title: Citrate pharmacokinetics at high levels of circuit citratemia during coupled plasma filtration adsorption.
abstract: BACKGROUND
  The heparin requirement for coupled plasma filtration adsorption (CPFA) is usually high. Heparin administration often cannot be adherent to prescription, leading to a premature clotting of circuit and an insufficient volume of treated plasma. Regional citrate anticoagulation (RCA) could be an attractive alternative; however, no data are available on citrate pharmacokinetics at high levels of circuit citratemia.
  
  
  METHODS
  Fifteen septic shock patients with acute kidney injury undergoing CPFA with RCA at target circuit citratemia of 6 mmol/L were treated with CPFA-haemofiltration in pure predilution (CPFA-HF predilution group, n = 5 patients), or predilution haemodiafiltration (CPFA-HDF predilution group, n = 5 patients) or pre- and postdilution haemofiltration (CPFA-HF pre/postdilution group, n = 5 patients). Citrate pharmacokinetics was carried out through its determination in systemic and circuit blood, and effluent at time 0, 0.2, 1, 3, 6 and 9 h.
  
  
  RESULTS
  The systemic concentrations of citrate in the CPFA-HF predilution group significantly increased over the sessions (from basal level of 0.21 to 0.76 mmol/L at 3 h), whereas they did not change in CPFA-HDF predilution and CPFA-HF pre/postdilution groups. Circuit plasma citrate concentrations (from 3 to 8 mmol/L) correlated strongly with circuit iCa++ levels (Spearman R = -0.7022, P < 0.01). Sieving coefficients of citrate were near the unit in all three groups and unrelated to blood and infusion flow rates in predilution. However, the amount of citrate removed by effluent was ∼40% for the CPFA-HF predilution group and reached 60% for both the CPFA-HDF predilution and CPFA-HF pre/postdilution groups (P < 0.05). As for the efficiency of plasmafiltration, the plasmafiltrate volume (from 17 to 20 mL/kg/day) was not significantly different among the groups.
  
  
  CONCLUSIONS
  These results demonstrated that in refractory septic shock patients on CPFA at circuit citratemia of 6 mmol/L both HDF predilution and HF pre/postdilution were the best dialysis modalities to maintain a normal systemic citratemia through a high rate of citrate loss in the effluent.
authors: Nefrologia, Dialisi e Trapianto U, Dipartimento di Medicina Generale e Specialistica, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Torino, Italy.
authors: Filippo
authors: F
authors: Mariano
authors: Biochimica Clinica, Dipartimento di Medicina di Laboratorio, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Torino, Italy.
authors: Maurizio
authors: M
authors: Morselli
authors: Nefrologia, Dialisi e Trapianto U, Dipartimento di Medicina Generale e Specialistica, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Torino, Italy.
authors: Zsuzsanna
authors: Z
authors: Holló
authors: Anestesia e Rianimazione 5, Dipartimento di Anestesia e Rianimazione, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Torino, Italy.
authors: Fulvio
authors: F
authors: Agostini
authors: Chirurgia Plastica Grandi Ustionati, Dipartimento di Chirurgia Generale e Specialistica, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Torino, Italy.
authors: Maurizio
authors: M
authors: Stella
authors: Nefrologia, Dialisi e Trapianto U, Dipartimento di Medicina Generale e Specialistica, Citta' della Salute e della Scienza di Torino, Ospedale CTO, Torino, Italy Nefrologia, Dialisi e Trapianto U, Dipartimento di Medicina Generale e Specialistica, Citta' della Salute e della Scienza di Torino, Universita' Degli Studi di Torino, Ospedale CTO, Torino, Italy.
authors: Luigi
authors: L
authors: Biancone
mesh_terms: D058186:Acute Kidney Injury / Q000150:complications* / Q000628:therapy; D000327:Adsorption; D000328:Adult; D000368:Aged; D019343:Citric Acid / Q000493:pharmacokinetics*; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006440:Hemofiltration / Q000379:methods*; D006493:Heparin / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012772:Shock, Septic / Q000209:etiology / Q000628:therapy*; D014018:Tissue Distribution
chemical_list: D019343:Citric Acid; D006493:Heparin
keywords: citrate anticoagulation; citrate concentrations; coupled plasma filtration adsorption; haemodiafiltration; haemofiltration