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      Filter Run Time in CVVH: Pre- versus Post-Dilution and Nadroparin versus Regional Heparin-Protamine Anticoagulation

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          Background/Aims: To study the effect of different modes of continuous veno-venous haemofiltration (CVVH) on filter run time (FRT). Methods: We studied, in two consecutive prospective, randomised and crossover studies, 16 and 15 patients with acute renal failure during critical illness. Study A compared pre- versus post-dilution, and study B compared regional anticoagulation with heparin (pre-filter) and protamine (post-filter) (HP) versus nadroparin (NP) pre-filter. All CVVH sessions were standardised. Analyses were by Wilcoxon rank sum tests. Results: Study A: During pre-dilution the median FRT was 45.7 vs. 16.1 h in post-dilution CVVH (p = 0.005). The median creatinine clearance during pre-dilution was 33 vs. 45 ml/min in post-dilution (p = 0.001). Study B: During NP, median FRT was 39.5 vs. 12.3 h during HP CVVH (p = 0.045). Conclusions: Pre-dilution CVVH results in the greatest FRT but a lower plasma creatinine clearance compared to post-dilution. Regional anticoagulation with heparin-protamine resulted in a significantly shorter FRT compared to systemic NP anticoagulation.

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          A controlled trial of low-molecular-weight heparin (dalteparin) versus unfractionated heparin as anticoagulant during continuous venovenous hemodialysis with filtration.

          To compare the efficacy, safety, and cost of fixed-dose low-molecular-weight heparin (dalteparin) with adjusted-dose unfractionated heparin as anticoagulant for continuous hemofiltration. Prospective, randomized, controlled clinical trial. University-affiliated adult intensive care unit All patients requiring continuous hemofiltration for acute renal failure or systemic inflammatory response syndrome (SIRS) were eligible. Fifty-seven patients were enrolled. Eleven were excluded, seven because of major protocol violations and four died before hemofiltration. Patients received continuous venovenous hemodialysis with filtration with prefilter replacement at 500 mL/hr and countercurrent dialysate at 1000 mL/hr. Filters were primed with normal saline containing anticoagulant. Dalteparin-treated patients received a commencement bolus of 20 units/kg and a maintenance infusion at 10 units/kg/hr. Heparin-treated patients received a commencement bolus of 2000-5000 units and a maintenance infusion at 10 units/kg/hr, titrated to achieve an activated partial thromboplastin time in the patient of 70-80 secs. The primary outcome measure--time to failure of the hemofilter--was compared using survival analysis. Twenty-two patients (13 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to heparin. Twenty-five patients (16 with acute renal failure and nine with SIRS; total, 41 filters) were randomized to dalteparin. Mean (SE) activated partial thromboplastin time in the heparin group was 79 (4.3) secs. Mean (SE) anti-factor-Xa activity in the six patients given dalteparin who were assayed was 0.49 (0.07). Mean (SE) prehemofiltration platelet count was 225 (35.5) x 10(9) for heparin and 178 (18.1) x 10(9) for dalteparin (p = .24, unpaired Student's t-test). Mean (SE) prehemofiltration hemoglobin was 11.4 (0.61) g/dL for heparin and 10.6 (0.38) g/dL for dalteparin (p = .31, unpaired Student's t-test). There was no significant difference in the time to failure between the two groups (p = .75, log rank test). For dalteparin, Kaplan-Meier (K-M) mean (SE) time to failure of the hemofilter was 46.8 (5.03) hrs. For heparin, K-M mean (SE) time to failure was 51.7 (7.51) hrs. The 95% CI for difference in mean time to failure was -13 to 23 hrs. The power of this study to detect a 50% change in filter life was >90%. Mean (SE) reduction in platelet count during hemofiltration was 63 (25.8) x 10(9) for heparin and 41.8 (26.6) x 10(9) for dalteparin (p = .57, unpaired Student's t-test). Eight patients given dalteparin and four patients given heparin had screening for heparin-induced thrombocytopenia; three of the dalteparin patients and one of the heparin patients were positive (p = 1.0, Fisher's exact test). There were three episodes of trivial bleeding and two episodes of significant bleeding for dalteparin, and there were three episodes of trivial bleeding and four episodes of significant bleeding for heparin (p = .53, chi-square test). The mean (SE) decrease in hemoglobin concentration during hemofiltration was 0.51 (0.54) g/dL for heparin and 0.28 (0.49) g/dL for dalteparin (p = .75, unpaired Student's t-test). The mean (SE) packed-cell transfusion volume during hemofiltration was 309 (128) mL for heparin and 290 (87) mL for dalteparin (p = .90, unpaired Student's t-test). Daily costs, including coagulation assays, of hemofiltration were approximately 10% higher using dalteparin than with heparin. Fixed-dose dalteparin provided identical filter life, comparable safety, but increased total daily cost compared with adjusted-dose heparin. Unfractionated heparin remains our anticoagulant of choice for continuous hemofiltration in intensive care.
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            Anticoagulation in continuous renal replacement therapy.

            Continuous renal replacement therapies (CRRTs) allow for gradual solute and fluid removal. In very sick patients with acute renal failure, they may be better tolerated than hemodialysis. The major drawback to CRRTs is the need for anticoagulation to maintain filter patency. The patients who are likely to benefit from CRRTs are also at higher risk for bleeding from systemic anticoagulation. The most commonly used form of anticoagulation for CRRTs, low-dose heparin, causes bleeding in 10-50% of patients. Regional anticoagulation using protamine may reduce the risk of bleeding, but it is difficult to use. Low molecular weight heparin and prostacyclin both may partially reduce bleeding, but are difficult to dose. Regional anticoagulation with citrate is easy to use and has been shown to prolong filter life without systemic anticoagulation. It is the anticoagulant of choice for most patients on CRRT.
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              Hirudin versus heparin for anticoagulation in continuous renal replacement therapy.

              To compare the efficacy and safety of hirudin and heparin for anticoagulation during continuous renal replacement therapy (CRRT) in critically ill patients. Prospective, randomized controlled pilot study. Single centre; interdisciplinary intensive care unit at a university hospital. Seventeen patients receiving CRRT. Patients were randomly allocated to two groups. Heparin group (nine patients): continuous administration of 250 IU/h heparin; dose was adjusted in 125 IU/h steps with a targeted activated clotting time (ACT) of 180-210 s. Hirudin group (eight patients): continuous infusion of 10 micrograms/kg/h hirudin, dose was adjusted in 2 micrograms/kg/h steps with a targeted ecarin clotting time (ECT) of 80-100 s. Observation time was 96 h. Measured filter run patency and haemofiltration efficacy did not significantly differ between the two groups. Three bleeding complications were observed in the hirudin group, none in the heparin group (P < 0.01). At the onset of bleeding, which occurred 60 or more hours after the start of therapy, only one patient was still under continuous hirudin administration but levels were either in therapeutic range or below. Hirudin can be used efficiently for anticoagulation in CRRT. Late bleeding complications may have been caused by possible hirudin accumulation, but this was not evident from hirudin plasma and ECT levels. Since bleeding complications were observed only in the presence of documented coagulation disorders, not only adequate drug monitoring but also the plasmatic and cellular coagulation status of the patient should be taken into consideration for adjusting hirudin dosage.

                Author and article information

                Blood Purif
                Blood Purification
                S. Karger AG
                May 2005
                19 May 2005
                : 23
                : 3
                : 175-180
                Department of Intensive Care, Medical Centre Leeuwarden, Leeuwarden, The Netherlands
                83938 Blood Purif 2005;23:175–180
                © 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.

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                Tables: 3, References: 14, Pages: 6
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