Regional Citrate Anticoagulation (RCA) in CRRT,Dr Anne Leung QEH ICU 2010,Overview,Mechanism of action and metabolism of citrateFormulation of citrate Advantage and disadvantage of using citrate anticoagulantRCA CRRT circuit options Gambro vs Fresenius Monitoring during citrate anticoagulationQEH ICU Citrate anticoagulation regime,CRRT circuit,Vascular accessBlood FlowMachineryDialyzerCircuit volumeDialysate/Replacement fluidAnticoagulant,Anticoagulation for CRRT,CRRT increasing in popularity in management of acute renal failure in critically ill Need ongoing anticoagulationRisk of bleeding with heparin 2% per day 3.5-10% of deaths 25% of new hemorrhagic episodes,CRRT,Clotting,Bleeding,Contact activation by membrane,1,2,Impact of filter clotting,Decrease in dialysis doseBlood loss through the circuit with increase in transfusion requirementWasted nursing timeIncrease in cost,Anticoagulation options,None (- if marked coagulopathy) Unfractionated heparin LMW Heparin Citrate Direct Thrombin Inhibitors r-Hirudin Argatroban Prostacycline,Continuous renal replacement therapy: B.E.S.T. Kidney (The Beginning and Ending Supportive Therapy for the kidney). a worldwide practice survey. 23 Countries, 54 ICUs, 1006 patients with ARF on CRRT,Intensive Care Med. 2007;33(9):1563-70,Mechanism of Regional Citrate Anticoagulant,Normal range: Total serum calcium: 2.2-2.6 mmol/L Serum ionized calcium: 0.9 -1.2 mmol/LChelate Ca and induce deep hypoclacemia in filter Aim post-filter iCa of 0.25-0.35 mmol/lFate of the citrate-calcium complex in the CRRT circuit Partly lost in ultrafiltrate across the membrane Those enter the systemic circulation is diluted in venous blood Citrate entering the body will be cleared by liver, skeletal muscle or kidney to HCO3 in 1:3 ratio Half-life of calcium-citrate complex is 5 minutes, therefore systemic effect on anticoagulation not occurred,Fate of the citrate calcium complex in the CRRT circuit,What is the citrate dose required?,To achieve a steady state whole blood citrate conc. of 4 mmol/L,Flanigan MJ et al. Am J kid Dis 1996:27 (4) 519-524,Citrate dose,Citrate dose = 240/60( ml/min) x 113 / 160 = 2.83 mmol/L,Citrate Formulation,Trisodium Citrate 4% Na 420. Citrate 136.Acid Citrate Dextrose (ACD-A) Dextrose 2.45% Citric acid 0.8% (38 mmol/L). Trisodium Citrate 2.2% (74.8mmol/L), Na 224. Citrate 113.Gambro Prismocitrate 10/2 Fresenius multifiltrate Ci-Ca system,Difference between TSC and ACDA,Each millimole of TSC yields 3 mmol/L NaHCO3At physiological pH of 7.4, each millimole of citric acid combines with 3 mmol/L NaHCO3 and converted to TSC or Na citrateFor equimolar infusion of ACD and TSC, ACD produces 203 mmol/L NaHCO3 instead of 320 by TSC,Complex metabolic consequence of using RCA,Metabolic acidosis or metabolic alkalosis Citrate is both the anticoagulant and buffer Acid-base affect by composition of citrate solution, citrate infusion rate, loss by filtration : amt of citrate in UF varies, hence amt of buffer entering in systemic circulation varies metabolism of citric acid :If liver and muscle skeletal muscle fail to metabolized citrate, bicarbonate not produce and citrate accumulateHypernatremia The tri-sodium citrate (TSC) contains substantial amt of sodiumHypocalcemia Amt of calcium lost in UF, bound to citrate is greater than during HF or HD with heparin Use of calcium free dialysate or replacement fluid to improve the anticoagulation effect of citrate,Citrate - Solutions Requirements,Zero Ca2+ Dialysate and or replacement solution to minimize citrate requirement Low Na+ to counter-act the potential problem of hypernatremiaLow bicarbonate level to decrease bicarbonate loadLow or zero MagnesiumCalcium supplementation to correct patients Ca2+ loss,Advantage of RCA,Effective anticoagulation of the extracorporeal circuit Less Clotting Longer filter lifetimesNo systemic anticoagulation No systemic bleeding risk Less bleeding complications Less transfusion requirement,Less clotting in Hollow Fibers membrane Kid Int 1999,Longer Filter Life,Median time to spontaneous hemofilter failure is 140 hr with citrate vs 45 hr with heparin,Less Bleeding Episode,4 out of 12,9 put of 12,Less Transfusion requirement,Use of citrate CVVH was safer and reduced mortality CCM37:545-552(2009),Hospital mortality 41 vs 57% (p=0.03) 3-month Mortality 45 vs 62% (p=0.02),CCM 37: 545 - 552 ( 2009),Surgical,Sepsis,Higher SOFA,Younger than 73,Disadvantage of RCA,Direct anticoagulation control difficult Need for complex protocol with meticulous calculation and many titration requiredComplex metabolic consequences Metabolic Alkalosis or acidosis Hyper or hyponatremia Calcium and magnesium lossCitrate solution are either customized or hospital pharmacy-formulated ( Zero calcium, low sodium and low or buffer free solution)Labor intensive and close monitoring of electrolyte and acid-base requiredRequiring well-trained nursing staffs and well trained nephrologists,Metabolic complication of RCA CRRT,