1. Continuous Renal Replacement Therapy with Citrate

2. Aim of this Workshop
Introduce Citrate and how it works as an anticoagulant for CRRT
The indications and contraindications of the use of Citrate
Different fluids requires during Citrate RRT
Safe monitoring and care of the patient on CRRT

3. Citrate New kid on the block!
Citrates are a family of compounds of which Citric acid and trisodium are the most relevant to RRT
It’s the Citrate molecule of these compounds that will bind to form complexes with ionized calcium and magnesium.
However first seen as an anticoagulant in blood transfusion in 1914
In relation to RRT first reported in studies in the 1960’s by Morita and Colleagues and Appiled to RRT by Methta and colleages in the 1990’s and to date is standard practice in chronic dialysis.
Expanding on that in biochemisty Citric acid plays an important role in the metabolism of all living things to which trisodium critic is a salt of Citric acid.
In the blood calcium circulates primarily either in it’s free form (known as ionized calcuim) or in a form bound to protein.

4. How important is calcium ?
The plasma total calcium concentration range is mmol/l
With normal ionized calcium range being mmol/l
Supports the building and maintenance of strong bones on teeth
Helps muscle contraction
Regulation of blood pressure and heart function
Affects the release of neurotransmitters for nerve conduction
Calcium in it’s ionized form PARTICIPATES IN THE CLOTTING CASCADE
Importance of calcium in the human body to which the body will regulate tight control over through 3 hormones calcitonin, parathyroid hormaone and vit D.
Calcuim levels high body releases calcitonin
Calcuim high PTH and vit D to increse levels.

5. Any Volunteers?????
Ionized calcium forms participates in each of the three pathways (Intrinsic. Extrinsic and common).
When using citrate as an anticoagulation, citrate/ calcium complexes are small molecules and along with some protein bound calcium they will be cleared through the filter and lost in the effluent which must be replaced to prevent hypocalcaemia. (will depamd on blood flow rate,fluid flow rates and filter size).
Therefore citrate inhibits coagulation by binding with calcium and removing a critical component of the coagulation cascade
Aim is to maintain circuit Ionised calcium level below 0.35mmol/L to prevent clot formation

6. Where does the Cal/Cit go?
Some is cleared through the dialysis flow
Any that gets back to the patient is metabolised
There is a risk of causing metabolic alkalosis – but we can sometimes use that to our advantage…
Depending on the treatment mode and flow rates calcium citrate complexes will be cleared by the filter and lost in the effluent.

7. Citrate Metabolism
In the body caluim citrate is main metabolised by the liver and to the lesser extent skeletal muscle and the kidneys.
So therefore will result in an additional alkali to the patient and when ionized calcium is released it becomes available as a coagulation factor in the patients blood, systemic anticoagulation does not occur if serum ionized calcium concnetration is maintained at 1.0=1.3mmol/l.

8. Why Citrate?
Regional anticoagulation and does not affect systemic clotting
Patients with active bleeding, recent bleeding or high risk bleeding (extensive list)
Safe to use during, immediately prior and post surgery
No risk of HIT
Our average circuit life is 39hours

9. Why not Citrate? Cost? Severe Liver Failure Severe Hypoxaemia
Citrate Intolerance
Cost, our evidence suggested that it is cost neutral, if you consider loss of sets blood transfusion etc.
Liver failure – As citrate is metabolised by the liver to which impaired citrate metabolism has been described it is unknown whether cirrhotic patients are at risk of citrate accumulation, however studies have found septic patients tolerate citrate well. Evidence on the WSH unit has found that a raised ALT over 1000 could be a trigger.
Severe Hypoxaemia – think krebs cycle!
Citrate intolerance – very rare and is where a patients inability to metabolised the citrate calcuim complex resulting in decreased ionised calcuim level, increase in total calcium levels and metabolic acidosis.

10. Filter Fluids
Take a look at the mechanism's of action, or how the machine actually works! Although three different makes of machine in use, the principles are the same!

11. Replacement Fluid Electrolytically balanced fluid Pre or Post Dilution
Will vary dependent upon anticoagulation used
Contains normal physiological levels of Sodium, Potassium, Bicarb etc. Phoxilium also contains magnesium and phosphate.
Pre of post dilution – refers to where the replacement fluid is added into the circuit, pre-dilution would be pre filter, post dilution would be after the filter.
Pros and cons to each – discuss
Multifiltrate machine will be either or – depending upon how it is set up
Prismaflex can provide either – this can be adjusted during therapy

12. Dialysis Fluid
Electrolytically balanced fluid – may differ depending upon the type of anticoagulant in use
Does not enter the blood stream
Used in CVVHDF and CVVHD modes
The solution used will differ when citrate is used.

13. CRRT Citrate Fluids
Citrate solution added pre dilution, onto access line
Dialysis solution has a lower HCO3 content.
Replacement fluid remains the same, but usually given post dilution
Calcium Chloride infusion given to maintain ionised calcium in normal range.

14. Citrate Variations Multifiltrate Aquarius Prismaflex
Citrate solution 136mmol/l
Citrate start does 4mmol/l
Calcium solution 100mmol/l
Aquarius
Citrate solution 133mmol/l
Citrate start dose 4mmol/l
Calcium solution 100mmmol/l
Prismaflex
Citrate solution 18mmol/l
Citrate start dose 3mmol/l
Calcium solution 600mmol/l (30mmol/50ml)
Lower citrate into system high fluid volumes.

15. The Citrate Circuit - Multifiltrate

17. The Citrate Circuit - Prismaflex

18. Vascular Access
You can have the most advanced CRRT machine in the world, but if the access is poor – it’s not going to work!
Access devices cost around £50 + doctors time to insert.
A circuit costs around £100 + fluids £10/bg + Anticoagulant + Nurses time – which is priceless…

19. Effluent Dose A measurement to quantify the ‘dose of CRRT’
Calculated as:
Replacement +Dialysis+ Fluid removed (mls)
Patients weight
=Effluent Dose mls/kg
Aim for 35ml/kg.
Renal intensity study suggests no improvement outcomes with larger doses.

20. Starting Citrate CRRT
We are unable to set the volume of citrate going into the circuit – this is determined by the blood pump speed and the required citrate dose

21. Monitoring - General Cardiovascular observations Fluid Balance
BP, Temp, Heart rate & Rhythm
Fluid Balance
Filter observations
Access Pressure
Return Pressure
Blood Pump Speed
Replacement Rate
Dialysis Rate
Effluent Pressure
Fluid Removal
Pressure Drop
Effluent Dose
What do each of these mean?
We will look at troubleshooting these later.

22. Treatment Monitoring
Sample from the patient – usually arterial line (but venous is ok)
Sample from the circuit – post filter

23. Calcium Ratio Total Calcium/Ionised Calcium
Indicates patients ability to metabolise the citrate-calcium
Anything under 2.5 is normal

24. Citrate & Calcium Adjustment
Filter calcium at the top
Patient calcium on the side
Join up the two columns!

25. Scenarios!

26. Bloods at one hour, what would you do?
Do nothing
Increase Citrate and Decrease Calcium
Increase Citrate only
Increase Citrate and Increase Calcium
Patient Ca2+
1.20
Circuit Ca2+
0.60

27. Answer… Filter calcium is too high..
Citrate dose to be increased by 0.5mmol/L
Patient calcium is within normal range

28. When would you sample again?
1 hour
2 hours
6 hours

29. Answer…
Check patient ionised calcium and filter ionised calcium after one hour

30. Repeated bloods, what would you do?
Do nothing
Increase Citrate and Decrease Calcium
Increase Citrate only
Increase Citrate and Increase Calcium
Patient Ca2+
1.25
Circuit Ca2+
0.45

31. Answer… Patient calcium is within normal range, so no change
Filter calcium is within range, so no change

32. When would you sample again?
1 hour
2 hours
6 hours

33. Four hours in…
Lab bloods sent – U&E’s (including Phosphate, Magnesium and Calcium)
Citrate also binds with Magnesium.
Calculate Calcium Ratio

34. pH & Bicarbonate Recap – Citrate-Calcium is metabolised
A buffer load is received
There is a risk of metabolic alkalosis
We can use this to our advantage in acidotic patients

35. Dialysis Flow and Blood Pump Adjustment

36. Blood Results (Lab & ABG) Current Machine Settings
Lets have a go!
Blood Results (Lab & ABG)
pH (ABG)
7.23
HCO3
21.1
Total Calcium
2.2
Ionised Calcium (ABG)
1.25
Calcium Ratio
1.76
Ionised Calcium (Circuit)
0.45
Current Machine Settings
Citrate Dose
3.5
Calcium Compensation
100%
Dialysis
1300
Blood Pump
130
Replacement
500

37. What would you do? Give Sodium Bicarbonate
Decrease dialysis flow and increase blood pump speed
Increase dialysis flow and decrease blood pump speed
Do nothing

38. Decrease Dialysis & Increase Blood Pump
Decreasing the dialysis will reduce the clearance of citrate-calcium – more will go back to the patient
Increasing the blood pump will automatically increase the volume of citrate in the circuit
Both of these will result in the patient metabolising more citrate-calcium, which will provide a larger buffer load

39. Blood Results (Lab & ABG)
Six hours on…
Blood Results (Lab & ABG)
pH (ABG)
7.36
Ionised Calcium (Circuit)
0.45
Total Calcium
2.2
Ionised Calcium (ABG)
1.25
Calcium Ratio
2.8
HCO3 (ABG)
24.3

40. What would you do? Do nothing Stop Filter
Increase dialysis and decrease blood pump
Decrease dialysis and increase blood pump

41. Increase Dialysis & Decrease Blood Pump
Increased dialysis flow will clear more citrate-calcium
Decreasing the blood pump will reduce the volume of citrate in the circuit
The patient will have less citrate-calcium to metabolise
This will sometimes work and sometimes not, occasionally patients are just unable to metabolise the citrate
If the calcium ratio remains high, then stop the circuit and rethink your strategy

42. References
Y.Morita e al. Regional anticoagulation during hemodialysis using citrate. Am J Med Sci 1961;242:32-42
M. Johannidis, H.M. Oudemans-van Straaten. Clinical review: Patency of the circuit in continuous renal replacement therapy. Critical Care, 2007, 11:218.
R. Bellomo, A. Cass, L Cole et al. Intensity of Continuous Renal- Replacement Therapy in Critically Ill Patients (RENAL Trial). NEJM 2009;
Citrate anticoagulation using the Prismflex system with integrated calcium management. Gambro