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      Metabolic Complications during Regional Citrate Anticoagulation in Continuous Venovenous Hemodialysis: Single-Center Experience

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          Abstract

          Background: Regional anticoagulation with trisodium citrate is an effective form of anticoagulation for continuous renal replacement therapy (CRRT) in patients at a high risk of bleeding. In a prospective, observational study we compared an established regional citrate anticoagulation protocol [Mehta R et al: Kidney Int 1990;38:976–981] versus a standard heparin anticoagulation protocol focusing on acid-base and electrolyte derangements as well as on cost effectiveness. Methods and Results: 209 patients were included in the study. In 37 patients, citrate was used as the sole anticoagulant, 87 patients received low-dose heparin plus citrate, and 85 patients received only heparin as anticoagulant. A customized dialysate solution was used for citrate-anticoagulated CRRT (no buffer, no calcium, reduced sodium concentration). Filter life was significantly higher during citrate anticoagulation compared to heparin anticoagulation (80.2 ± 60 vs. 30.2 ± 32 h; p < 0.001). No difference was found between citrate and citrate-heparin anticoagulation (p = 0.310). Metabolic alkalosis was observed in more than 50% of patients on citrate anticoagulation. Alkalosis developed within the first 72 h after initiating treatment and could be reversed in almost all cases by increasing the dialysate flow rate. Hypercalcemia was observed in 13 patients on citrate anticoagulation. Patients with impaired liver function were particularly at risk. Systemic hypocalcemia, hypernatremia, and anion gap acidosis were not observed. Citrate anticoagulation was well tolerated hemodynamically. A longer filter life during citrate anticoagulation translated into a significant cost reduction compared to standard heparin anticoagulation (p < 0.01). Conclusion: Regional anticoagulation with trisodium citrate in combination with a customized calcium-free dialysate is a safe and effective alternative to a heparin-based anticoagulation regimen.

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          Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients.

          Ravindra Mehta, Brian Mcdonald, May Aguilar … (1990)
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            Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation.

            H Meier-Kriesche, J Gitomer, K Finkel … (2001)
            Citrate anticoagulation is commonly used for continuous venovenous hemodialysis (CVVHD) to minimize the risk of bleeding complications. We have previously reported a liver failure patient undergoing citrate-based CVVHD with elevated serum total to ionized calcium ratio. Diminished liver metabolism of citrate with resultant elevated systemic citrate was thought to be the cause. To determine the incidence and clinical significance of an elevated total to ionized calcium ratio during citrate-based CVVHD, 161 patients undergoing citrate-based CVVHD were screened for the presence of an elevated total to ionized calcium ratio (the subset with increased total to ionized calcium ratio comprised the study group). Because all patients in the study group had liver failure, two control groups of patients with normal total to ionized calcium ratios were formed-those without liver failure (control I) and those with liver failure (control II). An elevated total to ionized calcium ratio was detected in 12% of all patients. Thirty-three percent of liver failure patients demonstrated an elevated total to ionized calcium ratio. The study group demonstrated significantly higher mean total calcium levels, significantly lower mean ionized calcium levels, and significantly higher mean total to ionized calcium ratios than controls. As a result, the study group also had significantly increased mean calcium chloride replacement requirements in comparison with controls. The mean calcium to citrate infusion ratio was elevated in the study group in comparison with controls. An elevated total to ionized calcium ratio was associated with increased mortality in comparison with controls. No patients suffered complications from ionized hypocalcemia or elevated serum total calcium. Systemic citrate accumulation as evidenced by an elevated total to ionized calcium ratio occurs commonly in patients requiring CVVHD using citrate-based regional anticoagulation. Observing changes in the total to ionized calcium ratio can aid in early detection of patients with hepatic failure who are unable to appropriately metabolize citrate and will require calcium chloride infusion rates significantly above normal.
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              Hypocalcemia in critically ill patients.

              Gary Zaloga (1992)
              To review calcium regulation, causes of hypocalcemia during critical illness, clinical features and treatment of hypocalcemia, hemodynamic effects of calcium administration, calcium-catecholamine interactions, and the role of calcium in ischemic injury. Representative articles from the medical literature are used to support the discussion of selected aspects of calcium metabolism which are important to the practice of critical care medicine. Results from both animal and human investigations and both in vitro and in vivo studies are discussed. Circulating calcium levels are best measured using ionized calcium electrodes. Ionized hypocalcemia is common in critically ill patients and usually results from impaired parathyroid hormone secretion or action, impaired vitamin D synthesis or action, or calcium chelation/precipitation. Ionized hypocalcemia most commonly presents as cardiovascular or neuromuscular insufficiency. Mild ionized hypocalcemia (greater than 0.8 mmol/L) is usually asymptomatic and frequently does not require treatment. Moderate-to-severe ionized hypocalcemia is best treated with iv calcium in the critically ill patient. The majority of studies report no increase in cardiac output but a significant increase in BP after iv calcium administration. When administered with beta-adrenergic agonists, calcium frequently impairs their cardiovascular actions. Intracellular calcium dysregulation is common during ischemic and shock states. Agents which increase intracellular calcium may be harmful during cellular ischemia. Alterations in calcium regulation and calcium concentrations are common during critical illness. Optimal management of altered calcium concentrations requires an understanding of the pathophysiology behind these alterations.
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                Author and article information

                Journal
                Journal ID (publisher-id): NEC
                Journal ID (nlm-ta): Nephron Clin Pract
                Journal ID (doi): 10.1159/issn.1660-2110
                Title: Nephron Clinical Practice
                Publisher: S. Karger AG
                ISSN (Electronic): 1660-2110
                Publication date Subscription-year: 2004
                Publication date (Print): August 2004
                Publication date (Electronic): 17 November 2004
                Volume: 97
                Issue: 4
                Pages: c131-c136
                Affiliations
                Departments of aNephrology, bAnesthesiology, cCardiology, dInfectious Diseases and eSurgery, Charité, Humboldt University of Berlin, Germany
                Article
                Publisher ID: 79171 Other ID: Nephron Clin Pract 2004;97:c131–c136
                DOI: 10.1159/000079171
                PubMed ID: 15331942
                SO-VID: b01eb797-b2cc-4a14-8897-64c5b6939c80
                Copyright © © 2004 S. Karger AG, Basel
                License:

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Date received : 19 September 2003
                Date accepted : 24 February 2004
                Page count
                Figures: 3, Tables: 1, References: 21, Pages: 1
                Categories
                Subject: Original Paper

                ScienceOpen disciplines: Cardiovascular Medicine,Nephrology
                Keywords: Metabolic complications,Continuous renal replacement therapy,Citrate anticoagulation
                Data availability:
                ScienceOpen disciplines: Cardiovascular Medicine, Nephrology
                Keywords: Metabolic complications, Continuous renal replacement therapy, Citrate anticoagulation

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