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      Implementation of continuous renal replacement therapy with regional citrate anticoagulation on a surgical and trauma intensive care unit: impact on clinical and economic aspects—an observational study

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          Regional citrate anticoagulation (RCA) is being increasingly used during continuous renal replacement therapy (CRRT) in intensive care units as an alternative to systemic heparin anticoagulation. However, due to its availability in a variety of solutions and dialysis systems, RCA is still considered a complex intervention, possibly leading to confusion and pitfalls in everyday practice. We therefore tested retrospectively if the introduction of RCA as a new anticoagulation strategy for CRRT was feasible and had not negatively impacted efficacy, safety, metabolic stability, filter lifetime, and cost-effectiveness compared to well-established systemic heparin.


          This observational, retrospective study was performed on a non-cardiac surgical and trauma intensive care unit (ICU) in a university hospital. All charts of patients receiving one of the CRRT techniques from May 2006 to April 2010 were reviewed. The first 60 consecutive patients receiving CRRT with regional citrate anticoagulation after its implementation in February 2008 (continuous veno-venous haemodialysis, Multifiltrate® with integrated CiCa® system, AV 1000 S® filter, n = 60) were included in the study. The last 50 consecutive patients with systemic heparin anticoagulation therapy (continuous veno-venous haemodiafiltration, PRISMAFLEX®, AN69® filter, n = 50), treated immediately before the introduction of RCA, were used as a historic control group.


          Both treatment modalities were effective in terms of uraemia control. Patients in the citrate group presented with significantly higher pH levels, lower ionized calcium levels, and higher sodium levels compared with the heparin treated group, however, without notable adverse clinical events. Interestingly, mean circuit lifetime was significantly longer in the citrate group (48.6 ± 24.2 h vs. 18.8 ± 13.5 h; p < 0.0001). Both treatment modalities were cost-effective.


          Our results suggest that the implementation of regional citrate anticoagulation was safe and effective. Due to the retrospective design of the study and inherent limitations therein concerning several baseline parameters, i.e. different filters, modes of dialysis, and flow parameters not having been standardized, we were unable to draw a causative effect relationship. Nonetheless, our results warrant further study.

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          Most cited references 20

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          Effect of acute renal failure requiring renal replacement therapy on outcome in critically ill patients*

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            Citrate anticoagulation for continuous venovenous hemofiltration.

            Continuous venovenous hemofiltration (CVVH) is applied in critically ill patients with acute renal failure for renal replacement. Heparins used to prevent circuit clotting may cause bleeding. Regional anticoagulation with citrate reduces bleeding, but has metabolic risks. The aim was to compare the safety and efficacy of the two. Randomized, nonblinded, controlled single-center trial. General intensive care unit of a teaching hospital. Adult critically ill patients needing CVVH for acute renal failure and without an increased bleeding risk. Regional anticoagulation with citrate or systemic anticoagulation with the low-molecular weight heparin nadroparin. End points were adverse events necessitating discontinuation of study anticoagulant, transfusion, metabolic and clinical outcomes, and circuit survival. Of the 215 randomized patients, 200 received CVVH per protocol (97 citrate and 103 nadroparin). Adverse events required discontinuation of citrate in two patients (accumulation and clotting) of nadroparin in 20 (bleeding and thrombocytopenia) (p < 0.001). Bleeding occurred in 6 vs. 16 patients (p = 0.08). The median number of red blood cell units transfused per CVVH day was 0.27 (interquartile range, 0.0-0.63) for citrate, 0.36 (interquartile range, 0-0.83) for nadroparin (p = 0.31). Citrate conferred less metabolic alkalosis (p = 0.001) and lower plasma calcium (p < 0.001). Circuit survival was similar. Three-month mortality on intention-to-treat was 48% (citrate) and 63% (nadroparin) (p = 0.03), per protocol 45% and 62% (p = 0.02). Citrate reduced mortality in surgical patients (p = 0.007), sepsis (p = 0.01), higher Sepsis-Related Organ Failure Assessment score (p = 0.006), and lower age (p = 0.009). The efficacy of citrate and nadroparin anticoagulation for CVVH was similar, however, citrate was safer. Unexpectedly, citrate reduced mortality. Less bleeding could only partly explain this benefit, less clotting could not. Post hoc citrate appeared particularly beneficial after surgery, in sepsis and severe multiple organ failure, suggesting interference with inflammation.
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              Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study.

              To compare the efficacy and safety of adjusted-dose unfractionated heparin with that of regional citrate anticoagulation in intensive care patients treated by continuous venovenous hemofiltration (CVVH). Prospective, randomized, clinical trial in a 32-bed medical and surgical ICU in a university teaching hospital. ICU patients with acute renal failure requiring continuous renal replacement therapy, without cirrhosis, severe coagulopathy, or known sensitivity to heparin. Before the first CVVH run patients were randomized to receive anticoagulation with heparin or trisodium citrate. Patients eligible for another CVVH run received the other study medication in a cross-over fashion until the fourth circuit. Forty-nine circuits (hemofilters) were analyzed: 23 with heparin and 26 with citrate. The median lifetime of hemofilters was 70 h (interquartile range 44-140) with citrate anticoagulation and 40 h (17-48) with heparin (p=0.0007). One major bleeding occurred during heparin anticoagulation and one metabolic alkalosis (pH=7.60) was noted with citrate after a protocol violation. Transfusion rates (units of red cells per day of CVVH) were, respectively, 0.2 (0.0-0.4) with citrate and 1.0 (0.0-2.0) with heparin (p=0.0008). Regional citrate anticoagulation seems superior to heparin for the filter lifetime and transfusion requirements in ICU patients treated by continuous renal replacement therapy.

                Author and article information

                0049-731-500-60289 ,
                J Intensive Care
                J Intensive Care
                Journal of Intensive Care
                BioMed Central (London )
                30 July 2015
                30 July 2015
                : 3
                : 1
                [ ]Department of Anaesthesiology, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany
                [ ]Department of Cardioanaesthesiology, Ulm University, Albert-Einstein-Allee 23, 89081 Ulm, Germany
                © Hafner et al. 2015

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

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