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      An Observational Study on the Effects of Nadroparin-Based and Citrate-Based Continuous Venovenous Hemofiltration on Calcium Metabolism

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          Backgrounds: To study calcium homeostasis during citrate-based compared to nadroparin-based CVVH in critically-ill patients with acute renal failure. Methods: 11 patients were observed during citrate anticoagulation, 9 with nadroparin and 10 controls. Citrate was chosen for patients with active or at risk for bleeding. Results: The controls had, at 24 h, a median serum iCa of 1.1 mmol/l, the citrate group 0.87 mmol/l and the nadroparin group 1.1 mmol/l (citrate vs. control p = 0.001, citrate vs. nadroparin p = 0.002). At 48 h, iCa was not significantly different anymore. Ca balance was negative for the citrate group in contrast to the nadroparin group (p = 0.012). Median serum PTH was higher (30.0 pmol/l vs. 6.5 pmol/l, p = 0.003) in the citrate group. Conclusion: With a relative low target-serum-iCa (0.8–0.9 mmol/l) citrate CVVH-treated patients had a negative daily calcium balance and a temporarily lower iCa level resulting in an enhanced PTH response in comparison to nadroparin.

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

            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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              Bone turnover in prolonged critical illness: effect of vitamin D.

              In prolonged critical illness, increased bone resorption and osteoblast dysfunction have been reported facing low 25 hydroxy vitamin D [25(OH)D] concentrations. The current study investigates the extent to which lack of nutritional vitamin D and time in intensive care contribute to bone loss in the critically ill. Prolonged critically ill patients (n = 22) were compared with matched controls and then randomized to daily vitamin D supplement of either +/- 200 IU (low dose) or +/- 500 IU (high dose). At intensive care admission, serum concentrations of 25(OH)D, 1,25 dihydroxyvitamin D(3), vitamin D-binding protein, ionized calcium, IL-1, and soluble IL-6-receptor were low, and PTH was normal. Circulating type-I collagen propeptides were high, alkaline phosphatase was normal, and osteocalcin was low. Bone resorption markers [(carboxy terminal cross-linked telopeptide of type I collagen (betaCTX), pyridinoline, deoxypyridinoline (DPD)] were 6-fold increased. Serum C-reactive protein (CRP) was 40-fold, IL-6 400-fold, TNFalpha levels 5-fold, and osteoprotegerin concentrations 3-fold higher than in controls. Soluble receptor activator of nuclear factor kappaB ligand was undetectable. High-dose vitamin D only slightly increased circulating 25 hydroxy vitamin D (P < 0.05), but 1,25 dihydroxyvitamin D(3) was unaltered. High-dose vitamin D slightly increased serum osteocalcin (P < 0.05) and decreased carboxy terminal propeptide type-I collagen (P < 0.05) but did not affect other bone turnover markers. Bone-specific alkaline phosphatase, urinary pyridinoline and DPD, and serum betaCTX markedly increased with time (P < 0.01). Circulating CRP and IL-6 decreased with time, whereas TNFalpha and IL-1 remained unaltered. The fall in CRP and IL-6 was more pronounced with the high- than low-dose vitamin D (P < 0.05). Except for a mirroring of betaCTX rise by a fall in osteoprotegerin, cytokines were unrelated to the progressively aggravating bone resorption. In conclusion, prolonged critically ill patients were vitamin D deficient. The currently recommended vitamin D dose did not normalize vitamin D status. Furthermore, severe bone hyperresorption further aggravated (up to 15-fold the normal values) with time in intensive care and was associated with impaired osteoblast function.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                July 2007
                19 April 2007
                : 25
                : 3
                : 267-273
                Departments of aIntensive Care, bInternal Medicine and cClinical Chemistry, Medical Centre Leeuwarden, Leeuwarden, and dDepartment of Intensive Care, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
                101853 Blood Purif 2007;25:267–273
                © 2007 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.

                Page count
                Figures: 4, Tables: 2, References: 15, Pages: 7
                Original Paper

                Cardiovascular Medicine, Nephrology

                Calcium, Critically ill, Parathyroid hormone, Hemofiltration, Vitamin D


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