Citrate Anticoagulation
Patrick Brophy MD, MHCDS
Professor & Director Pediatric
Nephrology
University of Iowa- Children’s Hospital
London 2015
Brophy University of Iowa
Objectives
 Review rationale for anticoagulation
 Options
 Available data
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
Optimal Anticoagulation
 Should be:
 Readily available
 Consistently delivered (protocols)
 Safe!!!!
 Easily monitored
 Commercially available
 Be associated with minimal side effects
Brophy University of Iowa
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
Brophy University of Iowa
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
Citrate
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
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Calcium
Dependent
Pathways
CITRATE
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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
(Citrate = 1.5 x BFR
150 mls/hr)
(Ca = 0.4 x citrate rate
60 mls/hr) (8mg/ml)
Pediatr Neph 2002, 17:150-154
(BFR = 100 mls/min)
Replacement
Fluid
Dialysate
Brophy University of Iowa
Calcium can be infused in 3rd
lumen of triple lumen access if
available.
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 0.3-0.4 mmol/l
 Adjust for levels
 Systemic calcium infusion
 Aim for patient iCa of 1.1-1.3 mmol/l
 Adjust for levels
Brophy University of Iowa
Citrate: Advantages
 No need for heparin
 Commercially available solutions exist (ACDcitrate-Baxter)
 Less bleeding risk
 Simple to monitor
 Many protocols
exist
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
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
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
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
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Citrate or Heparin: literature
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Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Citrate
Unfractionated Heparin
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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
Heparin or Citrate?
.
 single
center
- 209Nephron
adults Clin Pract. 2004; 97(4):c131-6.
Morgera
S, et.al.
 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
 Seven ppCRRT centers
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

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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
Brophy University of Iowa
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
Anticoagulation and CRRT
 Heparin and citrate anticoagulation most commonly
used methods
 Heparin: bleeding risk
 Citrate: alkalosis, citrate lock
Brophy University of Iowa
Reference Tools

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

Adqi.net-web site for information on CRRT
AKIN.org
Crrtonline.com-web site for info on Dr Mehta’s meeting
www.PCRRT.com Pediatric CRRT with links to other
meetings, protocols, industry
 PCRRT list serve (contact Tim Bunchman)
Brophy University of Iowa
Thanks
 ppCRRT members
 Bedside ICU and Dialysis Nurses
 patients
Brophy University of Iowa