Anticoagulation in CVVH

(peds)
Patrick Brophy MD
Director Pediatric Nephrology
University of Iowa- Childrens Hospital
PCRRT Rome 2010

Brophy University of Iowa

Objectives

Review rationale for anticoagulation

Options
Heparin/citrate
Available data

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Relevance to CRRT

Functional circuit life is imperative

to:
Dose

delivery
Staff statisfaction
Patient morbidity (changing lines)
Cost of therapymulti circuit use

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Optimal Anticoagulation

Should be:
Readily

available
Consistently delivered (protocols)
Safe!!!!
Easily monitored
Commercially available
Be associated with minimal side effects

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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

Sites of Thrombus Formation

Any blood
surface
interface

Hemofilter
Bubble trap
Catheter
(Especially
Pediatrics)

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Areas of
turbulence
resistance
Luer lock
connections / 3
way stopcocks

Heparin

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Heparin UnFrac
LowMW Hep

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LMWH: Theoretic advantages

Reduced risk of bleeding

Less risk of HIT

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LMWH
No

difference in risk of
bleeding
No quick antidote
Increased cost
No difference in filter life

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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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Heparin Protocols Benefit and Risks

Benefits
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

Risks
Patient Bleeding
Unable to inhibit
clot bound
thrombin
Ongoing thrombin
generation
Activates - damages
platelets
/thrombocytopenia

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Citrate

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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
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(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)

Dialysate

Replacement
Fluid

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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

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Citrate: Advantages

No need for heparin

Commercially available
solutions exist (ACD-citrateBaxter)
Less bleeding risk
Simple to monitor
Many protocols exist

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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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Citrate: Problems

Metabolic alkalosis

Electrolyte disorders

Metabolized in liver / other tissues

May be associated with post CRRT raclcitrant
hypercalcemia
Hypernatremia
Hypocalcemia
Hypomagnesemia

Cardiac toxicity

Neonatal hearts
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Complications of Citrate:
Metabolic alkalosis

Metabolic alkalosis due

to

Treatment

citrate conversion to
HCO3
Solutions with 35 meq/l
HCO3
NG losses
TPN with acetate
component

Solutions with 35 meq/l

HCO3

NG losses

Replace with -2/3

NS

TPN with acetate

component

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Decrease bicarbonate
dialysis rate and
replace at the same
rate with NS (pH 5)

Use high Cl ratio

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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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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Heparin or Citrate?
.
Morgera
S, et.al. Nephron Clin Pract. 2004; 97(4):c131-6.

single center - 209 adults

regional anticoagulation : trisodium citrate vs
standard heparin protocol ( customized calciumfree 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.
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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

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

cases of citrate lock

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Anticoagulation and CRRT

Heparin and citrate anticoagulation

most commonly used methods
Heparin: bleeding risk
Citrate: alkalosis, citrate lock

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Reference Tools

Adqi.net-web site for information on

CRRT
AKIN.org
Crrtonline.com-web site for info on Dr
Mehtas meeting
www.PCRRT.com Pediatric CRRT with
links to other meetings, protocols,
industry
PCRRT list serve (contact Tim Bunchman)

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Thanks

ppCRRT members
Bedside ICU and Dialysis Nurses
Mary Lee Neuberger/Rhonda Cass
patients

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