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ANTICOAGULATION PCRRT 2008 Orlando

This article discusses the use of heparin and citrate as anticoagulants in pediatric and adult patients undergoing PCRRT. It explores the benefits, risks, and protocols associated with each option.

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ANTICOAGULATION PCRRT 2008 Orlando

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  1. ANTICOAGULATIONPCRRT 2008 Orlando Patrick Brophy MD Director Pediatric Nephrology University of Iowa- Children’s Hospital

  2. Normal Coagulation Tissue Factor (extrinsic) TF:VIIa Contact Phase (intrinsic) XII activation XI IX platelets / monocytes / macrophages X Xa Va VIIIa Ca++ platelets prothrombin THROMBIN fibrinogen CLOT

  3. Sites of Thrombus Formation • Any blood surface interface • Hemofilter • Bubble trap • Catheter (Especially Pediatrics) • Areas of turbulence resistance • Luer lock connections / 3 way stopcocks

  4. 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

  5. Heparin

  6. Sites of Action of Heparin Contact Phase (intrinsic) XII activation XI IX Tissue Factor (extrinsic) TF:VIIa platelets / monocytes / macrophages X Xa Va VIIIa Ca++ platelets LMWH UF HEPARIN prothrombin THROMBIN fibrinogen CLOT

  7. LMWH: Theoretic advantages • Reduced risk of bleeding • Less risk of HIT

  8. LMWH • No difference in risk of bleeding • No quick antidote • Increased cost • No difference in filter life

  9. 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

  10. 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 Heparin Protocols Benefit and Risks

  11. Citrate

  12. Ca++ Ca++ Ca++ Ca++ Ca++ Ca++ Sites of Action of Citrate TISSUE FACTOR TF:VIIa CONTACT PHASE XII activation XI IX monocyte/ platelets / macrophage X Va VIIIa Ca++ platelets Xa Phospholipid surface prothrombin CITRATE THROMBIN NATURAL ANTICOAGULANT (APC, ATIII) FIBRINOLYSIS ACTIVATION FIBRINOLYSIS INHIBITION fibrinogen CLOT

  13. 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

  14. 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

  15. 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

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

  17. 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

  18. Citrate: Problems • Metabolic alkalosis • Metabolized in liver / other tissues • Electrolyte disorders • Hypernatremia • Hypocalcemia • Hypomagnesemia • Cardiac toxicity • Neonatal hearts

  19. 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) to allow for the total solution exposure to be identical (ie no change in solute clearance) yet this will give less HCO3 exposure and an acid replacement NG losses Replace with ½-2/3 NS TPN with acetate component Use high Cl ratio Complications of Citrate:Metabolic alkalosis

  20. 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

  21. Citrate or Heparin: literature

  22. Hoffbauer R et al. Kidney Int. 1999;56:1578-1583. Unfractionated Heparin Citrate

  23. 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

  24. 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 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.

  25. Brophy et.al. NDT 2005 Jul;20(7):1416-21 Comparison of CRRT circuit life for PRISMA circuits with: no anticoagulation (filled squares), heparin anticoagulation (filled circles) or citrate anticoagulation (filled triangles). Mean circuit survival was no different for circuits receiving hepACG and citACG but was significantly lower for circuits with noACG (P<0.005).

  26. 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

  27. Reference Tools • Adqi.net-web site for information on CRRT • Crrtonline.com-web site for info on Dr Mehta’s meeting • www.PCRRT.com Pediatric CRRT with links to other meetings, protocols, industry • 5th International Conf on Pediatric CRRT June 19-21, 2008 Orlando, Florida • PCRRT list serve (contact Bunchman)

  28. Thanks • ppCRRT members • Bedside ICU and Dialysis Nurses • Mary Lee Neuberger • Dr. Noel Gibney (for the slide master) • patients

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