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Brophy University of Iowa
Pediatric CRRT Anticoagulation
Patrick Brophy MDDirector Pediatric NephrologyUniversity of Iowa- Children’s HospitalPCRRT Orlando June 2008
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Brophy University of Iowa
Objectives
Review rationale for anticoagulation Options Heparin/citrate Available data
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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
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Brophy University of Iowa
Optimal Anticoagulation
Should be: Readily available Consistently delivered (protocols) Safe!!!! Easily monitored Commercially available Be associated with minimal side effects
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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
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Brophy University of Iowa
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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
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Brophy University of Iowa
Heparin
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Brophy University of Iowa
Heparin UnFrac
LowMW Hep
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Brophy University of Iowa
LMWH: Theoretic advantages
Reduced risk of bleeding Less risk of HIT
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Brophy University of Iowa
LMWH
No difference in risk of bleeding
No quick antidote Increased cost No difference in filter life
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Brophy University of Iowa
Heparin Protocols Heparin infusion prior to filter with post
filter ACT measurement and heparin adjustment based upon parameters
Bolus with 10-20 units/kg Infuse heparin at 10-20 units/kg/hr Adjust post filter ACT 180-200 secs Interval of checking is local standard and
varies from 1-4 hr increments
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Brophy University of Iowa
Heparin Protocols Benefit and Risks
BenefitsBenefits Heparin infusion
prior to filter with post filter ACT measurement
Bolus with 10-20 units/kg Infuse at 10-20 units/kg/hr
Adjust post filter ACT 180-200 secs
RisksRisks Patient Bleeding Unable to inhibit
clot bound thrombin
Ongoing thrombin generation
Activates - damages platelets /thrombocytopenia
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Brophy University of Iowa
Citrate
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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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Brophy University of Iowa
CITRATE
CalciumDependentPathways
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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
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Brophy University of Iowa
(Citrate = 1.5 x BFR150 mls/hr)
(Ca = 0.4 x citrate rate60 mls/hr) (8mg/ml)
Dialysate
Replacement Fluid
Calcium can be infused in 3rd lumen of triple lumen access if available.
(BFR = 100 mls/min)
Pediatr Neph 2002, 17:150-154
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Brophy University of Iowa
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
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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
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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
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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
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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
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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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Brophy University of Iowa
Citrate or Heparin: literature
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Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.
Citrate Unfractionated Heparin
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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
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Brophy University of Iowa
Heparin or Citrate?.
single center - 209 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.
Morgera S, et.al. Nephron Clin Pract. 2004; 97(4):c131-6.
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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
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Brophy University of Iowa
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Brophy University of Iowa
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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
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Brophy University of Iowa
Anticoagulation and CRRT
Heparin and citrate anticoagulation most commonly used methods
Heparin: bleeding risk Citrate: alkalosis, citrate lock
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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 www.PCRRT.com Pediatric CRRT with
links to other meetings, protocols, industry
PCRRT list serve (contact Tim Bunchman)
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Brophy University of Iowa
Thanks
ppCRRT members Bedside ICU and Dialysis Nurses Mary Lee Neuberger/Rhonda Cass patients