Brophy-Citrate - Pediatric Continuous Renal Replacement

Citrate Anticoagulation
Patrick Brophy MD, MHCDS
Professor & Director Pediatric
University of Iowa- Children’s Hospital
London 2015
Brophy University of Iowa
 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
 Saline Flushes
 Heparin Peds
 Citrate regional
anticoagulation Peds
 Low molecular weight
 Prostacyclin
 Nafamostat mesilate
 Danaparoid*
 Hirudin/Lepirudin
 Argatroban (thrombin
* No antidote known
Brophy University of
Brophy University of Iowa
Sites of Thrombus Formation
Any blood surface
 Hemofilter
 Bubble trap
 Catheter (Especially
 Areas of turbulence
 Luer lock
connections / 3 way
Brophy University of Iowa
Brophy University of Iowa
How does citrate work
 Clotting is a calcium dependent mechanism,
removal of calcium from the blood will inhibit
 Adding citrate to blood will bind the free calcium
(ionized) calcium in the blood thus inhibiting
 Common example of this is blood banked blood
Brophy University of Iowa
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
(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)
Brophy University of Iowa
Calcium can be infused in 3rd
lumen of triple lumen access if
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
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
 NG losses
 TPN with acetate
 Treatment
 Solutions with 35 meq/l
 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
 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
Brophy University of Iowa
Citrate or Heparin: literature
Brophy University of Iowa
Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Unfractionated Heparin
Brophy University of
 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
- 209Nephron
adults Clin Pract. 2004; 97(4):c131-6.
 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
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
 site for information on CRRT site for info on Dr Mehta’s meeting Pediatric CRRT with links to other
meetings, protocols, industry
 PCRRT list serve (contact Tim Bunchman)
Brophy University of Iowa
 ppCRRT members
 Bedside ICU and Dialysis Nurses
 patients
Brophy University of Iowa