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      Prostacyclin versus Citrate in Continuous Haemodiafiltration: An Observational Study in Patients with High Risk of Bleeding

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          Abstract

          Background: The efficacy and safety of prostacyclin (PGI<sub>2</sub>) and citrate (ACD) anticoagulation were observed and compared during continuous haemodiafiltration. Methods: Mechanically ventilated patients received either the PGI<sub>2</sub> analogue epoprostenol (group A, n = 17) in escalating doses of 4.5–10.0 ng·kg<sup>–1</sup>·min<sup>–1</sup> in combination with heparin (6 IU·kg<sup>–1</sup>·h<sup>–1</sup>) or 2.2% ACD (group B, n = 15). Blood flow was set to match the circuit-filling volume per unit time equal to the intravascular half-life of PGI<sub>2</sub>. Results: Median filter lifetimes were 26 h (interquartile range 16–37) in group A (39 filters) and 36.5 h (interquartile range 23–50) in group B (56 filters; p < 0.01). In group A, 4 patients (23.5%, p < 0.05) had the dose reduced due to hypotension. The final mean dose of PGI<sub>2</sub> was 8.7 ± 2.4 ng·kg<sup>–1</sup>·min<sup>–1</sup>. Four patients in group A (23.5%, p < 0.05) were switched to ACD due to a decrease in platelet count. No bleeding episodes, decrease in platelet count or adverse haemodynamic effects were encountered in group B. The cost of epoprostenol plus low dose heparin (EUR 204.73 ± 53.04) was significantly higher than the cost of ACD-based anticoagulation (EUR 93.92 ± 45.2, p < 0.05). Conclusion: ACD offers longer filter survival, has no impact on platelet count and is less expensive. Increasing the dose of PGI<sub>2</sub> up to the average of 8.7 ng·kg<sup>–1</sup>·min<sup>–1</sup> did not increase the haemodynamic side effects.

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          Citrate pharmacokinetics and metabolism in cirrhotic and noncirrhotic critically ill patients.

          To investigate pharmacokinetics and metabolism of sodium citrate in critically ill patients. To determine the risk of citrate accumulation in the setting of liver dysfunction (cirrhosis, hepatorenal syndrome). Prospective cohort study. Intensive Care Unit, Department of Medicine IV, University Hospital Vienna. Consecutive critically ill cirrhotic (n = 16) and noncirrhotic patients (n = 16). Infusion of sodium citrate (0.5 mmol.kg-1.hr-1) and calcium chloride (0.17 mmol.kg-1.hr-1) for 2 hrs. Analysis of serial arterial blood samples. Total body clearance of citrate was normal in noncirrhotic critically ill patients but significantly reduced in cirrhotic patients (710 vs. 340 mL/min, p =.008). Citrate peak concentrations and concentration over time were increased by 65% and 114% in cirrhotic patients (p <.001), respectively; volumes of distribution were similar. Net metabolic changes were quantitatively similar, with pH and plasma bicarbonate concentrations increasing more slowly in cirrhotic patients. No citrate-related side effects were noted. Citrate clearance could not be predicted by standard liver function tests and was not appreciably influenced by renal function and Acute Physiology and Chronic Health Evaluation II scores. This first systematic study on citrate pharmacokinetics and metabolism in critically ill patients confirms a major role of hepatic citrate metabolism by demonstrating reduced citrate clearance in cirrhotic patients. Pharmacokinetic data could provide a basis for the clinical use of citrate anticoagulation in critically ill patients. Provided dose adaptation and monitoring of ionized calcium, citrate anticoagulation seems feasible even in patients with decompensated cirrhosis. Metabolic consequences of citrate infusion were not different between groups in this study but may be more pronounced in prolonged infusion.
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            Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation.

            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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              Continuous veno-venous hemofiltration without anticoagulation in high-risk patients.

              To study the safety and operative efficacy of continuous veno-venous hemofiltration (CVVH) without anticoagulation in patients at high risk of bleeding. Prospective cohort study and comparison to control group. Tertiary, multidisciplinary intensive care unit. Forty hemofiltration circuits in 12 patients with severe acute renal failure (ARF) deemed at high risk of bleeding. Forty control circuits in 14 patients treated with low-dose pre-filter heparin infusion. CVVH at 21/h of pump-controlled ultrafiltration without anticoagulation or saline flush in patients at high risk of bleeding. Collection of data at the bedside. Mean circuit life was 32 h (95% CI: 20-44.4) in patients receiving CVVH without anticoagulation. Forty-three per cent of filters lasted longer than 30 h. Circuit lifespan did not correlate with international normalized ratio (INR), activated partial thromboplastin time (APTT) or platelet count. There were no bleeding complications and azotemic control was not compromised by lack of circuit anticoagulation with a mean serum urea of 16.0 mmol/l (95% CI: 14.9-18.1) during treatment. A control group of consecutive similarly ill patients not at high risk of bleeding received low-dose pre-filter heparin (mean dose 716 IU; 95% CI: 647-785). Their mean filter life was 19.5 h (95% CI: 14.2-23.8), significantly shorter than in the study patients (p = 0.017). Critically ill patients at high risk of bleeding who require continuous renal replacement therapy (CRRT) can be safely managed without circuit anticoagulation. This strategy minimizes bleeding risks and is associated with an acceptable filter life. CRRT without anticoagulation should be strongly considered in high-risk patients.
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                Author and article information

                Journal
                BPU
                Blood Purif
                10.1159/issn.0253-5068
                Blood Purification
                S. Karger AG
                0253-5068
                1421-9735
                2005
                September 2005
                04 October 2005
                : 23
                : 4
                : 325-329
                Affiliations
                Department Anaesthesia and Intensive Care, University Hospital Kralovske Vinohrady, Prague, Czech Republic
                Article
                87770 Blood Purif 2005;23:325–329
                10.1159/000087770
                16118487
                aa4ae4eb-4341-4a04-98fd-224e1226a099
                © 2005 S. Karger AG, Basel

                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
                : 27 May 2005
                Page count
                Figures: 1, Tables: 1, References: 21, Pages: 5
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Acute renal failure,Renal replacement therapy,Haemodiafiltration,Citrate,Prostacyclin

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