Abstract

IntroductionLiver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. The aim of this study was to investigate the predictive capability of baseline liver function parameters regarding citrate accumulation, expressed as an increase in the calcium total/calcium ionized (Catot/Caion) ratio ≥2.5, and to describe the feasibility of citrate CVVHD in liver failure patients.MethodsWe conducted a prospective observational study in medical ICU patients treated in a German university hospital. We performed 43 CVVHD runs using citrate for regional anticoagulation in 28 critically ill patients with decompensated liver cirrhosis or acute liver failure (maximum of two CVVHD runs per patient). Liver function was characterized before CVVHD using laboratory parameters, calculation of Child-Pugh and Model of End-stage Liver Disease scores, and determination of the plasma disappearance rate of indocyanine green. In addition to blood gas analysis, we measured total calcium and citrate in serum at baseline and after definitive time points for each CVVHD run.ResultsAccumulation of citrate in serum correlated with an increase in the Catot/Caion ratio. Although the critical upper threshold of Catot/Caion ratio ≥2.5 was exceeded 10 times in seven different CVVHD runs, equalization of initial metabolic acidosis was possible without major disturbances of acid-base and electrolyte status. Standard laboratory liver function parameters showed poor predictive capabilities regarding citrate accumulation in terms of an elevated Catot/Caion ratio ≥2.5. In contrast, serum lactate ≥3.4 mmol/l and prothrombin time ≤26% predicted an increase in the Catot/Caion ratio ≥2.5 with high sensitivity (86% for both lactate and prothrombin time) and specificity (86% for lactate, 92% for prothrombin time).ConclusionsDespite substantial accumulation of citrate in serum, CVVHD with regional citrate anticoagulation seems feasible in patients with severely impaired liver function. Citrate accumulation in serum is reflected by an increase in the Catot/Caion ratio. To identify patients at risk for citrate accumulation in terms of a Catot/Caion ratio ≥2.5, baseline serum lactate (threshold ≥3.4 mmol/l) and prothrombin time (threshold ≤26%) may be useful for risk prediction in daily clinical practice. Careful monitoring of electrolytes and acid-base status is mandatory to ensure patient safety.

Highlights

  • Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation

  • A correlation between citrate in serum and the total calcium (Catot)/ionized calcium (Caion) ratio in critically ill patients without liver failure has previously been described by Hetzel and colleagues [24]. We demonstrate this relationship between serum citrate levels and the Catot/Caion ratio in liver failure patients

  • We identified a prothrombin time ≤26% and a serum lactate level ≥3.4 mmol/l to be useful for predicting citrate accumulation

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Summary

Introduction

Liver failure patients might be at risk for citrate accumulation during continuous venovenous hemodialysis (CVVHD) with regional citrate anticoagulation. Citrate metabolism is impaired with the risk of citrate accumulation [10] This impairment can result in a drop of Caion due to complex binding between citrate and Caion requiring more calcium chloride substitution at the venous line of the extracorporeal circuit. This binding leads to an increase in the concentration of total calcium (Catot), defined as the sum of Caion, protein, and citrate-bound calcium. Metabolic acidosis with an enlarged anion gap due to reduced citric acid cycle production of bicarbonate out of citrate and accumulation of negative loaded citrate ions might be observed as a complication of CVVHD using citrate for regional anticoagulation [12]

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