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Blood epuration of middle molecules in continuous venovenous hemodiafiltration with regional citrate anticoagulation versus systemic heparinization


Adequate anticoagulation is a precondition to improve blood epuration. In a prospective crossover trial, we compared the removal of middle molecules in continuous renal replacement therapy, by two methods that used either trisodium citrate ACD (BRAUN Laboratories) or heparin as anticoagulation.


Fourteen critically ill patients were treated by continuous venovenous hemodiafiltration. The dialysate and hemofiltration flows were 1,500 ml/hour each. All patients received two sessions of 36 hours successively. Patients 1 to 7 received systemic heparinization first, then regional anticoagulation by citrate. Conversely, Patients 8 to 14 received heparin and then citrate. Every 12 hours during each session of renal replacement (T0, T12, T24 and T36), blood epuration of small molecules (urea, creatinine) and middle molecules (β2-microglobulin, retinol binding protein) were evaluated from blood and effluent samples.


At all time periods, there was no significant difference in creatinine and urea clearances between citrate and heparin treatment, except in T12 where creatinine clearance was significantly higher when using citrate than when using heparin (38.5 ± 4.0 ml/min vs. 34 ± 4.1 ml/min, P = 0.02). We did not observe a significant decline of urea and creatinine clearance during the session. The retinol binding protein blood and effluent rates were limited and stable during the session. Between T0 and T12, results showed a significant improvement of β2-microglobulin clearance with using citrate or heparin. After T12, β2-microglobulin clearance decreased with citrate treatment and stayed stable with heparin. Clearance seems to be higher with citrate than heparin, however, with only a significant difference in T12 (20.1 ± 4.0 vs. 16.3 ± 3.1 ml/min, P = 0.02). Undergoing citrate treatment, we recorded significant metabolic alkalosis (P = 0.0025) but without hypernatremia.


Regional citrate anticoagulation in continuous venovenous hemodiafiltration is an efficient and safe method of anticoagulation. Its impact upon blood epuration of small or middle molecules remains to be established.

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Nogier, M., Lavayssiere, L., Cointault, O. et al. Blood epuration of middle molecules in continuous venovenous hemodiafiltration with regional citrate anticoagulation versus systemic heparinization. Crit Care 13 (Suppl 1), P270 (2009).

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  • Heparin
  • Creatinine Clearance
  • Renal Replacement Therapy
  • Continuous Renal Replacement Therapy
  • Trisodium