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

2. 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 %.

3. 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

4. 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

5. 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"

6. 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

7. 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

8. 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

9. 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)

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

11. 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)

12. 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.

13. 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