Citrate pharmacokinetics at high levels of circuit citratemia during coupled plasma filtration adsorption.

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.

Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients.

BACKGROUND: Citrate anticoagulation is gaining popularity in renal replacement therapies (RRT) for critically ill patients. In order to study whether citrate accumulates in septic shock patients, we determined citrate in plasma and dialysate during continuous venovenous haemodiafiltration (CVVHDF). METHODS: An automated routine determination of citrate was set up using a commercial kit (citrate lyase method). Twelve patients with septic shock on CVVHDF and citrate anticoagulation were studied ex vivo for citrate levels in systemic and circuit blood and in the ultrafiltrate (at 0, 0.5, 1, 3, 6, 9, 12, 24, 48 and 72 h). RESULTS: In vitro blood studies showed a near unit correlation between the plasma measured and predicted citrate concentrations for an exclusive extracellular distribution of citrate. Median systemic arterial citratemias were 0.09 (0.06-0.12) mmol/L (Time 0) and 0.23 (0.18-0.31) mmol/L during treatment; median sieving coefficient for citrate was 0.95 (0.88-1.02) and did not change with different volumes of CVVHDF effluent (from 1350 to 5100 mL/h). Net citrate and calcium removal by filter significantly correlated with effluent volume (r = 0.85 and 0.78, respectively). Median citrate load entering in the patients' bloodstream was 13.60 (9.1-19.6, n = 68) mmol/h. Although cost analysis of the citrate test demonstrated a minimally increased daily cost (from 2.96 to 3.51€), saving costs could be potentially relevant with more extended use of citrate anticoagulation. CONCLUSIONS: In septic shock patients with liver dysfunction citratemia is useful in guiding clinical application of RRT, where the citrate losses in the ultrafiltrate can be efficiently modulated by increasing the effluent volume.

Normal citratemia and metabolic tolerance of citrate anticoagulation for hemodiafiltration in severe septic shock burn patients.

PURPOSE: Anticoagulation during renal replacement therapy remains an important challenge for burn patients due to their high risk of bleeding. In this study we compared the efficacy and safety of citrate anticoagulation to heparin anticoagulation for hemodiafiltration (HDF) in severe burn patients, focusing on metabolic tolerance and handling of citrate. METHODS: Retrospective observational study (January 2000-December 2007) at a university teaching hospital. Among 548 patients admitted with burns, 70 severe burn septic shock patients (median age 57.5 years, interquartile range 42-76 years; median burned surface area 40%, interquartile range 30-60%) who underwent HDF for more than 24 h were included. RESULTS: Of the 70 HDF patients, 31 at high risk of bleeding were treated with citrate and 39 with heparin, with a mortality rate of 70.9 and 71.8%, respectively. In continuous venovenous hemodiafiltration (CVVHDF), the filter survival was higher with citrate, and hemorrhagic complications were lower (0.035 vs. 0.145 episodes/day, respectively). During citrate CVVHDF [median delivered dialysis dose: 578.9 ml kg(-1) day(-1) (461.5-769.2 ml kg(-1) day(-1))] in catecholamine-supported patients (norepinephrine 0.53 µg kg(-1) min(-1)), no metabolic derangements in pH, bicarbonates, Na+, K+, Ca++, and ionized calcium were observed. Systemic citratemia was within the normal range (<0.4 mmol/l) and was associated with a marked citrate removal in the effluent (5 patients, 36-60% of infused amount). CONCLUSIONS: In septic shock burn patients, citrate for CVVHDF was efficient and safe, and superior to heparin for hemorrhagic complications and filter survival. Observed metabolic stability was most likely due to a marked loss of citrate in effluent volume and subsequent low total citrate load for the patient.