Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury

Abstract

Introduction: Regional citrate anticoagulation (RCA) is gaining popularity in continous renal replacement therapy (CRRT) for critically ill patients. The risk of citrate toxicity is a primary concern during the prolonged process. The aim of this study was to assess the pharmacokinetics of citrate in critically ill patients with AKI, and used the kinetic parameters to predict the risk of citrate accumulation in this population group undergoing continuous veno-venous hemofiltration (CVVH) with RCA.

Methods: Critically ill patients with AKI (n = 12) and healthy volunteers (n = 12) were investigated during infusing comparative dosage of citrate. Serial blood samples were taken before, during 120 min and up to 120 min after infusion. Citrate pharmacokinetics were calculated and compared between groups. Then the estimated kinetic parameters were applied to the citrate kinetic equation for validation in other ten patients' CVVH sessions with citrate anticoagulation.

Results: Total body clearance of citrate was similar in critically ill patients with AKI and healthy volunteers (648.04±347.00 L/min versus 686.64±353.60 L/min; P = 0.624). Basal and peak citrate concentrations were similar in both groups (p = 0.423 and 0.247, respectively). The predicted citrate curve showed excellent fit to the measurements.

Conclusions: Citrate clearance is not impaired in critically ill patients with AKI in the absence of severe liver dysfunction. Citrate pharmacokinetic data can provide a basis for the clinical use of predicting the risk of citrate accumulation.

Trial registration: ClinicalTrials.gov Identifier NCT00948558.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Plasma citrate concentrations (mean ± SD) during 120 min citrate infusion and 120 min after the end of citrate infusion in critically ill patients with AKI (n = 12) and in healthy volunteers (n = 12).

Figure 2. Measured citrate and ionized calcium curves during the first 8 hours of CVVH using citrate anticoagulation while the blood rate were set at 150–200 ml/min and the substitution fluid were at the rate of 4 L/h (n = 10 treatments).

Figure 3. The mean measured and predicted systemic citrate concentrations with 95% confidence intervals at 1 h, 3 h, 6 h and 8 h (vertical lines).

Figure 4. Comparison of predicted and measured systemic citrate concentrations at the 3rd hour (upper) and 8th hour (lower) of CVVH with RCA.

The dotted lines represented the 95% confidence intervals of the differences of predicted and measured systemic citrate concentrations.