Principles and Benefits of Citrate Anticoagulation
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1 Principles and Benefits of Citrate Anticoagulation Buddy-Joe Paris Clinical Nurse Specialist Fresenius Medical care Edinburgh Critical Care, Research Group: What s new in ICU
2 The Use of Citrate Citrate has been used for many years across a variety of medical applications, for example, it is widely used for the storage of red blood cells 22 As early as 1990, clinicians began to see the possibilities for utilising citrate as a regional anticoagulant in CRRT 1 Fresenius has extensive experience with regional citrate anticoagulation, with the commercial launch of Ci-Ca in February 2006 after many years of research and development Page 2
3 The Citrate-Calcium Complex Anticoagulation with citrate utilises a process called chelation + Ca + Citrate forms a complex with the Ca 2+ ions, making them unavailable as a co-factor within the clotting cascade Page 3
4 Calcium and the Clotting Cascade Page 4
5 What Are We Doing in Citrate Anticoagulation? Blood is removed via the access line and citrate is added Remaining citrate-calcium complexes are metabolised to bicarbonate and the calcium is released Citrate complexes with calcium and prevents clotting Calcium is replaced in the return line 50% of the citrate-calcium complexes are removed by the filter Page 5
6 Fresenius Ci-Ca CVVHD Circuit Citrate solution is introduced after the access connection Calcium solution is infused just prior to the return connection Anticoagulation is achieved in the circuit, but the patient s clotting status is unaffected Page 6
7 Fluids for Ci-Ca Therapy 4% Sodium Citrate Contains 136 mmol/l citrate Ci-Ca Dialysates calcium free, 4 types Calcium Chloride 100 mmol/l Page 7
8 Fluids for Citrate Therapy Sodium and bicarbonate are reduced to compensate for the systemic infusion of sodium citrate Calcium-free to minimise the citrate requirement Slightly increased magnesium as citrate also chelates with magnesium Page 8
9 Backed by Experts KDIGO AKI Guideline 2, 2012: We suggest using CRRT, rather than standard intermittent RRT, for hemodynamically unstable patients. Oudemans-van Straaten et al. 3, 2011: The full advantage of citrate anticoagulation can only be realized, however, if its risks are well controlled by means of a sound protocol, well-trained staff, and the incorporation of a citrate module in the CRRT device. Zhang & Hongying 4, 2012: Regional citrate anticoagulation is superior to systemic heparin concerning circuit life and risk of bleeding. Link et al. 6, 2012: Regional citrate anticoagulation is an effective and safe alternative to heparin. Morgera et al. 7, 2009: [The Ci-Ca CVVHD protocol] enabled an effective treatment of acute renal failure and excellent control of acid-base status as well on the systemic ionized calcium in combination with negligible clotting issues. Page 9
10 Backed by Experts Kalb et al. 8, 2013: In conclusion, the [Ci-Ca CVVHD] protocol is effective to guarantee very long filter running times enabling the delivery of high dialysis doses. Schultheiß et al. 9, 2012: The sodium balance was stable during [Ci-Ca] CVVHD treatment, with sodium values being within the reference range [ ] in 91 % of runs after 72 hours. Schmidt et al. 10, 2012: The EMiC2 provides superior middle molecule elimination compared to the AV 1000S dialyzer without significant difference in albumin elimination. Raimundo et al. 11, 2013: In conclusion, [the Ci-Ca CVVHD] protocol with target systemic ionised calcium concentration in the physiologic range maintains stable PTH levels. Rimmele et al. 12, 2012: The removal of middle molecular weight molecules is higher with SHF-HD [i.e. CVVHD using EMiC2]. Albumin loss was limited in both groups, even with SHF-HD. Page 10
11 Benefits of Regional Citrate Anticoagulation Delivery of prescribed dialysis dose through long and reliable filter running times 8 Continuous uninterrupted treatment through minimised clotting events and fewer treatment interruptions 4, 13, 18 Reduced risk of bleeding - compared to systemic anticoagulation with heparin, allowing treatment even where heparin is contraindicated e.g. HIT 4, 15, 16, 17, 18 Fewer blood transfusions - related to less bleeding incidents and re-priming of circuits) compared to heparin 15, 16, 17, 18 Nursing time released for patient care through reduction in machine interactions when compared with heparin 8, 19 Prolonged lifespan of the extracorporeal circuit reducing circuit usage compared to heparin 4, 13, 18 Lower blood flow rates with CVVHD compared to CVVH - smaller access catheter to be used Page 11
12 Patient Selection All patients.. but especially Patient s pre- or postoperatively where systemic anticoagulation may be contraindicated Patients with significant coagulopathy related to sepsis, large volume transfusion etc. Trauma patients with potentially undiagnosed bleeding points Patients where surgical wound healing may be compromised by systemic anticoagulation Patients with profound cardiovascular instability for whom high blood flows would be detrimental Page 12
13 Regional Citrate Anticoagulation in CRRT Management of Citrate Anticoagulation with multifiltrate Ci-Ca UK/ABT/MFT/0415/0005
14 Fully Integrated Citrate & Calcium Pumps to Safeguard Page 15
15 Integrated Citrate & Calcium Lines to Safeguard Page 16
16 Mechanically Different Citrate & Calcium Connectors to Safeguard Page 17
17 Colour Coded Connectors to Safeguard Page 18
18 Maintaining Dialysis and Blood Flow Rates The dialysate to blood flow ratio should be at a constant numerical ratio of 20:1 (corresponding to a physical flow ratio of 1.3) If the patient s acid-base balance is deranged this ratio can be adjusted Page 19
19 Display During Citrate Anticoagulation Page 20
20 Post-Filter Ionised Calcium Page 21
21 Adjust the Citrate Flow Page 22
22 Systemic Ionised Calcium Page 23
23 Adjust the Calcium Flow Page 24
24 Regional Citrate Anticoagulation in CRRT Clinical Signs of Poor Citrate Metabolism and the Management Strategy With multifiltrate Ci-Ca UK/ABT/MFT/0415/0005
25 Potential Complications of Citrate Anticoagulation Heparin Induced Thrombocytopenia occurs in 3 5% of patients receiving standard heparin therapy 20 Reduced citrate metabolism occurs in 3.6% of patients 21 Page 26
26 Poor Citrate Metabolism The clinically diagnosable parameters that indicate impaired citrate metabolism are: Decreasing systemic ionised calcium level despite increasing calcium supplementation as per protocol Increased systemic total calcium A total calcium to ionised calcium ratio above 2.25 (this will be checked by the renal team / consultant) Increasing metabolic acidosis If the patient demonstrates any of the above clinical signs, or the calcium infusion rate is running at greater than 2.1mmol/L, this could be indicative of poor citrate metabolism Page 27
27 Possible Strategy for Poor Citrate Metabolism Page 28
28 Revised Sliding Scale for Poor Citrate Metabolism Page 29
29 Regional Citrate Anticoagulation in CRRT Using Citrate to Manipulate Acid-Base Balance UK/ABT/MFT/0415/0005
30 Maintaining Dialysis and Blood Flow Rates The dialysate to blood flow ratio should be at a constant numerical ratio of 20:1 (corresponding to a physical flow ratio of 1.3) If the patient s acid-base balance is deranged this ratio can be adjusted Page 31
31 Managing an Acidosis First review the patient, treat any underlying condition and ensure dialysate dose is appropriate Check that the dialysate and blood flow rates are set according to the protocol To correct an acidosis either: Decrease the dialysate flow (a decrease of 20% will increase the serum bicarbonate level by approximately 4mmol/L) or Increase the blood flow rate (an increase of 20% to the blood flow rate will increase the serum bicarbonate level by approximately 4mmol/L) Page 32
32 Managing an Alkalosis First review the patient, treat any underlying condition and ensure dialysate dose is appropriate Check that the dialysate and blood flow rates are set according to the protocol. To correct an alkalosis either: Increase the dialysate flow (an increase of 20% will decrease the serum bicarbonate level by approximately 4mmol/L) or Decrease the blood flow rate (a decrease of 20% to the blood flow rate will decrease the serum bicarbonate level by approximately 4mmol/L) Page 33
33 Thank You UK/ABT/MFT/0415/0005
Replacement post-filter (ml/hr) Blood flow (ml/min) Dialysate (ml/hr) Weight (kg)
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