Citrate Pharmacokinetics in Critically Ill Patients with Acute Kidney Injury

Abstract

IntroductionRegional 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.MethodsCritically 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.ResultsTotal 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.ConclusionsCitrate 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 RegistrationClinicalTrials.gov Identifier NCT00948558

Regional Citrate Anticoagulation for RRTs in Critically Ill Patients with AKI

“…Thus, the final whole-body citrate balance, which is the main determinant of systemic citrate levels, results from the difference between the citrate load and metabolic disposal. Although the metabolic clearance of citrate is reduced and the half-life is prolonged in patients with liver disease (40), no major differences in citrate kinetics have been documented in patients with AKI compared with subjects with normal renal function (41). The ensuing bicarbonate production from citrate metabolism along with bicarbonate in replacement/dialysis fluids provides the buffer supply to the patient.…”

Optimized Calcium Supplementation Approach for Regional Citrate Anticoagulation

“…As demonstrated in our previous study [13,14], there was a "2-phase" phenomenon in the calcium supplementation approach during RCA-CRRT; however, this approach was complicated and lacked the convenience and universality for use during other modalities of RCA-CRRT. The amount of calcium supplementation in the first phase depends on the calcium loss into the effluent and the calcium chelated by citrate.…”

“…A "2-phase" phenomenon of calcium supplementation during continuous veno-venous hemofiltration (CVVH) with RCA (RCA-CVVH) was observed and demonstrated in our previous study, which was based on the pharmacokinetics and extracorporeal removal of citrate and calcium [13,14]. The calcium supplementation can be expressed as follows:…”

“…The aforementioned effluent calcium loss has been verified only in RCA-CVVH using complicated mathematical parameters, and it lacks convenience and universality in other modalities [13,14]. Therefore, the present study aimed to optimize the effluent calcium loss supplementation approach using the extracorporeal removal characteristics of calcium.…”

Risks and benefits of citrate anticoagulation for continuous renal replacement therapy

“…22 However, reduced metabolism of citrate occurs in patients with chronic liver disease, ischaemic hepatitis, hypoxia and impaired muscle perfusion, which are commonly found in the ICU setting. Citrate accumulation results in ionised hypocalcaemia and acidosis, which cause hypotension due to decreased myocardial contractility and vascular hypotonia.…”