Anticoagulation in CRRT

Timothy E. BunchmanProfessor

Pediatric Nephrology & Transplantation

Anti-Coagulation What is best? Can you run anticoagulation free?

Having no anticoagulation shortens circuit life Will you use Heparin?

Patient bleeding Platelet count (HIT)

Will you use Citrate? Citrate lock Metabolic alkalosis

Anticoagulation free Protocols Classically occur in patients with MODS

with abnormal clotting parameters Usually these patient are given ample

amount of platelet infusions and coagulation factors

This excessive amount of volume adds to greater need for ultrafiltration

Final affect is clotting

Mehta,RL. Regional Citrate anticoagulation for CAVHD in critically ill patients . Kidney Int, 38; 976-978, 1990.

Filter Life (hours)

CitrateHeparin

Saline Flushes

Heparin or Citrate(Mehta data)

Heparin ProtocolsBenefit 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

Citrate: How does it work Clotting is a calcium dependent

mechanism; chelating calcium within 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

Citrate: Mechanism of Action (Thanks to Peter Skippen)

Relationship of Prefilter [Citrate] to Prefilter iCa

0

0.2

0.4

0.6

0.8

1

1.2

0 1 2 3 4 5 6 7 8

Prefilter [Citrate] mmol/L

Prefilter iCa mmol/L

Citrate: Advantages

No need for heparin Commercially available

solutions exist (ACD-citrate-Baxter)

Less bleeding risk Simple to monitor Many protocols exist

(Citrate = 1.5 x BFR150 mls/hr)

(Ca = 0.4 x citrate rate60 mls/hr)

Normocarb Dialysate

Normal Saline Replacement Fluid

Calcium can be infused in 3rd lumen of triple lumen access if available.

(BFR = 100 mls/min)

ACD-A/Normocarb Wt range 2.8 kg – 115 kgAverage life of circuit on citrate 72 hrs (range 24-143 hrs)

Pediatr Neph 2002, 17:150-154

Complications of Citrate:Metabolic alkalosis

Metabolic alkalosis due to citrate converts to HCO3 (1 mmol of citrate

converts to 3 mmols of HCO3)-major cause Solutions contain 35 meq/l HCO3-minor

cause NG losses-minor cause TPN with acetate component-minor cause

Rx metabolic alkalosis by addition of an acid load = Normal Saline (pH 5.4)

Complications of Citrate:“Citrate Lock”

Seen with rising total calcium with either a sustained or dropping patient ionized calcium Essentially delivery of citrate exceeds hepatic

metabolism and CRRT clearance Rx of “citrate lock”

Decrease or stop citrate for 10-30 minutes then restart at 70% of prior rate

Patients receiving multiple blood products receive additional citrate that may not be accounted for!

What is the best anticoagulant

None Heparin

Standard Low molecular weight

Citrate

Citrate Heparin LM Hep

Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.Hoffbauer R et al. Kidney Int. 1999;56:1578-1583.

Heparin circuits 13 patients with 45 filters 29.4 + 23 hrs average length of circuit

Citrate circuits 16 patients with 51 filters 49.1 + 26 hrs average length of circuit

(p < 0.001)

Heparin or Citrate?(M Golberg RN et al, Edmonton PCRRT 2002)

Filter clot free survival at fixed time intervals according to method of anticoagulation

0. 00

0. 25

0. 50

0. 75

1. 00

Ti me f r om st ar t of CRRT ( hour s)

0 20 40 60 80 100 120

Ci t r at e Hepar i n

(data from Sheldon Tobe)

citrate

heparin

ppCRRT- AnticoagulationCenter, Patient and Circuit Demographics Data collected from 1/1/01 through 10/31/03 HepACG only: 3 centers (1 CVVH, 2 CVVHD) CitACG only: 2 centers HepACG changed to CitACG: 2 centers

138 patients total

18208 hours of CRRT circuit time 230 hepACG circuits (52%) (9468.hrs) 158 citACG circuits (36%) (6545 hrs) 54 noACGcircuits (12%) (2185 hrs)

ppCRRT: Anticoagulation

Hep

Cit

No

Cumulative Proportion Surviving (Kaplan-Meier)

Complete Censored

Circuit Survival Time (hours)

Cu

mu

lative

Pro

po

rtio

n S

urv

ivin

g

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

0 20 40 60 80 100 120 140 160 180 200 220

(Brophy et al, submitted)

ppCRRT: Anticoagulation 43/158 citACG vs 58/230 hepACG clotted (NS) 9 pts (hepACG) had systemic bleeding; 4 led to

hepACG discontinuation 1 pt (hepACG) developed Thrombocytopenia

leading to hepACG discontinuation No systemic bleeding side effects were reported

with citACG; 4 pts developed alkalosis and 2 pts with hepatic failure developed citrate lock.

No correlation between circuit survival and (1) mean hepACG rate (2) #ACT/hour or (3) # ACT’s less 180 seconds

Summary Many protocols exist for anticoagulation All have risk and benefit Heparin with protamine has been used

but adds to potential complications and work at bedside

Conclusion Choice of anticoagulation is best decided

locally For the benefit of the bedside staff who do

the work come to consensus and use just one protocol

Having the “protocol” changed per whim of the physician does not add to the the care of the child but subtracts due to additional confusion and work at bedside