Regional Citrate Anticoagulation during CVVH in the Pediatric Intensive Care Unit T Gaillot, V Phan, P Jouvet, F Gauvin, C Litalien

Introduction CVVH is being increasingly utilized for the care of PICU patients Imperative need : Effective anticoagulation to prevent recurrent clotting of the extracorporeal circuit and to achieve efficient and uninterrupted therapy Historically, systemic anticoagulation with heparin  mainstay of anticoagulation for CVVH Limits/contraindications : High risk for bleeding Active bleeding Heparin-induced thrombocytopenia Use of activated Protein C Heparin-induced major bleeding complications can be as high as 50 %.

Introduction Regional citrate anticoagulation (RCA): Attractive alternative to systemic heparinization with less risk of bleeding Citrate chelates ionized Ca2+, an essential cofactor in the clotting cascade Anticoagulation is limited to the extracorporeal circuit by infusing citrate solution into the arterial limb of the circuit Systemic anticoagulation is avoided by restoring ionized Ca2+ in the systemic circulation by infusing Ca2+ solution through a separate central line

Introduction RCA and mean circuit lifetime: Adult studies Monchi et al, 2004: RCA vs heparin: 70 h vs 40 h Dorval et al, 2003: 44  24 h Pediatric studies Chadha et al, 2002: 51  8 h Elhanan et al, 2004: 56  22 h Bunchman et al, 2002: 71  7 h

Introduction RCA and complications: Citrate is metabolized in the liver and produces HCO3- and citric acid  can result in metabolic alkalosis Accumulation of citrate may occur if liver metabolism is impaired  can result in citrate toxicity or "citrate gap"

Objective To evaluate the mean circuit lifetime and metabolic complications of RCA in critically ill children after the introduction of this anticoagulation technique in our PICU

Material and methods Retrospective chart review Children who underwent hemofiltration with RCA from March 2003 to December 2003 were included Mean circuit lifetime (MCL) and reasons for circuit discontinuation were determined Metabolic alkalosis : pH  7.45 and HCO3-  30 mmol/L Citrate gap : total to ionized Ca2+ ratio > 2.5

Calcium chloride (8g/1L NS) Material and methods Normocarb Rate: 2 L/1.73 m2/h Systemic infusion Calcium chloride (8g/1L NS) Rate: 0.4 X ACD-A rate ACD-A Rate: 1.5 X BFR DIALIZER Prisma M-10, M-60 or M-100 (AN-69) From patient To patient BFR: 2-8 ml/kg/min Target post-filter ionized calcium Target patient ionized calcium Ultrafiltrate Normocarb Rate: 2 L/1.73 m2/h Bunchman et al , 2002

27 involuntary discontinuations (73%) MCL= 28  35 h Circuit failure (n=23, 85%)  10 Catheter dysfunction 13 High transmembrane pressure and/or clotting Technical failure (n=3, 11%) 1 impossible auto-test 1 screen failure 1 unknown failure 5 patients mean age 5.5  6.8 y and weight 28.1  33 kg 37 circuits Mean circuit lifetime (MCL) = 29  36 h 10 elective discontinuations (27%) MCL= 29  32 h Medical cause (n=1, 4%) 1 bleeding Age range: Weight range: 3.5 to 85.6 kg Diagnosis : 1 sepsis after cardiac surgery, 1 hemolytic uremic syndrome after bone marrow transplantation and 3 probable ischemic acute tubular necrosis (2 bone marrow transplantations and 1 liver transplantation)

Results Kaplan-Meier curve of time to circuit discontinuation Range Le plus court Le plus long 50 % des circuits

Results Post filter ionized Ca2+ : 0.40  0.10 mmol/L Patient ionized Ca2+ : 1.14  0.13 mmol/L 13 episodes (35 %) of metabolic alkalosis in 4 patients 9 episodes (24 %) of citrate gap in 2 patients 5 children with a mean age of ( ) and a mean weight of 28.133 kg (3.5 to 85.6 kg) Dual-lumen catheters (6.5 to 12 Fr)

Conclusion In our PICU, the mean circuit lifetime using RCA was much shorter than those reported despite post-filter ionized Ca2+ within the optimum range Metabolic alkalosis was frequently encountered Citrate toxicity occurred in 2 patients out of 5 The use of RCA may be somewhat problematic in some critically ill children Optimum range for post-filter ionized Ca2+: In PICU, many factors including immaturity of the newborn liver and SIRS/MODS-related impaired hepatic metabolism, impaired hepatic function, may decrease citrate clearance and multiple transfusions may increase citrate load.

Perspectives RCA remains an attractive option to provide anticoagulation in those patients with heparin contraindications Prospective, randomized controlled trials comparing RCA and systemic heparinization are needed before RCA replaces heparin in all critically ill children The recent introduction of a technique can lead to errors in interpreting a new protocol