Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study.

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Abstract

Regional citrate anticoagulation (RCA) for continuous renal replacement therapy is widely used in intensive care units (ICUs). However, concern exists about the safety of citrate in patients with liver failure (LF). The aim of this study was to evaluate safety and efficacy of RCA in ICU patients with varying degrees of impaired liver function.

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Citrate anticoagulation for continuous venovenous hemofiltration.

Heleen Oudemans-van Straaten, Rob J Bosman, Matty Koopmans … (2009)

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.

Mehran Monchi, Denis Berghmans, Didier Ledoux … (2004)

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.

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Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.

Demetrios J Kutsogiannis, R T Noel Gibney, Daniel E Stollery … (2005)

We determined the effect of regional citrate versus systemic heparin anticoagulation for continuous renal replacement therapy in critically ill subjects suffering from acute renal failure who were not at high risk for hemorrhagic complications. Between April 1999 and June 2002, 30 critically ill subjects requiring continuous renal replacement therapy and using 79 hemofilters were randomly assigned to receive regional citrate or systemic heparin anticoagulation. The median hemofilter survival time was 124.5 hours (95% CI 95.3 to 157.4) in the citrate group, which was significantly longer than the 38.3 hours (95% CI 24.8 to 61.9) in the heparin group (P < 0.001). Increasing illness severity score, male gender, and decreasing antithrombin-III levels were independent predictors of an increased relative hazard of hemofilter failure. After adjustment for illness severity, antithrombin-III levels increased significantly more over the period of study in the citrate as compared to the heparin group (P= 0.038). Moreover, after adjustment for antithrombin-III levels and illness severity score, the relative risk of hemorrhage with citrate anticoagulation was significantly lower than that with heparin (relative risk of 0.14; 95% CI 0.02 to 0.96, P= 0.05). Compared with systemic heparin anticoagulation, regional citrate anticoagulation significantly increases hemofilter survival time, and significantly decreases bleeding risk in critically ill patients suffering from acute renal failure and requiring continuous renal replacement therapy.

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Journal

Journal ID (iso-abbrev): Crit Care

Title: Critical care (London, England)

Publisher: Springer Nature

ISSN (Electronic): 1466-609X

ISSN (Print): 1364-8535

Publication date (Electronic): Sep 29 2015

Volume: 19

Affiliations

[1 ] Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. torsten.slowinski@charite.de.

[2 ] Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. stanislao.morgera@charite.de.

[3 ] Divison of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria. michael.joannidis@i-med.ac.at.

[4 ] Department of Visceral and Transplant Surgery, University Hospital Charité, CVK, Berlin, Germany. thomas.henneberg@charite.de.

[5 ] Surgical Intensive Care, University Hospital Zurich, Zurich, Switzerland. reto.stocker@hirslanden.ch.

[6 ] Department of Anesthesiology, Oslo University Hospital, Oslo, Norway. ehj@ous-hf.no.

[7 ] Department of Acute Medicine, Oslo University Hospital, Oslo, Norway. kide@uus.no.

[8 ] Department of Anesthesiology, Leipzig University Hospital, Leipzig, Germany. markus.wehner@kh-mtl.de.

[9 ] Clinical Research, Fresenius Medical Care, Bad Homburg, Germany. justyna.kozik-jaromin@fmc-ag.com.

[10 ] Department of Anesthesiology, University Hospital Duesseldorf, Heinrich-Heine-University, Duesseldorf, Germany. brett@uni-duesseldorf.de.

[11 ] Divison of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Innsbruck, Austria. julia.hasslacher@i-med.ac.at.

[12 ] Surgical Intensive Care, University Hospital Zurich, Zurich, Switzerland. john.stover@fresenius-kabi.com.

[13 ] Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. harm.peters@charite.de.

[14 ] Department of Nephrology, University Hospital Charité, Campus Mitte (CCM), Charitéplatz 1, D-10117, Berlin, Germany. hans-h.neumayer@charite.de.

[15 ] Department of Anesthesiology, University Hospital Duesseldorf, Heinrich-Heine-University, Duesseldorf, Germany. kindgen-milles@med.uni-duesseldorf.de.

Article

Publisher Item ID: 10.1186/s13054-015-1066-7

DOI: 10.1186/s13054-015-1066-7

PMC ID: 4587580

PubMed ID: 26415638

SO-VID: fb7956eb-59f3-4628-abe7-5e121b5ab1f5

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Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study.

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Most cited references 26

Citrate anticoagulation for continuous venovenous hemofiltration.

Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study.

Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients.

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