WO2010055963A1 - Procédé de fabrication d'une composition de dialysat exempt d'acétate - Google Patents

Procédé de fabrication d'une composition de dialysat exempt d'acétate Download PDF

Info

Publication number
WO2010055963A1
WO2010055963A1 PCT/KR2008/006741 KR2008006741W WO2010055963A1 WO 2010055963 A1 WO2010055963 A1 WO 2010055963A1 KR 2008006741 W KR2008006741 W KR 2008006741W WO 2010055963 A1 WO2010055963 A1 WO 2010055963A1
Authority
WO
WIPO (PCT)
Prior art keywords
dialysate
acid
citric acid
chloride
acetate
Prior art date
Application number
PCT/KR2008/006741
Other languages
English (en)
Inventor
Jin Sik Lee
Jong Bok Kim
Chan Ho Jeong
Original Assignee
Lee, Jin Tae
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 Lee, Jin Tae filed Critical Lee, Jin Tae
Priority to PCT/KR2008/006741 priority Critical patent/WO2010055963A1/fr
Publication of WO2010055963A1 publication Critical patent/WO2010055963A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
    • A61K31/19—Carboxylic acids, e.g. valproic acid
    • A61K31/194—Carboxylic acids, e.g. valproic acid having two or more carboxyl groups, e.g. succinic, maleic or phthalic acid
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms
    • 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
    • A61K33/14—Alkali metal chlorides; Alkaline earth metal chlorides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/08—Solutions

Definitions

  • the present invention relates to a dialysate, a method for preparing the same and a use thereof, more particularly to preparation of an anticoagulant dialysate containing bicarbonate.
  • the dialysate used in dialysis usually contains sodium bicarbonate as a major buffering component. It is to prevent metabolic acidosis during dialysis, which may be caused by the decreased bicarbonate concentration in the blood.
  • the metabolic acidosis is known to negatively affect the bone metabolism.
  • sodium bicarbonate is provided in powder form or in highly concentrated aqueous solution as an alkalizing agent. It is provided as a dialysate for dialysis after being admixed with an acidifying agent or purified water to have an acidity of pH 7.25 ⁇ 7.45, similar to that of the human blood plasma.
  • the acidifying agent is provided as alkali metal or alkaline earth metal salt and a buffering acid dissolved in purified water at high concentration.
  • Acetic acid is the most widely used as the buffering acid, because it can effectively prevent the instability of the dialysate caused by the precipitation of divalent cations such as calcium and magnesium as carbonates.
  • a dialysate manufacturing system using an acidifying agent containing acetic acid is highly advantageous in easiness of handling during dialysis and stability of the prepared dialysate.
  • dialysates are mainly bicarbonate-based dialysates containing about 800 mEq/L of acetic acid.
  • the dialysate containing acetic acid may be associated with adverse effects caused by the acetate, which normally hardly exists in the body.
  • acetate may result in cardiovascular instability by inhibiting the action of nitrogen monoxide and blood pressure decrease during dialysis through the peripheral vasodilation.
  • the extracorporeal circuit is washed with heparin-containing saline before carrying out dialysis, and then the extracorporeal circuit is filled with the patient's blood or heparin-free saline to wash off the heparin-containing saline. Then, dialysis is carried out at the fastest speed that the patient can endure in order to minimize the risk of the dialysis disequilibrium syndrome.
  • Another practice of dialysis using a heparin-free dialysate is to reduce the calcium ion level in the blood flowing in the extracorporeal circuit to prevent blood coagulation.
  • An example of the method of decreasing the ionized calcium ion concentration of the blood in the extracorporeal circuit is to carrying out dialysis using a calcium-free dialysate while injecting sodium citrate into the arterial circuit.
  • this method may be problematic since the blood with very low calcium ion level flows back into the patient. As a result, calcium chloride has to be injected to the venous circuit to prevent hypocalcemia.
  • Dialysis is primarily used to remove waste products and water resulting from metabolism from the blood when the kidneys are in renal failure.
  • a patient who receives dialysis 3 times a week experiences 1 to 3 kg increase of body weight in between dialyses due to accumulation of water.
  • dialysis usually takes 3 to 4 hours, the patients with excessive free water need to have the water removed more quickly.
  • a low-sodium dialysate may result in osmotic imbalance. Accordingly, control of body weight in between dialyses, use of bicarbonate dialysate, control of dialysate temperature, or the like are attempted to prevent hypotension that may occur during hemodialysis.
  • alkaline sodium bicarbonate in a dialysate sodium acetate or acetic acid has been used. Development of a completely acetate-free dialysate has been restricted with regard to stability of the dialysate.
  • a bicarbonate-based dialysate containing a small amount (812 mEq/L) of acetate for stabilization is now used.
  • Sodium acetate may result in cardiovascular instability or blood pressure decrease during dialysis through the peripheral vasodilation, thereby leading to so-called acetate intolerance.
  • sodium bicarbonate dialysate sodium acetate is added in an amount of about 0.4 to 0.7 g / 100 mL, and acetic acid is further added to adjust pH.
  • the acetate concentration in the final dialysate is approximately 8 mEq/L, and the pH is about 7.35.
  • heparin is customarily used to prevent blood coagulation during hemodialysis.
  • hemodialysis when carrying out hemodialysis for patients with a high risk of bleeding, such as those with pericarditis, coagulopathy, thrombocytopenia, cerebral hemorrhage or other bleeding, or those who have recently undergone surgery, it is customary to reduce the amount of heparin in the dialysate or not to use it at all.
  • the mechanism of heparin-free dialysis is to prevent blood coagulation by reducing ionized calcium level in the blood in the extracorporeal circuit.
  • One way of reducing the ionized calcium level in the blood in the extracorporeal circuit is to inject sodium citrate into the arterial circuit and using a dialysate completely free of calcium. In this case, since the blood with very low calcium ion level flows back into the patient, calcium chloride has to be injected to the venous circuit to prevent hypocalcemia.
  • Fig. 1 illustrates the tricarboxylic acid (TCA) cycle by which citric acid is metabolized.
  • TCA cycle is a process in the cellular respiration, by which glycolyzed metabolites of carbohydrate, fat or amino acid are oxidized to store some of energy to adenosine triphosphate (ATP) and to transfer the remainder to the electron transport chain in the from of intermediates such as NAD + , FAD, etc.
  • the cycle was named such because the carbon compound entering the cycle is citric acid having three carboxylic groups. It is also called the citric acid cycle or the Krebs cycle after the name of its discoverer.
  • citrate when citrate is transferred form a dialysate to blood, it may be metabolized in the body by the Krebs cycle to form bicarbonate. Specifically, as citrate is oxidized in the Krebs cycle, two molecules of carbon dioxide are produced, which are dissolved in the blood to form HCO 3 2 . Therefore, a dialysate with a high citrate content may accelerate alkalization of the blood, and a great care is required for patients with alkalosis. In case of bicarbonate-free dialysis, bicarbonate may be released from the blood to the dialysate for the first hour after the onset of dialysis.
  • the bicarbonate level may be maintained at an allowable level during the dialysis.
  • the blood bicarbonate level may increase due to the citrate metabolism. The level continues to increase for hours, as the citrate absorbed from the dialysate is metabolized. Therefore, the inventors of the present invention have developed a method for preparing an acetate-free dialysate capable of reducing citrate level so that it may be used for patients with alkalosis and having a stable acidity around pH 7.35.
  • a dialysate provided for dialysis for patients with renal failure may be prepared by mixing an acidifying agent, an alkalizing agent and purified water at a weight ratio of 1 : 1 ⁇ 1.5 : 30 ⁇ 35 immediately before dialysis.
  • the acidifying agent may be prepared by mixing an alkali metal, an alkaline earth metal, salts thereof, citric acid, an acid for adjusting acidity, and purified water.
  • the acidifying agent may be prepared by dissolving sodium chloride, potassium chloride, calcium chloride, magnesium chloride, citric acid and an acid for adjusting acidity in purified water.
  • the acid for adjusting acidity may be hydrochloric acid, lactic acid, malic acid or a combination thereof.
  • the chloride content of the acidifying agent may be adjusted to 8,000 ⁇ 13,000 mEq/L.
  • the alkalizing agent may be a concentrated aqueous solution of sodium bicarbonate or sodium bicarbonate.
  • the sodium bicarbonate content of the alkalizing agent may be adjusted to 25.0-35.0 mEq/L.
  • the citrate concentration of the dialysate should be adjusted to one sufficiently high to exhibit stable anticoagulant effect during dialysis and, at the same time, to one as low as to prevent alkalization of the blood that may be caused by metabolism of the citrate. Citrate is also an important factor determining acidity of the acetate-free dialysate.
  • dialysate prepared in accordance with the present invention is acetate-free, it does not induce acetate intolerance. Since it provides anticoagulant effect without containing heparin, it may be used for the patients who are at risk of bleeding.
  • concentration of citrate used to provide anticoagulant effect may be adjusted within an allowable range. As a result, alkalosis caused by the metabolism of citrate may be prevented.
  • Fig. 1 schematically shows the tricarboxylic acid (TCA) cycle by which citric acid is metabolized
  • Fig. 2 shows the acidity of the acidifying agent depending on citric acid concentration
  • Fig. 3 shows the acidity of the dialysate depending on citric acid content.
  • Example 1 Acidity of acidifying agent depending on citric acid content
  • An acidifying agent was prepared by dissolving NaCl (21.48 g), KCl (0.65 g), CaCl 2
  • Fig. 2 shows the acidity of the acidifying agent depending on the citric acid content.
  • the pH of the acidifying agent was 5.3 when the citric acid concentration was 0.0 mEq/L.
  • the pH decreased to about 1.3 when the citric acid concentration was 70 mEq/L, and to about 1.1 when citric acid was added at a concentration of 280 mEq/L.
  • the pH decreases to about 4.5 when 280 mEq/L of acetic acid is added to a dialysate as a buffering agent of an acidifying agent, the use of citric acid results in a markedly decreased pH of the dialysate even at low concentration.
  • Acidity of a dialysate prepared by mixing an acidifying agent comprising citric acid, an alkalizing agent and purified water was measured depending on citric acid concentration.
  • a citric acid-free acidifying agent was prepared by dissolving NaCl (21.48 g), KCl (0.65 g), CaCl 2 o 2H 2 O (0.772 g) and MgCl 2 o 6H 2 O (0.53 g) in purified water (100 mL), which was mixed with an alkalizing agent containing 7 g / 100 mL of sodium bicarbonate and purified water, at a weight ratio of 1 : 1.26 : 32.74. Then, citric acid was added to the mixture.
  • the pH of the final mixture solution was measured at various citric acid concentrations.
  • its acidity should be adjusted to normal pH range of arterial blood. Since the normal pH range of the arterial blood is 7.25 ⁇ 7.45, there is a concern of acidosis if the pH of the dialysate is lower than 7.25, and there is a concern of alkalosis if the pH of the dialysate is higher than 7.45.
  • Table 1 shows the acidity of the dialysate depending on the citric acid content
  • Fig. 3 shows the acidity of the dialysate depending on citric acid content.
  • the citric acid concentration of the dialysate should be controlled within a very narrow range around 4.5 mEq/L.
  • the blood pH may increase as the citrate diffused into the blood of the patient during dialysis and is metabolized by the citric acid cycle illustrated in Fig. 1, thereby resulting in alkalosis.
  • the citric acid concentration should be controlled such that the pH of the dialysate is maintained within the normal pH range of the arterial blood, while being the minimum concentration required to prevent blood coagulation or higher, and being not too high to cause alkalosis.
  • Example 3 Optimization of dialvsate composition comprising citric acid and other acid for adjusting acidity
  • the citric acid concentration of the dialysate should be at least 0.1 mEq/L to exhibit anticoagulant effect. And, if the blood citric acid concentration exceeds 5.0 mEq/L, alkalosis may occur as the citric acid is metabolized. Accordingly, the citric acid concentration of the dialysate should be adjusted to 0.1 ⁇ 5.0 mEq/L, more preferably 0.5 ⁇ 2.5 mEq/L.
  • a dialysate having a citric acid content within this range exhibits a pH value of about 9.0 ⁇ 9.4, which is considerably higher than the normal pH of the arterial blood, which is about 7.35. Accordingly, as a way of attaining a dialysate with a pH about 7.35 while maintaining a citric acid concentration providing anticoagulant effect but not inducing alkalosis, addition of an acid for adjusting acidity of the dialysate may be considered. However, acetic acid is excluded from the acid for adjusting acidity because it may induce acetate intolerance.
  • the inventors of the present invention have selected hydrochloric acid, lactic acid and malic acid as the acid added to adjust the acidity of the dialysate, and investigated the acidity of the final dialysate while varying their concentrations in the dialysate.
  • an acidifying agent comprising citric acid was mixed with an alkalizing agent and purified water to prepare a dialysate. While varying the citric acid concentration of the dialysate within 1 ⁇ 5 mEq/L, the effect of the addition of the acid for adjusting acidity was measured.
  • NaCl 22.50 g
  • KCl 0.522 g
  • CaCl 2 O 2H 2 O 0.644 g

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical & Material Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Molecular Biology (AREA)
  • Inorganic Chemistry (AREA)
  • Dermatology (AREA)
  • External Artificial Organs (AREA)
  • Medicinal Preparation (AREA)

Abstract

L'invention porte sur un procédé de préparation d'un dialysat exempt d'acétate qui est stable sans induire de précipitation de calcium dans le sang. Le procédé de préparation comprend le mélange d'un agent acidifiant préparé par la dissolution de chlorure de sodium, de chlorure de potassium, de chlorure de calcium, de chlorure de magnésium, d'acide citrique et d'un acide destiné à ajuster l'acidité dans de l'eau purifiée par un agent alcalisant contenant du bicarbonate de sodium et de l'eau purifiée, pour ainsi préparer un dialysat de pH 7,25 à 7,45. La concentration en acide citrique du dialysat est de 0,5 à 2,5 mEq/l, et l'acide ajouté pour ajuster l'acidité peut être choisi dans un groupe constitué par l'acide chlorhydrique, l'acide lactique, l'acide malique ou une combinaison de ceux-ci. On prépare ainsi un dialysat qui peut empêcher la coagulation du sang, une intolérance à l'acétate et une alcalose durant une dialyse.
PCT/KR2008/006741 2008-11-17 2008-11-17 Procédé de fabrication d'une composition de dialysat exempt d'acétate WO2010055963A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
PCT/KR2008/006741 WO2010055963A1 (fr) 2008-11-17 2008-11-17 Procédé de fabrication d'une composition de dialysat exempt d'acétate

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR2008/006741 WO2010055963A1 (fr) 2008-11-17 2008-11-17 Procédé de fabrication d'une composition de dialysat exempt d'acétate

Publications (1)

Publication Number Publication Date
WO2010055963A1 true WO2010055963A1 (fr) 2010-05-20

Family

ID=42170090

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/KR2008/006741 WO2010055963A1 (fr) 2008-11-17 2008-11-17 Procédé de fabrication d'une composition de dialysat exempt d'acétate

Country Status (1)

Country Link
WO (1) WO2010055963A1 (fr)

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012053942A1 (fr) * 2010-10-18 2012-04-26 Общество С Ограниченной Ответственностью "Научно-Производственное Объединение "Нефрон" Solutions pour hémodialyse au bicarbonate
WO2013058674A1 (fr) * 2011-10-17 2013-04-25 Общество С Ограниченной Ответственностью "Нпо "Нефрон" Solution pour hémodialyse au bicarbonate
KR20140107316A (ko) * 2011-12-21 2014-09-04 감브로 룬디아 아베 투석 전구체 조성물
US8927505B2 (en) 2008-07-07 2015-01-06 Pentec Health, Inc. Nutritive compositions and methods of using same
US9326963B2 (en) 2008-07-07 2016-05-03 Pentec Health, Inc. Nutritive compositions and methods of using same
US9452149B2 (en) 2012-03-08 2016-09-27 Gambro Lundia Ab Dialysis composition comprising citrate, calcium and magnesium
US9616161B2 (en) 2011-06-20 2017-04-11 Gambro Lundia Ab Dialysis precursor composition
US9821102B2 (en) 2011-06-20 2017-11-21 Gambro Lundia Ab Dialysis precursor composition
US9833470B2 (en) 2011-12-21 2017-12-05 Gambro Lundia Ab Dialysis precursor composition
US9925155B2 (en) 2012-12-18 2018-03-27 Gambro Lundia Ab Dialysis composition
US10993961B2 (en) 2010-06-23 2021-05-04 Gambro Lundia Ab Dialysis precursor composition
US11253543B2 (en) 2010-06-23 2022-02-22 Gambro Lundia Ab Dialysis precursor composition product

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4489535A (en) * 1980-10-02 1984-12-25 Veltman Preston Leonard Materials and method for preparing dialysis solutions containing bicarbonate ions
US5211643A (en) * 1989-05-26 1993-05-18 Fresenius Ag Sodium bicarbonate containing precipitate-free dialysis solutions
US5385564A (en) * 1992-10-05 1995-01-31 Fresenius Usa, Inc. System for preparation and use of dialysis solution

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4489535A (en) * 1980-10-02 1984-12-25 Veltman Preston Leonard Materials and method for preparing dialysis solutions containing bicarbonate ions
US5211643A (en) * 1989-05-26 1993-05-18 Fresenius Ag Sodium bicarbonate containing precipitate-free dialysis solutions
US5385564A (en) * 1992-10-05 1995-01-31 Fresenius Usa, Inc. System for preparation and use of dialysis solution

Cited By (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8927505B2 (en) 2008-07-07 2015-01-06 Pentec Health, Inc. Nutritive compositions and methods of using same
US9326963B2 (en) 2008-07-07 2016-05-03 Pentec Health, Inc. Nutritive compositions and methods of using same
US9937125B2 (en) 2008-07-07 2018-04-10 Pentec Health, Inc. Intradialytic parenteral nutrition compositions
US11253543B2 (en) 2010-06-23 2022-02-22 Gambro Lundia Ab Dialysis precursor composition product
US10993961B2 (en) 2010-06-23 2021-05-04 Gambro Lundia Ab Dialysis precursor composition
WO2012053942A1 (fr) * 2010-10-18 2012-04-26 Общество С Ограниченной Ответственностью "Научно-Производственное Объединение "Нефрон" Solutions pour hémodialyse au bicarbonate
US9655922B1 (en) 2011-06-20 2017-05-23 Gambro Lundia Ab Dialysis precursor composition
US9616161B2 (en) 2011-06-20 2017-04-11 Gambro Lundia Ab Dialysis precursor composition
US9821102B2 (en) 2011-06-20 2017-11-21 Gambro Lundia Ab Dialysis precursor composition
WO2013058674A1 (fr) * 2011-10-17 2013-04-25 Общество С Ограниченной Ответственностью "Нпо "Нефрон" Solution pour hémodialyse au bicarbonate
US9463202B2 (en) 2011-12-21 2016-10-11 Gambro Lundia Ab Dialysis precursor composition
US9687507B2 (en) 2011-12-21 2017-06-27 Gambro Lundia Ab Dialysis precursor composition
US9833470B2 (en) 2011-12-21 2017-12-05 Gambro Lundia Ab Dialysis precursor composition
US10172881B2 (en) 2011-12-21 2019-01-08 Gambro Lundia Ab Dialysis precursor composition
KR101978011B1 (ko) 2011-12-21 2019-05-13 감브로 룬디아 아베 투석 전구체 조성물
KR20140107316A (ko) * 2011-12-21 2014-09-04 감브로 룬디아 아베 투석 전구체 조성물
US9724298B2 (en) 2012-03-08 2017-08-08 Gambro Lundia Ab Method to form a dialysis composition comprising citrate, calcium and magnesium
US9452149B2 (en) 2012-03-08 2016-09-27 Gambro Lundia Ab Dialysis composition comprising citrate, calcium and magnesium
US9925155B2 (en) 2012-12-18 2018-03-27 Gambro Lundia Ab Dialysis composition

Similar Documents

Publication Publication Date Title
WO2010055963A1 (fr) Procédé de fabrication d'une composition de dialysat exempt d'acétate
ES2322689T3 (es) Uso de un dializado con elevado contenido de citrato.
TWI583378B (zh) 透析酸前驅物組成物、其用途、以及提供透析酸濃縮物溶液之方法
TWI500424B (zh) 透析前驅物組成物
US20040121982A1 (en) Biocompatible dialysis fluids containing icodextrins
WO2010112570A1 (fr) Solution de dialyse
JP2009131669A (ja) 単一容器中にある重炭酸塩ベースの溶液
JP5204359B2 (ja) 透析用剤およびその製造方法
US20120022423A1 (en) Multipart fluid system and a system for regional citrate anticoagulation in an extracorporeal blood circuit
WO2010112547A1 (fr) Composition précurseur de dialyse
EP2991640B1 (fr) Système de fluide à parties multiples et système d'anticoagulation au citrate dans un circuit sanguin extracorporel
JP2003339853A (ja) 安定な透析用剤
JP6425661B2 (ja) 透析組成物
Gatchalian et al. Management of hypophosphatemia induced by high-flux hemodiafiltration for the treatment of vancomycin toxicity: intravenous phosphorus therapy versus use of a phosphorus-enriched dialysate
JP5371278B2 (ja) 透析用剤およびその製造方法
Oudemans-van Straaten et al. Anticoagulation for renal replacement therapy: different methods to improve safety
EP1318821B1 (fr) Liquide pour hemofiltration
KR101300738B1 (ko) 초산이온을 함유하지 않는 투석용액 조성물의 제조방법
Oudemans-van Straaten Review and guidelines for regional anticoagulation with citrate in continuous hemofiltration
US10463779B2 (en) Multipart fluid system and a system for regional citrate anticoagulation with a phosphate comprising anticoagulation fluid
Vicente et al. The Role of Sustained Low-Efficiency Dialysis (SLED) in the Intensive Care Unit
Michaud et al. Four percent trisodium citrate as an alternative anticoagulant for maintaining patency of central venous hemodialysis catheters: case report and discussion
Fealy Regional citrate anticoagulation

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 08878146

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 08878146

Country of ref document: EP

Kind code of ref document: A1