutschlauch zugeführt werden. Der Blutfluß beträgt typischerweise 200 bis 250 ml/min, so daß bei der vorgegebenen Einstellung im Verhältnis von ca. 5: 1 eine Citratkon- zentration von 1,2 mMol/1 im in die Filtereinheit einströmenden Blut erreicht wird. Im weiteren Verlauf steigt der Citratgehalt des Blutes durch Diffusion aus der citrathaltigen Dialyselösung auf ca. 4 mMol/1 an, mit der das Blut letztlich den Filter verläßt. Durch diese Konzentration und fehlendes Calcium und Magnesium im Dialysebad wird im Filter und den dahinterliegenden Schlauchabschnitten eine Blutgerinnung vollständig verhindert. Zum Ausgleich des Calcium- und Magnesiumverlustes im Dialysefilter wird eine Calcium- /Magnesiumlösung im Bypass über die liege ide venöse Nadel zugegeben. Die Strömungsgeschwindigkeit für diese Lösung liegt bei etwa 100 ml/Std und wird durch die Pumpe (12) bewirkt. Durch die Calciumzugabe ins venöse Blut wird die Gerinnung unmittelbar wieder normalisiert.The dialysis solution (13) prepared from basic and individual concentrate is pumped into the dialysis filter at a flow rate of 500 ml / min in counterflow to the blood. Before reaching the dialysis filter, typically 40 to 50 ml / min are branched off from the dialysis solution (13) by means of a further pump (9), which are fed to the so-called arterial blood tube after sterile filtration via a further filter (not shown). The blood flow is typically 200 to 250 ml / min, so that a citrate concentration of 1.2 mmol / l in the blood flowing into the filter unit is achieved with the given setting in a ratio of approximately 5: 1. In the further course, the citrate content of the blood increases by diffusion from the citrate-containing dialysis solution to approximately 4 mmol / l, with which the blood ultimately leaves the filter. Due to this concentration and the lack of calcium and magnesium in the dialysis bath is in the filter and completely prevents blood clotting from the tube sections behind it. To compensate for the loss of calcium and magnesium in the dialysis filter, a calcium / magnesium solution in the bypass is added via the lying venous needle. The flow rate for this solution is about 100 ml / hour and is caused by the pump (12). By adding calcium to the venous blood, coagulation is immediately normalized again.
Durch eine programmtechnische Steuerung kann erreicht werden, daß nur alle Pumpen gleichzeitig arbeiten können, d.h. bei laufender Blutpumpe muß sowohl fertiggemischtes Dialysat bereitgestellt als auch Substitutionslösung in den Blutschlauch gepumpt werden. Zudem ist es möglich, daß gleichzeitig Calcium-/Magnesiumchlorid-Lösung in die venöse Nadel gefördert wird. Bei Stillstand einer Pumpe müssen auch die übrigen Pumpen inaktiviert werden. Das Verhältnis von Blutfluß zu Substitutionslösungsfluß ist typischerweise auf einen vorbestimmten Wert, vorzugsweise 5 : 1, fix eingestellt, und die Flüssig- keitsbilanzierung wird durch das vorhandene Bilanzkammersystem der Maschine automatisch erreicht. Bei einer typischen Behandlungsdauer von 4 bis 5 Stunden müssen noch zusätzliche 400 bis 500 ml Ultrafiltration wegen der Calcium- und Magnesiumchloridzufuhr berücksichtigt werden. A programmatic control can ensure that only all pumps can work at the same time, i.e. with the blood pump running, both ready-mixed dialysate must be provided and substitute solution must be pumped into the blood tube. It is also possible that calcium / magnesium chloride solution is simultaneously conveyed into the venous needle. If one pump stops, the other pumps must also be deactivated. The ratio of blood flow to substitute solution flow is typically set to a predetermined value, preferably 5: 1, and the liquid balance is achieved automatically by the existing balance chamber system of the machine. With a typical treatment time of 4 to 5 hours, an additional 400 to 500 ml of ultrafiltration must be taken into account due to the calcium and magnesium chloride intake.

Claims

Patentansprüche claims
1. Dialyselösung zur Dialysebehandlung mit künstlichen Nieren, welche im wesentlichen Calcium- und Magnesiumfrei ist und zwischen etwa 1 - 15 mMol/1 Citrat sowie 130 - 165 mMol/1 Natriumionen enthält, dadurch gekennzeichnet, daß die Menge an Hydrogencarbonat 0 - 32 mMol/1 beträgt.1. Dialysis solution for dialysis treatment with artificial kidneys, which is essentially free of calcium and magnesium and contains between about 1 - 15 mmol / 1 citrate and 130 - 165 mmol / 1 sodium ions, characterized in that the amount of hydrogen carbonate is 0 - 32 mmol / 1 is.
2. Dialyselösung nach Anspruch 1 , dadurch gekennzeichnet, daß die Dialyselösung höchstens maximal etwa 0,2 mMol/1 Calcium enthält.2. Dialysis solution according to claim 1, characterized in that the dialysis solution contains a maximum of about 0.2 mmol / 1 calcium.
3. Dialyselösung nach Anspruch 1 oder 2, dadurch gekennzeichnet, daß die Dialyselösung etwa 6 mMol/1 Citrat enthält.3. Dialysis solution according to claim 1 or 2, characterized in that the dialysis solution contains about 6 mmol / 1 citrate.
4. Dialyselösung nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß die Menge an Hydrogencarbonationen 20 nιMol/1 beträgt.4. Dialysis solution according to one of the preceding claims, characterized in that the amount of hydrogen carbonate ions is 20 nmol / 1.
5. Konzentrat zur Herstellung einer Dialyselösung nach einem der vorhergehenden Ansprüche, dadurch gekennzeichnet, daß das Verhältnis des Citrat-Anteils zum Natrium- anteil zwischen etwa 1 : 160 und 1 : 9 beträgt.5. Concentrate for the production of a dialysis solution according to one of the preceding claims, characterized in that the ratio of the citrate portion to the sodium portion is between about 1: 160 and 1: 9.
6. Verfahren zur extrakorporalen Reinigung von Blut, dadurch gekennzeichnet, daß eine Dialyselösung nach einem der vorhergehenden Ansprüche dem Blut noch vor Erreichen der Dialysemembran zugesetzt wird.6. A method for extracorporeal purification of blood, characterized in that a dialysis solution according to one of the preceding claims is added to the blood before reaching the dialysis membrane.
7. Verfahren nach Anspruch 7, dadurch gekennzeichnet, daß die Menge der dem Blut zugeführten Dialyselösung 20-100 ml Dialyselösung/200 ml Blut/min beträgt.7. The method according to claim 7, characterized in that the amount of the dialysis solution supplied to the blood is 20-100 ml of dialysis solution / 200 ml of blood / min.
8. Verfahren nach Anspruch 8, dadurch gekennzeichnet, daß die Menge der dem Blut zugeführten Dialyselösung 40 ml Dialyselösung/200 ml Blut/min beträgt.8. The method according to claim 8, characterized in that the amount of the dialysis solution supplied to the blood is 40 ml dialysis solution / 200 ml blood / min.
9. Vorrichtung zur Dialysebehandlung mit künstlichen Nieren mit einer Dialysezelle, einer Förderpumpe für das Patientenblut und mit einer Förderpumpe für die Dialyselösung, zuführenden Leitungen für Blut und Dialyselösung zur Dialysezelle und abführen- den Leitungen für Blut und Dialyselösung von der Dialyselösung, dadurch gekennzeichnet, daß die zuführenden Leitungen für Blut und Dialyselösung zur Dialysezelle derart verbunden sind, daß die Dialyselösung dem Blut noch vor Erreichen der Dialysezelle zugeführt wird. 9. Device for dialysis treatment with artificial kidneys with a dialysis cell, a delivery pump for the patient's blood and with a delivery pump for the dialysis solution, supply lines for blood and dialysis solution to the dialysis cell and discharge lines for blood and dialysis solution from the dialysis solution, characterized in that the supply lines for blood and dialysis solution are connected to the dialysis cell in such a way that the dialysis solution is supplied to the blood before it reaches the dialysis cell.
10. Vorrichtung nach Anspruch 9, dadurch gekennzeichnet, daß an der Leitung zur Blutrückführung nach der Dialysezelle eine Dosierpumpe angeordnet ist, die dem Patientenblut aus einem Vorratsbehälter Ca- und Mg-Ionen zuführt.10. The device according to claim 9, characterized in that a metering pump is arranged on the line for blood return after the dialysis cell, which feeds the patient's blood from a reservoir Ca and Mg ions.
11. Vorrichtung nach einem der Ansprüche 9 und 10, dadurch gekennzeichnet, daß die zuführenden oder abführenden Leitungen der Dialysezelle Förder- oder Dosierpumpen aufweisen, die so miteinander verbunden sind, daß sie nur gleichzeitig arbeiten können.11. The device according to one of claims 9 and 10, characterized in that the supply or discharge lines of the dialysis cell have feed or metering pumps which are connected to one another so that they can only work simultaneously.
12. Vorrichtung nach einem der Ansprüche 9 bis 11 , die zusätzliche einen Stillstandsalarmgeber enthält.12. The device according to one of claims 9 to 11, which additionally contains a standstill alarm.
ERSATZBLÄTT (REGEL 26) SPARE BLADE (RULE 26)
PCT/EP1997/007319 1996-12-30 1997-12-30 Dialysis solution, process and device for applying a dialysis treatment WO1998029151A1 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP97954979A EP1011748A1 (en) 1996-12-30 1997-12-30 Dialysis solution, process and device for applying a dialysis treatment

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DE19654746.6 1996-12-30
DE19654746A DE19654746C2 (en) 1996-12-30 1996-12-30 Dialysis solution

Publications (1)

Publication Number Publication Date
WO1998029151A1 true WO1998029151A1 (en) 1998-07-09

Family

ID=7816420

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP1997/007319 WO1998029151A1 (en) 1996-12-30 1997-12-30 Dialysis solution, process and device for applying a dialysis treatment

Country Status (3)

Country Link
EP (1) EP1011748A1 (en)
DE (1) DE19654746C2 (en)
WO (1) WO1998029151A1 (en)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2002248165A (en) * 2000-12-22 2002-09-03 Fresenius Medical Care Deutschland Gmbh Method for measuring concentration and dialysis device
US6743191B1 (en) 1999-04-26 2004-06-01 Edwards Lifesciences Ag Substitution infusion fluid and citrate anticoagulation
GB2417420A (en) * 2004-08-19 2006-03-01 Aksys Ltd Citrate-based dialysate formulations
EP1721606A2 (en) 1998-10-20 2006-11-15 Advanced Renal Technologies Buffered compositions for dialysis
WO2006130065A1 (en) 2005-05-30 2006-12-07 Gambro Lundia Ab Peritoneal dialysis fluid
US7186420B2 (en) 1999-04-26 2007-03-06 Edwards Lifesciences Corporation Multi-part substitution infusion fluids and matching anticoagulants
JP2009516575A (en) * 2005-11-22 2009-04-23 エドワーズ ライフサイエンシーズ コーポレイション Citrate anticoagulation system for extracorporeal blood treatment
US7670491B2 (en) 1998-10-20 2010-03-02 Advanced Renal Technologies Buffered compositions for dialysis
US7862530B2 (en) 1999-09-22 2011-01-04 Advanced Renal Technologies High citrate dialysate and uses thereof

Families Citing this family (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19748290B8 (en) 1997-10-31 2009-09-03 Fresenius Medical Care Deutschland Gmbh Solution for peritoneal dialysis
DE19912850B4 (en) 1999-03-22 2005-04-07 Fresenius Medical Care Deutschland Gmbh Solution, in particular for hemodialysis or peritoneal dialysis, and process for its preparation
FR2800618B1 (en) * 1999-11-08 2002-02-22 Bert Christophe HEMO-FILTRATION APPARATUS FOR INDEPENDENTLY CONTROLLING THE CONCENTRATION OF AT LEAST TWO IONIC SUBSTANCES IN THE INTERIOR OF A PATIENT
US6635026B1 (en) 1999-11-08 2003-10-21 Hospal Industrie Haemofiltration machine for independently controlling the concentration of a least two ionic substances in a patient's internal medium
IT1320024B1 (en) * 2000-04-07 2003-11-12 Gambro Dasco Spa METHOD FOR ADJUSTING THE INFUSION IN A DIALYSIS MACHINE AND DIALYSIS MACHINE FOR THE APPLICATION OF THE MENTIONED METHOD.
US7935070B2 (en) 2005-01-28 2011-05-03 Fresenius Medical Care North America Systems and methods for dextrose containing peritoneal dialysis (PD) solutions with neutral pH and reduced glucose degradation product
US8845571B2 (en) * 2009-06-17 2014-09-30 Fresenius Medical Care Holdings, Inc. Methods of regional citrate anticoagulation dialysis
US9585810B2 (en) 2010-10-14 2017-03-07 Fresenius Medical Care Holdings, Inc. Systems and methods for delivery of peritoneal dialysis (PD) solutions with integrated inter-chamber diffuser
LT2826476T (en) * 2013-07-16 2021-04-12 G.M.T. De Jong B.V. Calcium-free dialysis fluid
EP3015124B1 (en) 2014-10-31 2017-08-16 B. Braun Avitum AG System for flexible citrate anticoagulation during extracorporeal blood treatment using feed-forward control

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4500309A (en) * 1982-05-07 1985-02-19 The Kansas University Endowment Association Method for regional anticoagulation during extracorporeal dialysis
WO1991006326A1 (en) * 1989-10-31 1991-05-16 The Regents Of The University Of California Continuous hemodialysis using citrate
DE4114908A1 (en) * 1991-05-07 1992-11-12 Klaus Dr Med Sodemann Dialysis soln. for use with artificial kidneys - contains low calcium ion content, but high citrate content to inhibit coagulation of blood
US5366630A (en) * 1991-08-14 1994-11-22 Hospal Industrie Artificial kidney and a method of controlling it

Family Cites Families (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE4125819A1 (en) * 1991-08-03 1993-02-04 Rolf Prof Dr Med Zander AQUEOUS SOLUTION AND THEIR USE

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4500309A (en) * 1982-05-07 1985-02-19 The Kansas University Endowment Association Method for regional anticoagulation during extracorporeal dialysis
WO1991006326A1 (en) * 1989-10-31 1991-05-16 The Regents Of The University Of California Continuous hemodialysis using citrate
DE4114908A1 (en) * 1991-05-07 1992-11-12 Klaus Dr Med Sodemann Dialysis soln. for use with artificial kidneys - contains low calcium ion content, but high citrate content to inhibit coagulation of blood
US5366630A (en) * 1991-08-14 1994-11-22 Hospal Industrie Artificial kidney and a method of controlling it

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9216247B2 (en) 1998-10-20 2015-12-22 Advanced Renal Technologies Buffered compositions for dialysis
EP1721606B1 (en) * 1998-10-20 2013-09-11 Advanced Renal Technologies Buffered compositions for dialysis
US7670491B2 (en) 1998-10-20 2010-03-02 Advanced Renal Technologies Buffered compositions for dialysis
EP1721606A2 (en) 1998-10-20 2006-11-15 Advanced Renal Technologies Buffered compositions for dialysis
EP2452685A1 (en) * 1998-10-20 2012-05-16 Advanced Renal Technologies Buffered compositions for dialysis
US7186420B2 (en) 1999-04-26 2007-03-06 Edwards Lifesciences Corporation Multi-part substitution infusion fluids and matching anticoagulants
US6743191B1 (en) 1999-04-26 2004-06-01 Edwards Lifesciences Ag Substitution infusion fluid and citrate anticoagulation
US7758900B2 (en) 1999-04-26 2010-07-20 Baxter International Inc. Multi-part substitution infusion fluids and matching anticoagulants
US8105258B2 (en) 1999-04-26 2012-01-31 Baxter International Inc. Citrate anticoagulation system for extracorporeal blood treatments
US8864699B2 (en) 1999-09-22 2014-10-21 Advanced Renal Technologies High citrate dialysate and uses thereof
US7862530B2 (en) 1999-09-22 2011-01-04 Advanced Renal Technologies High citrate dialysate and uses thereof
JP2002248165A (en) * 2000-12-22 2002-09-03 Fresenius Medical Care Deutschland Gmbh Method for measuring concentration and dialysis device
JP4558249B2 (en) * 2000-12-22 2010-10-06 フレゼニウス メディカル ケアー ドイチュラント ゲゼルシャフト ミット ベシュレンクテル ハフツング Dialysis device and method of operating the same
GB2417420A (en) * 2004-08-19 2006-03-01 Aksys Ltd Citrate-based dialysate formulations
WO2006130065A1 (en) 2005-05-30 2006-12-07 Gambro Lundia Ab Peritoneal dialysis fluid
US8367731B2 (en) 2005-05-30 2013-02-05 Fresenius Medical Care Deutschland Gmbh Peritoneal dialysis fluid
EP1890686A4 (en) * 2005-05-30 2009-11-11 Gambro Lundia Ab Peritoneal dialysis fluid
EP1890686A1 (en) * 2005-05-30 2008-02-27 Gambro Lundia AB Peritoneal dialysis fluid
JP2009516575A (en) * 2005-11-22 2009-04-23 エドワーズ ライフサイエンシーズ コーポレイション Citrate anticoagulation system for extracorporeal blood treatment

Also Published As

Publication number Publication date
EP1011748A1 (en) 2000-06-28
DE19654746C2 (en) 2000-05-11
DE19654746A1 (en) 1998-07-02

Similar Documents

Publication Publication Date Title
DE19654746C2 (en) Dialysis solution
DE4230513C1 (en) Device for removing aluminum ions from blood and solution for use in the device
DE69929555T2 (en) Use of a liquid for the preparation of a dialysis solution for continuous recirculating peritoneal dialysis
DE69834589T2 (en) Method for controlling the sodium concentration of a dialysate according to regulation
DE60027266T3 (en) Device for processing a medical fluid
DE69938035T2 (en) SAFETY DEVICE FOR DIALYSIS MACHINES AND METHOD FOR ACTIVATING THE SAFETY DEVICE
DE10339342B3 (en) Blood treatment system comprises an analysis unit which provides a control unit with information allowing blood treatment to be carried out with process parameters maintained within set value ranges
DE69834034T2 (en) DEVICE FOR CALCULATING DIALYSIS EFFICIENCY
DE60031966T2 (en) EXTRACORPORAL CIRCULATION
DE60037408T3 (en) Device for hemodialysis
EP1615680B1 (en) Haemodialysis device
DE69208785T2 (en) Artificial kidney
EP2023972B1 (en) Device and method for controlling an extracorporeal blood treatment device
DE69027052T2 (en) DIALYSAT PRODUCTION SYSTEM WITH PILLS
DE69733657T2 (en) SYSTEM FOR AVOIDING INTRADIALTIC SYMPTOMATOLOGY
DE60225596T2 (en) Device and associated software to determine blood flow during dialysis
DE60127657T2 (en) Blood purification system
EP2249898A1 (en) Method for determining the percentage of recirculation in a fistula and/or cardiopulmonary recirculation relative to the total fistula recirculation and cardiopulmonary recirculation
DE60037233T2 (en) hemofiltration
DE60025698T2 (en) NEW DIALYSIS METHOD
WO2000002604A1 (en) Method for determining dialysance and device for carrying out the method
WO2004057279A1 (en) Method and device for determining the blood flow in a blood-conducting tube
DE19854338B4 (en) Method and device for renal replacement therapy
DE4114908A1 (en) Dialysis soln. for use with artificial kidneys - contains low calcium ion content, but high citrate content to inhibit coagulation of blood
DE10245619B4 (en) Method for returning blood from a blood treatment device and device for carrying out the method

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): CA JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE DK ES FI FR GB GR IE IT LU MC NL PT SE

121 Ep: the epo has been informed by wipo that ep was designated in this application
WWE Wipo information: entry into national phase

Ref document number: 1997954979

Country of ref document: EP

WWP Wipo information: published in national office

Ref document number: 1997954979

Country of ref document: EP

WWW Wipo information: withdrawn in national office

Ref document number: 1997954979

Country of ref document: EP