Effect of Regional Citrate Anticoagulation vs Systemic Heparin Anticoagulation During Continuous Kidney Replacement Therapy on Dialysis Filter Life Span and Mortality Among Critically Ill Patients With Acute Kidney Injury
JAMA, vol. 324, pp. 1629
Abstract
Importance: Although current guidelines suggest the use of regional citrate anticoagulation (which involves the addition of a citrate solution to the blood before the filter of the extracorporeal dialysis circuit) as first-line treatment for continuous kidney replacement therapy in critically ill patients, the evidence for this recommendation is based on few clinical trials and meta-analyses. Objective: To determine the effect of regional citrate anticoagulation, compared with systemic heparin anticoagulation, on filter life span and mortality. Design, Setting, and Participants: A parallel-group, randomized multicenter clinical trial in 26 centers across Germany was conducted between March 2016 and December 2018 (final date of follow-up, January 21, 2020). The trial was terminated early after 596 critically ill patients with severe acute kidney injury or clinical indications for initiation of kidney replacement therapy had been enrolled. Interventions: Patients were randomized to receive either regional citrate anticoagulation (n = 300), which consisted of a target ionized calcium level of 1.0 to 1.40 mg/dL, or systemic heparin anticoagulation (n = 296), which consisted of a target activated partial thromboplastin time of 45 to 60 seconds, for continuous kidney replacement therapy. Main Outcomes and Measures: Coprimary outcomes were filter life span and 90-day mortality. Secondary end points included bleeding complications and new infections. Results: Among 638 patients randomized, 596 (93.4%) (mean age, 67.5 years; 183 [30.7%] women) completed the trial. In the regional citrate group vs systemic heparin group, median filter life span was 47 hours (interquartile range [IQR], 19-70 hours) vs 26 hours (IQR, 12-51 hours) (difference, 15 hours [95% CI, 11 to 20 hours]; P < .001). Ninety-day all-cause mortality occurred in 150 of 300 patients vs 156 of 296 patients (Kaplan-Meier estimator percentages, 51.2% vs 53.6%; unadjusted difference, -2.4% [95% CI, -10.5% to 5.8%]; unadjusted hazard ratio, 0.91 [95% CI, 0.72 to 1.13]; unadjusted P = .38; adjusted difference, -6.1% [95% CI, -12.6% to 0.4%]; primary adjusted hazard ratio, 0.79 [95% CI, 0.63 to 1.004]; primary adjusted P = .054). Of 38 prespecified secondary end points, 34 showed no significant difference. Compared with the systemic heparin group, the regional citrate group had significantly fewer bleeding complications (15/300 [5.1%] vs 49/296 [16.9%]; difference, -11.8% [95% CI, -16.8% to -6.8%]; P < .001) and significantly more new infections (204/300 [68.0%] vs 164/296 [55.4%]; difference, 12.6% [95% CI, 4.9% to 20.3%]; P = .002). Conclusions and Relevance: Among critically ill patients with acute kidney injury receiving continuous kidney replacement therapy, anticoagulation with regional citrate, compared with systemic heparin anticoagulation, resulted in significantly longer filter life span. The trial was terminated early and was therefore underpowered to reach conclusions about the effect of anticoagulation strategy on mortality. Trial Registration: ClinicalTrials.gov Identifier: NCT02669589.
Authors 30
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Alexander Zarbock corresponding
Affiliation as printed
Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
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Affiliation as printed
Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
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Heinrich Heine University Düsseldorf
Affiliation as printed
Department of Anesthesiology and Critical Care Medicine, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany
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Affiliation as printed
Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
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Affiliation as printed
Institute of Biostatistics and Clinical Research, University of Münster, Münster, Germany
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Heinrich Heine University Düsseldorf
Affiliation as printed
Department of Anesthesiology and Critical Care Medicine, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany
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Heinrich Heine University Düsseldorf
Affiliation as printed
Department of Anesthesiology and Critical Care Medicine, Heinrich-Heine University of Düsseldorf, Düsseldorf, Germany
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Affiliation as printed
Department of Nephrology, University Hospital Essen, Essen, Germany
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Affiliation as printed
Department of Nephrology, University Hospital Essen, Essen, Germany
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Affiliation as printed
Department of Nephrology, University Hospital Essen, Essen, Germany
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Affiliation as printed
Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
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Affiliation as printed
Department of Anesthesiology and Intensive Care Medicine, University Hospital Tübingen, Eberhard Karls University Tübingen, Tübingen, Germany
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Affiliation as printed
Department of Intensive Care Medicine, University of Aachen, Aachen, Germany
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Affiliation as printed
Department of Intensive Care Medicine, University of Aachen, Aachen, Germany
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Affiliation as printed
Department of Anesthesiology and Intensive Care Medicine, University Hospital Augsburg, Augsburg, Germany
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Affiliation as printed
Department of Anesthesiology and Intensive Care Medicine, University Hospital Augsburg, Augsburg, Germany
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Affiliation as printed
University Hospital Bonn, Department of Anesthesiology and Intensive Care Medicine, Bonn, Germany
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Affiliation as printed
University Hospital Bonn, Department of Anesthesiology and Intensive Care Medicine, Bonn, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
University Medical Center Hamburg-Eppendorf, Department of Intensive Care, Hamburg, Germany
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University Medical Center Hamburg-Eppendorf
Affiliation as printed
University Medical Center Hamburg-Eppendorf, Department of Intensive Care, Hamburg, Germany
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Charité - Universitätsmedizin Berlin
Affiliation as printed
Department of Nephrology and Medical Intensive Care, Charité–Universitätsmedizin Berlin, Berlin, Germany
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University Medical Center of the Johannes Gutenberg University Mainz
Affiliation as printed
Universitätsmedizin Mainz, Department of Anesthesiology, Mainz, Germany
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Universitätsklinikum Würzburg · University Hospital Frankfurt
Affiliation as printed
Department of Anesthesiology, Intensive Care and Pain Medicine, University Hospital Frankfurt, Frankfurt, Germany
Department of Anesthesiology, University Hospital Würzburg, Würzburg, Germany
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Affiliation as printed
Department of Anesthesiology, Intensive Care and Pain Medicine, Helios Klinikum Bad Saarow, Bad Saarow, Germany
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Affiliation as printed
Department of Anesthesiology, University Medical Center Göttingen, Göttingen, Germany
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Affiliation as printed
Department of Anesthesiology and Intensive Care Medicine, University Hospital Jena, Jena, Germany
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Affiliation as printed
Department of Anesthesiology and Intensive Care Medicine, University Hospital Leipzig, Leipzig, Germany
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University of Alberta · Alberta Health Services
Affiliation as printed
Department of Critical Care Medicine, Faculty of Medicine and Dentistry, University of Alberta and Alberta Health Services, Edmonton, Alberta, Canada
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Affiliation as printed
Center for Critical Care Nephrology, Department of Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
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Affiliation as printed
Department of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany
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