Anticoagulation in CRRT Timothy E. Bunchman Professor 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 Heparin or Citrate (Mehta data) Saline Flushes Filter Life (hours) Citrate Heparin Mehta,RL. Regional Citrate anticoagulation for CAVHD in critically ill patients . Kidney Int, 38; 976-978, 1990.

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

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) Citrate as CPD is the anticoagulant used to collect and store blood for transfusion. Every bloodbank to my knowledge uses it. IT WORKS! As you can see from this slide, the effects of citrate on the ionized calcium levels in the blood are dose related. The body easily handles the citrate load by metabolism, particularly in the liver, but virtually everywhere as a substrate for the citric acid cycle (Krebs Cycle).

Citrate: Advantages No need for heparin Commercially available solutions exist (ACD-citrate-Baxter) Less bleeding risk Simple to monitor Many protocols exist

ACD-A/Normocarb Wt range 2.8 kg – 115 kg (Ca = 0.4 x citrate rate 60 mls/hr) (Citrate = 1.5 x BFR 150 mls/hr) Pediatr Neph 2002, 17:150-154 (BFR = 100 mls/min) Normal Saline Replacement Fluid Calcium can be infused in 3rd lumen of triple lumen access if available. Normocarb Dialysate ACD-A/Normocarb Wt range 2.8 kg – 115 kg Average life of circuit on citrate 72 hrs (range 24-143 hrs)

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.

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

Filter clot free survival at fixed time intervals according to method of anticoagulation citrate heparin (data from Sheldon Tobe)

ppCRRT- Anticoagulation Center, 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 (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