1. Citrate Anticoagulation
Patrick Brophy MD, MHCDS
Professor & Director Pediatric Nephrology
University of Iowa- Children’s Hospital
London 2015
Brophy University of Iowa

2. Brophy University of Iowa
Objectives
Review rationale for anticoagulation
Options
Available data
Brophy University of Iowa

3. Brophy University of Iowa
Relevance to CRRT
Functional circuit life is imperative to:
Dose delivery
Staff statisfaction
Patient morbidity (changing lines)
Cost of therapy—multi circuit use
Brophy University of Iowa

4. Optimal Anticoagulation
Should be:
Readily available
Consistently delivered (protocols)
Safe!!!!
Easily monitored
Commercially available
Be associated with minimal side effects
Brophy University of Iowa

5. * No antidote known Anticoagulants Saline Flushes Heparin Peds
Citrate regional anticoagulation Peds
Low molecular weight heparin
Prostacyclin
Nafamostat mesilate
Danaparoid*
Hirudin/Lepirudin
Argatroban (thrombin inhibitor)*
* No antidote known
Brophy University of Iowa

6. Brophy University of Iowa

7. Sites of Thrombus Formation
Any blood surface interface
Hemofilter
Bubble trap
Catheter (Especially Pediatrics)
Areas of turbulence resistance
Luer lock connections / 3 way stopcocks
Brophy University of Iowa

8. Brophy University of Iowa
Citrate
Brophy University of Iowa

9. Brophy University of Iowa
How does citrate work
Clotting is a calcium dependent mechanism, removal of calcium from the blood will inhibit clotting
Adding citrate to blood will bind the free calcium (ionized) calcium in the blood thus inhibiting clotting
Common example of this is blood banked blood
Brophy University of Iowa

10. Brophy University of Iowa
Calcium
Dependent
Pathways
CITRATE
Brophy University of Iowa

11. Brophy University of Iowa
How is citrate used?
In most protocols citrate is infused post patient but prefilter often at the “arterial” access of the dual (or triple) lumen access that is used for hemofiltration (HF)
Calcium is returned to the patient independent of the dual lumen HF access or can be infused via the 3rd lumen of the triple lumen access
Brophy University of Iowa

12. Brophy University of Iowa
(Citrate = 1.5 x BFR
150 mls/hr)
(Ca = 0.4 x citrate rate
60 mls/hr) (8mg/ml)
Pediatr Neph 2002, 17:
(BFR = 100 mls/min)
Replacement Fluid
Calcium can be infused in 3rd lumen of triple lumen access if available.
Dialysate
Brophy University of Iowa

13. Citrate: Technical Considerations
Measure patient and system iCa in 2 hours then at 6 hr increments
Pre-filter infusion of Citrate
Aim for system iCa of mmol/l
Adjust for levels
Systemic calcium infusion
Aim for patient iCa of mmol/l
Brophy University of Iowa

14. Brophy University of Iowa
Citrate: Advantages
No need for heparin
Commercially available solutions exist (ACD-citrate-Baxter)
Less bleeding risk
Simple to monitor
Many protocols exist
Brophy University of Iowa

15. Brophy University of Iowa
Advantages of Citrate
Has zero effect upon patient bleeding as opposed to heparin which effects system and patient bleeding
Easy to monitor with ionized calcium assay
Activated Clotting Time (ACT) nor PTT needed
Programs report less clotted circuits = less disposable cost and less overtime nursing hours
Bedside surveys demonstrate less work of machinery allowing more attention to patient
Brophy University of Iowa

16. Brophy University of Iowa
Citrate: Problems
Metabolic alkalosis
Metabolized in liver / other tissues
May be associated with post CRRT raclcitrant hypercalcemia
Electrolyte disorders
Hypernatremia
Hypocalcemia
Hypomagnesemia
Cardiac toxicity
Neonatal hearts
Brophy University of Iowa

17. Complications of Citrate: Metabolic alkalosis
Metabolic alkalosis due to
citrate conversion to HCO3
Solutions with 35 meq/l HCO3
NG losses
TPN with acetate component
Treatment
Solutions with 35 meq/l HCO3
Decrease bicarbonate dialysis rate and replace at the same rate with NS (pH 5)
NG losses
Replace with ½-2/3 NS
TPN with acetate component
Use high Cl ratio
Brophy University of Iowa

18. Complications of Citrate: “Citrate Lock”
Seen with rising total calcium with dropping/Stable patient ionized calcium
Essentially delivery of citrate exceeds hepatic metabolism and CRRT clearance
Treatment of “citrate lock”
Decrease or stop citrate for 1 hr then restart at 70% of prior rate or Increase D or FRF rate to enhance clearance
Brophy University of Iowa

19. Citrate or Heparin: literature
Brophy University of Iowa

20. Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Unfractionated Heparin
Citrate
Brophy University of Iowa

21. Brophy University of Iowa
Anticoagulation
In adults: Monchi M et al. Int Care Med 2004;30:260-65
Median filter life was 70 hr Citrate, 40 hr Heparin
Fewer PRBC transfused in Citrate group (surrogate of bleeding per study) 0.2 units/day of CVVH Citrate vs 1 units/day of CVVH Heparin
Brophy University of Iowa

22. Brophy University of Iowa
Heparin or Citrate? .
Morgera S, et.al. Nephron Clin Pract. 2004; 97(4):c131-6.
single center adults
regional anticoagulation : trisodium citrate vs standard heparin protocol ( customized calcium-free dialysate)
CitACG was the sole anticoagulant in 37 patients, 87 patients received low-dose heparin plus citrate, and 85 patients received only hepACG.
Both groups receiving citACG had prolonged filter life when compared to the hepACG group.
significant cost saving due to prolonged filter life when using citACG.
Brophy University of Iowa

23. Brophy University of Iowa
Seven ppCRRT centers
138 patients/442 circuits
3 centers: hepACG only
2 centers: citACG only
2 centers: switched from hepACG to citACG
HepACG = 230 circuits
CitACG= 158 circuits
NoACG = 54 circuits
Circuit survival censored for
Scheduled change
Unrelated patient issue
Death/witdrawal of support
Regain renal function/switch to intermittent HD
Brophy University of Iowa

24. Brophy University of Iowa

25. ppCRRT ACG Side Effects
Heparin
11 cases of systemic bleeding on heparin
5 cases no ACG used secondary to bleeding
1 case of HIT
Citrate
19 cases of metabolic alkalosis
1 change to heparin for hyperglycemia
1 change to heparin for alkalosis
3 cases of citrate lock
Brophy University of Iowa

26. Anticoagulation and CRRT
Heparin and citrate anticoagulation most commonly used methods
Heparin: bleeding risk
Citrate: alkalosis, citrate lock
Brophy University of Iowa

27. Brophy University of Iowa
Reference Tools
Adqi.net-web site for information on CRRT
AKIN.org
Crrtonline.com-web site for info on Dr Mehta’s meeting
Pediatric CRRT with links to other meetings, protocols, industry
PCRRT list serve (contact Tim Bunchman)
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28. Brophy University of Iowa
Thanks
ppCRRT members
Bedside ICU and Dialysis Nurses
patients
Brophy University of Iowa