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Citrasate

Citrasate - The most prescribed citric acid concentrate

Citrasate is an acid concentrate that contains a small amount of citric acid that provides mild anticoagulation in the extracorporeal circuit.

Citric acid is an anticoagulant. Its presence in the dialysate in 2.4 mEq/L concentration provides some anticoagulation effect in the dialyzer and venous blood line that is quickly neutralized upon reentry into the systemic circulation.

Citrasate is particularly helpful for hemodialysis patients with:
• HIT - Heparin Induced Thrombocytopenia
• Heparin antibodies
• Severe clotting problems
• Bleeding risk factors such as; active bleeding (GI bleeding), trauma and pre / post surgery
• Works well with SLEDD (Sustained, Low-Efficiency, Daily Dialysis)

  • How Citrasate works
  • Formulations
  • Studies
  • FAQs
  • Helpful Hints
  • Additives
  • Guidelines
  • H.I.T.
  • MSDS

How Citrasate Works

Citrasate acid concentrate contains less acetate than regular dialysate (0.3mEq/L). Citrasate contains a small quantity of citric acid (2.4 mEq/L) which provides mild anticoagulation where needed, in the extracorporeal circuit, not systemically in the patient.

Dialysate Composition (mEq/L) Regular Dialysate CITRASATE
Sodium 137 137.3
Chloride 105.5 105.5
Calcium 2.5 2.5
Magnesium 1.0 1.0
Potassium 2.0 2.0
Dextrose (g/L) 2.0 2.0
Acetate 4.0 0.3
Citrate 0 2.4
Bicarbonate 37 37


Citrasate is not the same as regional citrate anticoagulation

Performing citrate dialysis is no different operationally than doing regular bicarbonate dialysis. There is no regional infusion of citric acid employed. Some anticoagulant (citrate) is in the dialysate.

You do not need to be concerned about hypocalcemia
The concentration of citrate in Citrasate® is only 2.4 mEq/L; only about one-fifth of the concentration used to achieve anticoagulation via traditional regional citrate infusions. The use of Citrasate® does not produce measurable systemic anticoagulation, the anticoagulant effect is confined to the dialyzer and the venous side of the dialysis set up. Citrasate® generally produces a clinically acceptable transitory reduction (about 10%) in ionized calcium1. Ionized calcium begins to normalize to the pre-dialysis level as soon as the Citrasate® dialysis session stops1. The consistent treatment of chronic dialysis patients with Citrasate® has demonstrated no change over extended time periods in either total or ionized serum calcium levels1.
(1) Ahmad S, Callan R, Cole JJ, Blagg CR. Dialysate made from Dry Chemicals using Citric Acid Increases Dialysis Dose. American Journal of Kidney Diseases 2000; 35: 493-499

Citrasate Formulations

Citrasate is available in both major hemodialysis dilutions, 36.83X and 45X.
Please refer to your current acid concentrate label for the correct dilution.
If you do not see a formulation that meets your needs, Citrasate can be "spiked" with additives to raise the bath to meet your needs. Dial Medical recommends Edlaw additives for use with Citrasate.

Formula Dilution Na Ca K Mg Chloride Dex Acetate Citrasate
CS-1003-01 36.83X 80.3 2.5 2.0 1.0 85.5 200 0.3 2.4
 
CS-2001-01 45X 100.3 2.5 0.0 1.0 1003.5 200 0.3 2.4
CS-2003-01 45X 100.3 2.5 2.0 1.0 105.5 200 0.3 2.4
CS-2033-01 45X 100.3 3.0 3.0 1.0 107.0 200 0.3 2.4
Now Available in 100 Dextrose
CS-2502-01 45X 100.3 2.5 2.0 1.0 105.5 100 0.3 2.4
CS-2133-01 45X 100.3 3.0 3.0 1.0 107.0 100 0.3 2.4
Citrasate - 1000 Series
Citrasate 1000 series acid concentrate is formulated to be used with a three stream hemodialysis machine calibrated to an acid concentrated dilution ratio of 1:35.83. It must be used in conjunction with a sodium bicarbonate solution providing the desired ionic composition of both Sodium and Bicarbonate. Final mix at time of dialysis will consist of 1 part acid concentrate liquid with 1.83 parts of bicarbonate concentrate and 34.0 parts purified water that meets AAMI standards for dialysis water.
Citrasate - 2000 Series
Citrasate 2000 series acid concentrate is formulated to be used with a three stream hemodialysis machine calibrated to an acid concentrated dilution ratio of 1:44. It must be used in conjunction with a sodium bicarbonate solution providing the desired ionic composition of both Sodium and Bicarbonate. Final mix at time of dialysis will consist of 1 part acid concentrate liquid with 1.72 parts of bicarbonate concentrate and 42.28 parts purified water that meets AAMI standards for dialysis water.

Frequently Asked Questions About Citrasate
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Is Citrasate® cleared for clinical use by the FDA?
Yes.

How do I adapt my present dialysis system to allow the use of Citrasate®
No adaptations are necessary. Citrasate® concentrate is available in standard concentrations and formulations. Simply use the jug provided or pour it into your standard A concentrate container and attach it to your dialysis system as you always do. Keep in mind, with a higher dialysate flow rate more citrate, in relation to the blood, passes through the dialyzer, thus providing more anticoagulation.
What steps are necessary before dialysis with Citrasate® can be started?
Citrasate® may be used in existing dialysis systems without altering them. There is no additional patient or system monitoring needed beyond that normally employed in treatment with standard dialysate formulations. Consequently, no staff training is necessary for the conversion to citrate dialysate.

Can Citrasate® be "spiked" with potassium or calcium?
Yes, it can be spiked just as you do with traditional dialysate concentrates

Is it necessary to check clotting times when Citrasate® is used?
No.

Is there reason to be concerned about bleeding risk, hypocalcemia, or hypomagnesemia when treating patients with Citrasate®?
No. There is no risk of bleeding or low blood mineral levels from citrate use, because the concentration of citrate in the dialysate is well below the level needed to produce anticoagulation of the patient's blood.

Can dialysate flow affect Citrasate's anticoagulation benefit?
With a higher dialysate flow rate (600, 700, 800) more citrate, in relation to the blood, passes through the dialyzer,
thus providing more anticoagulation. With SLEDD treatments, longer clot free runs have been achieved when the dialysate flow is at least 175% of the blood flow rate.

How is Citrasate supplied?
Citrasate® is a liquid "A" concentrate, available in 1 gallon jugs, in concentrations of 36.83X and 45X. The jugs are packed four to the case. Please contact Dial Medical customer service at 800-346-2080 or by e-mail - info@dialmedsupply.com. for more information.

How does citrate dialysate provide the noted patient benefits?
Citric acid is an anticoagulant. Its presence in the dialysate in 2.4 mEq/L concentration provides some anticoagulation effect in the dialyzer and venous blood line that is quickly neutralized upon reentry into the systemic circulation.

Is Citrasate® the same as regional citrate anticoagulation?
No. Performing dialysis with Citrasate® is no different operationally than doing regular dialysis. There is no regional infusion of citric acid employed. "It's all in the dialysate."

Do we need to be concerned with hypocalcemia?
No. The concentration of citrate in Citrasate is only 2.4mEq/L; about one-fifth of the concentration used to achieve anticoagulation via traditional regional citrate infusions. The use of Citrasate does not produce measurable systemic anticoagulation; the anticoagulant effect is confined to the dialyzer and the venous side of the dialysis set-up. Citrasate generally produces a clinically acceptable transitory reduction (about 10%) in ionized calcium (ref 1). Ionized calcium begins to normalize to the pre-dialysis level as soon as the Citrasate dialysis session stops (ref 1). The consistent treatment of chronic dialysis patients with Citrasate has demonstrated no change over extended time periods in either total or ionized serum calcium levels (ref 1).
References:1. Ahmad S, Callan R, Cole JJ, Blagg CR. Dialysate made from dry chemicals using citric acid increases dialysis dose. Am J Kidney Dis. 35(3):493-499, 2000.

Helpful Hints
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Make sure you are using the correct dilution (36.83X, 45X) and dextrose:
Refer to your current acid concentrate label for the correct dilution and dextrose.

Dialysate flow can affect Citrasate's anticoagulation benefits:
With a higher dialysate flow rate (600, 700, 800) more citrate, in relation to the blood, passes through the dialyzer,
thus providing more anticoagulation. With SLEDD treatments, longer clot free runs have been achieved when the dialysate flow is at least 175% of the blood flow rate.

Be sure to run the Citrasate dialysate through the dialyzer prior to starting the treatment
This will "coat" the dialyzer with citric acid to aid in anticoagulation.

Citrasate may be used in conjunction with heparin:

The use of Citrasate and heparin together may produce superior anticoagulation results vs. heparin alone.

Citrasate and patients with advanced liver failure:
The low citrate concentration (2.4mEq/L) in Citrasate, coupled with citrate metabolism in the muscles produces no evidence of citrate accumulation in the patient. Abstract available at www.citrasate.com/references

Citrasate and Catheter patients:
Temporary Catheters may diminish the effectiveness of Citrasate because they require low flow rates (max 200 - 300), are hard to use and tend to kink easily.

Citrasate is a dialysate concentrate. Citrasate is not a catheter "lock".

Storing unused Citrasate:
Unused Citrasate should be kept in a sealed container and can be used up to the expiration date on the label

Citrasate may be "spiked" with potassium or calcium:
Please refer to your additive supplier's directions or contact Dial Medical for more information.

Conductivity alarm with Gambro Phoenix machines:
You might experience conductivity alarms with Gambro Phoenix dialysis machines, caused by a slight pH difference (higher) in Citrasate dialysate. NOTE: No other machine has this issue. The problem is with the machine setting, not Citrasate. There is a circuit board setting in the machine that can be adjusted to the "upper" 7.8 pH range. Contact your Gambro technician to adjust the setting.

Citrasate may not work on all patients:
A 75 - 80% success rate with heparin-free treatments has been routinely achieved in clinical studies. For example, in one published study with regular dialysate, about 24% of acute patients treatments were completed compared to 76% not completed due to clotting in the extracorporeal circuit. With CITRASATE®, a statistically significant 78% of the treatments were completed. Hence, CITRASATE® treatment dramatically improves and simplifies clinical treatment in this high-risk patient group (Tu A, Ahmad S, Heparin-free hemodialysis with citrate containing dialysate in intensive care patients. Dial Transplant. 2000; 29(5): 991-999.)

Not all dialyzers are created equal:
With the REXEED dialyzer, Asahi has achieved a new level of overall performance in dialyzer design by combining the new polysulfone membrane, REXBRANE, with a new jacket design allowing for optimum flow dynamics. Incorporated on the inner surface is Asahi's unique hydrophilic gel layer technology. This minimizes blood membrane interaction and plays a crucial roll in ANTICOAGULATION requirements, LESS HEPARIN!!

Citrasate and Additives
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Additives can be used with Citrasate to adjust the dialysate bath to the desired milliequivalent (mEq+) level. Edlaw's pre-measured packets can alter (spike) a stock gallon of Citrasate concentrate to the exact physiological needs of the patient.

  • All packets are color-coded for safety and have directions for use

  • All boxes include instruction sheets and mEq+ to gram conversion formulas

  • All potassium and calcium chloride boxes include color-coded adhesive labels to indicate which concentration container has been "spiked", by whom, by how much and the date it was done.


How to "spike" a dialysate bath:

  1. Verify physicians order for Potassium and/or Calcium Chloride in dialysate.

  2. If required, have a clinical staff member oversee use and mixing of additive.

  3. Verify size of acid container your facility uses. Citrasate gallons are 3.78 liters.

  4. Determine which electrolyte additive is needed (KCl, CaCl2, etc)

  5. Determine the amount of milliequivalent increase required (.5 mEq/l, 1 mEq/l, etc)

  6. Refer to Edlaw's Hemodialysis Additive Chart or Slide Adjustment Guide to determine the correct gram weight to use.

  7. After the correct gram size has been determined: verify gram weight on additive packet, tear or cut open the packet, dispense all contents into dialysate container and mix / shake until completely dissolved.

  8. Complete Edlaw Potassium and/or Calcium Chloride concentrate adjustment label and affix to each concentrate container

  9. If validation is necessary, lab test the dialysate. This procedure is performed by obtaining a sample of the final dialysate fluid from the dialysis machine after conductivity has been reached and sodium modeling is turned off. Send sample to a lab for validation.

 

To order Edlaw additives for any of your dialysis needs, fax your order to 610-827-0987.

Guidelines For The Use of Citrasate
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Citrasate® contains a small amount of anticoagulant (citric acid) and thereby can provide some anticoagulation benefit for the extracorporeal hemodialysis circuit in cases where heparin is contraindicated or is ineffective. Such cases include but not limited to:

  • Heparin Induced Thrombocytopenia (HIT)

  • Heparin allergies

  • Risk of bleeding (trauma, surgery, GI bleed, or where heparin has proven ineffective in preventing clotting of the extracorporeal circuit).

  • Low platelet count


I. Policy/Procedure:

  1. Citrate dialysate will be ordered by the physician by trained dialysis staff (doctor, nurse or technician) under the following conditions:

    • For patients with Heparin-induced Thrombocytopenia (HIT).

    • For patients with diagnosed or suspected allergy to heparin.

    • When heparin is either contraindicated or is prescribed in a low dose, due to some risk of bleeding.

    • When heparin is ineffective in preventing clotting of the extracorporeal dialysis circuit to the point where the patient's treatment is adversely affected.

    • To increase dialyzed reuse, especially for poor reuse patients.

  2. Verify physician order, and assure that the correct dialysate, both the concentration - proportioning ratio and formulation, is obtained.

  3. Attach the citrate dialysate jug to dialysis machine using the acid port

  4. Run treatment per physician's prescribed time.

  5. Keep in mind, with a higher dialysate flow rate more citrate, in relation to the blood, passes through the dialyzer, thus providing more anticoagulation.

  6. After treatment is completed, label remaining acid concentrate with time and date or discard remaining acid concentrate.

  7. Documentation:

    Chart dialysate type and normally document treatment in the patient's medical record.

    Additives:

    You can use additives with Citrasate just like you use them for your regular acid concentrate. First, you must determine:

    • Who is allowed to perform the additive mixing (clinical or technical staff or both).

    • The dialysis machine proportioning ratio (36.83X or 45X)

    • The acid container volume (Citrasate gallon jug is 3.785 liters).

    • The chemical composition of your acid concentrate

    • The type of electrolyte additive required, for example (KCl, CaCl2, etc.)


    Calculate (per additive manufacturer's instructions*) the amount of additive needed to raise the desired electrolyte to the level required. Add the additive to the acid container and mix thoroughly. Be sure to label the container with the new electrolyte level. Your spiked Citrasate is ready to use. If required, have clinical staff perform appropriate sign off, showing correct additive was used.

    Rationale/Background:

    • Citrate dialysate contains citric acid - a physiological acid that the body can quickly metabolize and
      which also has anticoagulation properties. The anticoagulation mechanism of citrate dialysate
      occurs because citrate binds to calcium (ionized or "free" calcium), thus removing calcium from
      the blood clotting cascade. Citrate dialysate provides no measurable systemic anticoagulation,
      however its introduction at the dialyzer provides some local anticoagulation benefit in the dialyzer
      and the venous portion of the extracorporeal circuit. Upon reentering the systemic circulation
      blood calcium levels rapidly return to normal.

    • Citrasate® is packaged in ready-to-use 1-gallon jugs. Citrate Dialysate (Citrasate®) contains 2.4
      mEq/L of citrate and 0.3 mEq/L of acetate. Other chemicals are similar to regular dialysate.

    • In many thousands of acute HD treatments done at the University of Washington Medical Center
      over the past 4 years no arrhythmias, clinically significant changes in serum values, or any other
      adverse affects have been reported.

    • Citrasate® has also been used for long-term treatment (up to three years) of chronic hemodialysis
      patients without any adverse changes in blood chemistries or other affects.

    • It has been reported (Ahmad et al) that the use of citrate dialysate may temporarily (during dialysis)
      decrease ionized calcium levels by approximately 10% and may, particularly with repeated long-
      term treatment, increase bicarbonate levels. Citrate is also known to bind with magnesium.
      Therefore, particularly in the inpatient setting, you may want to monitor these factors, but this is
      not routinely necessary.


    II. Cautions:

    Although very rarely occurring, be aware of symptoms of a patient reaction to citrate: During treatment assess the patient for signs of hypocalcemia; numbness/tingling around the mouth, unusual muscle cramps (in length or severity). If symptoms occur, place machine in bypass and notify the doctor. Symptoms should resolve within minutes because any excess citrate is quickly metabolized.

    References:

    1. Tu A, Ahmad S. Heparin-free hemodialysis with citrate-containing dialysate in intensive care patients. Dialysis & Transplantation, 29(10):620-624, 2000.

    2. Ahmad S et al. Dialysate made from dry chemicals using citric acid increases dialysis dose. Am J Kidney Dis. 35(3):493-499, 2000.

    3. O'Shea S, et al. Alternative Methods of Anticoagulation for Dialysis-dependent Patients with Heparin-induced Thrombocytopenia. Seminars in Dialysis, Vol. 16, No 1, 61-67, 2003.

    4. Mureebe L, et al. Heparin-associated antiplatelet antibodies increase morbidity and mortality in hemodialysis patients. Surgery, Vol. 136, No. 4:848-853, 2004.

    5. Ahmad S, et al. Increased Dialyzer Reuse with Citrate Dialysate. Hemodialysis International, in press.

Treating Hemodialysis Patients with Heparin-Induced Thrombocytopenia (HIT)
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Heparin is used extensively in dialysis, most commonly for:
• Bolus heparin infusions pre dialysis
• Intermittent bolus during treatment
• Locking dose of heparin for catheters post treatment
• Heparinization of dialyzers and blood tubing set pre dialysis

HIT occurs in 3% of patients who receive intravenous unfractionated heparin for treatment of deep vein thrombosis or pulmonary embolism.1 Lesser heparin exposures such as; prophylactic subcutaneous doses, flushes to maintain arterial catheter patency and even the tiny amounts of heparin that leach from coated vascular catheters, produce HIT in 0.5% of patients.

In HIT, platelet counts fall by more than 30% within 5 to 12 days after initial exposure to heparin. The degree of thrombocytopenia is highly variable. Thrombocytopenia often is moderate (80 to100 X 103/μL) and thus easily overlooked in an ICU or postoperative patient. However, modest thrombocytopenia may be the first clue to an impending HIT-related catastrophe. In one study 2, many of the patients with HIT had platelet counts at or below 20 X 103/μL, but bleeding was rare. Thirty percent to 75% of patients with HIT experience venous or arterial thromboemboli at the same time as or following the reduction in platelet count.(3 , 4)

Warkentin suggests that up to 25% of patients with heparin-induced thrombocytopenia may suffer some acute systemic reaction to heparin, such as chills, rigors, fever, hypertension, tachycardia, flushing, diaphoresis, nausea, myalgias, even transient global amnesia; these reactions are sometimes preceded by inflamed lesions at subcutaneous injection sites. (5, 6, 7) There have been reports of acute cardio-respiratory collapse from heparin since its introduction into clinical practice. (8, 9, 10 11)

Currently, dialysis treatments use saline flushes (generally ineffective) or regional citrate anticoagulation (dangerous expensive and labor intensive) to avoid using heparin.
Citrasate, a new acid concentrate for bicarbonate dialysis, is unique because it uses citrate in the dialysate.  Citrate is a well-known anticoagulant that functions by binding calcium, thereby reducing the calcium available to participate in the blood clotting mechanism.  Citrasate contains 2.4 mEq/L citric acid; well below the levels employed in regional citrate anticoagulation.  In this concentration citrate dialysate has been successfully used for heparin-free dialysis of patients with antibodies to heparin (12).
Citrasate is a cost-effective alternative for high risk patients who tend to be more costly to treat. These patients can be impacted by blood loss plus treatment may require additional bloodlines, dialyzers and time. Citrasate is also ideal with patients who have bleeding risk factors, i.e. trauma, post-surgery, impending surgery/procedure.

References:

  1. WARKENTIN TE, LEVINE MN, HIRSH JM, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight
    heparin or unfractionated heparin. N Engl J Med 1995;332 (20):1330-5.
  2. RICE L, HUFFMAN DM, LEVINE ML, et al. Heparin-induced thrombocytopenia/thrombosis syndrome: clinical manifestation and
    insights. (Abstr) Blood 1986;68(5 Supply 1):339
  3. WARKENTIN TE, KELTON JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med 1996;101(5):502-7
  4. RICE L, NGUYEN PH, VANN AR. Preventing complications in heparin-induced thrombocytopenia. Post grad Med 2002;112(3)
  5. WARKENTIN TE. Heparin-induced thrombocytopenia: A ten-year retrospective. Annu Rev Med 1999;50:129-147
  6. WARKENTIN TE, SOUTAR RL, PANJU A, GINSBERG JS. Acute systemic reactions to IV bolus heparin therapy: characterization
    and relationship to heparin-induced thrombocytopenia (Abstract). Blood 1992;80 (Supply. 1):160a
  7. LING E, WARKENTIN TE: Intraoperative heparin flushes and subsequent acute heparin-induced thrombocytopenia. Anesthesiol
    1998;89:1567-1569.
  8. CHERNOFF AI. Anaphylactic reaction following injection of heparin. N Engl J Med 1950;242:315-319
  9. BERNSTEIN I. Anaphylaxis to heparin sodium. JAMA 1956;161:1379-1381
  10. CURRY N, BARDANA EJ, PIROFSKY B. Heparin sensitivity: report of a case. Arch Intern Med 1973;132:744-745.
  11. MIM MP, MANIAN P, RICE L. Acute cardio-respiratory collapse from heparin: a consequence of heparin-induced thrombocytopenia.
    Eur J Haematol 2004;72: 366-369
  12. TU A, AHMAD S, Heparin-free Hemodialysis with Citrate-Containing Dialysate in Intensive Care Patients. Dial & Trans 2000; 29:#10

Citrasate MSDS (Material Safety Data Sheets)

Citrasate Material Safety Data Sheets (MSDS)Citrasate Material Safety Data Sheets (MSDS) include information concerning; Generic Product Identification, Hazard overview, Components, Physical data, Fire and explosion data, Reactivity data, Health hazard data, Precautions for safe handling and use and Protective equipment.

Print Citrasate MSDS (PDF)