Benefits and harms of citrate locking solutions for hemodialysis catheters: a systematic review and meta-analysis

Alexa Grudzinski, Arnav Agarwal, Neera Bhatnagar, Gihad Nesrallah, Alexa Grudzinski, Arnav Agarwal, Neera Bhatnagar, Gihad Nesrallah

Abstract

Background: Citrate has theoretical advantages over heparin for locking hemodialysis central venous catheters (CVCs), but the comparative effectiveness of these agents is not clear.

Objectives: 1) To compare the benefits and harms of citrate versus heparin locking solutions among patients undergoing hemodialysis through CVCs; 2) to appraise methodological quality of the supporting evidence.

Data sources: CENTRAL, MEDLINE, EMBASE, CINAHL, ISI Web of Science, and nephrology conference abstracts.

Study eligibility participants and interventions: We included randomized, parallel arm clinical trials that enrolled adult patients (>18 years) receiving chronic hemodialysis through CVCs using a citrate locking solution. We excluded studies in which citrate was combined with other agents, such as antibiotics.

Appraisal and synthesis methods: We used the GRADE approach to systematic reviews and quality appraisal. Two reviewers performed data extraction independently and in duplicate. We pooled count data using generic inverse variance with random-effects models, and used fixed-effect models when only two studies were available for pooling. Subgroups included low (≤5%) vs. higher (≥30%) citrate.

Results: We screened 600 citations. Forty-one proceeded to full-text screen; 5 met inclusion criteria. Studies included between 19 and 291 participants (Median N = 61) followed for a total of 174.6 catheter-years; 2 were multi-centred trials. Three studies assessed all-cause mortality; the pooled relative risk for death was 0.71 (95% CI = 0.42-1.24; p = 0.21; I(2) = 0%). The rate ratio for bacteremic episodes was 0.54 (95% CI = 0.23-1.29; p = 0.16; I(2) = 65%) while the rate ratio for bleeding was 0.48 (95% CI = 0.3-0.75; p = 0.001;I I(2) = 5%). Rates of catheter exchange/replacement, all-cause hospitalization and in-situ thrombolysis were not significantly different between groups in any of the pooled analyses. Risk of bias within pooled studies was low.

Limitations: Outcome definitions varied across studies. Imprecision due to small sample sizes and low event rates reduce our overall confidence in the pooled effect estimates.

Implications: Benefits and harms of citrate vs. heparin locking solutions remain unclear; larger studies and standardization of outcome measurement and reporting are warranted.

Trial registration: Protocol Registration Number: CRD42013004781.

Figures

Figure 1
Figure 1
Study inclusion flow diagram.
Figure 2
Figure 2
Comparative risk of death (all-cause) with citrate vs. heparin locking solutions.
Figure 3
Figure 3
Comparative risk of bacteremia with citrate vs. heparin locking solutions.
Figure 4
Figure 4
Comparative risk of bleeding with citrate vs. heparin locking solutions.
Figure 5
Figure 5
Comparative risk of CVC replacement for impaired patency with citrate vs. heparin locking solutions.
Figure 6
Figure 6
Comparative risk of hospitalization (any cause) with citrate vs. heparin locking solutions.

References

    1. Ethier J, Mendelssohn DC, Elder SJ, Hasegawa T, Akizawa T, Akiba T, et al. Vascular access use and outcomes: an international perspective from the dialysis outcomes and practice patterns study. Nephrol Dial Transplant. 2008;23:3219–26. doi: 10.1093/ndt/gfn261.
    1. Ivan DM, Smith T, Allon M. Does the heparin lock concentration affect hemodialysis catheter patency? Clin J Am Soc Nephrol. 2010;5:1458–62. doi: 10.2215/CJN.01230210.
    1. Rioux JP, De Bortoli B, Querin S, Deziel C, Troyanov S, Madore F. Measurement of the international normalized ratio (INR) in hemodialysis patients with heparin-locked central venous catheters: evaluation of a novel blood sampling method. J Vasc Access. 2009;10:180–2.
    1. Syed S, Reilly RF. Heparin-induced thrombocytopenia: a renal perspective. Nat Rev Nephrol. 2009;5:501–11. doi: 10.1038/nrneph.2009.125.
    1. Berkun Y, Haviv YS, Schwartz LB, Shalit M. Heparin-induced recurrent anaphylaxis. Clin Exp Allergy. 2004;34:1916–8. doi: 10.1111/j.1365-2222.2004.02129.x.
    1. Citrate locking solutions for hemodialysis catheters: a systematic review and meta-analysis [Available from: ]
    1. Guyatt GH, Oxman AD, Kunz R, Atkins D, Brozek J, Vist G, et al. GRADE guidelines: 2. Framing the question and deciding on important outcomes. J Clin Epidemiol. 2011;64:395–400. doi: 10.1016/j.jclinepi.2010.09.012.
    1. Guyatt G, Oxman AD, Sultan S, Brozek J, Glasziou P, Alonso-Coello P, et al. GRADE guidelines 11-making an overall rating of confidence in effect estimates for a single outcome and for all outcomes. J Clin Epidemiol. 2013;66:151–7. doi: 10.1016/j.jclinepi.2012.01.006.
    1. Guyatt G, Oxman AD, Akl EA, Kunz R, Vist G, Brozek J, et al. GRADE guidelines: 1. Introduction-GRADE evidence profiles and summary of findings tables. J Clin Epidemiol. 2011;64:383–94. doi: 10.1016/j.jclinepi.2010.04.026.
    1. Balshem H, Helfand M, Schunemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011;64:401–6. doi: 10.1016/j.jclinepi.2010.07.015.
    1. Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, et al. The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ. 2009;339:b2700. doi: 10.1136/bmj.b2700.
    1. The Cochrane Library []
    1. DistillerSR []
    1. Guyatt GH, Oxman AD, Vist G, Kunz R, Brozek J, Alonso-Coello P, et al. GRADE guidelines: 4. Rating the quality of evidence–study limitations (risk of bias) J Clin Epidemiol. 2011;64:407–15. doi: 10.1016/j.jclinepi.2010.07.017.
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 8. Rating the quality of evidence–indirectness. J Clin Epidemiol. 2011;64:1303–10. doi: 10.1016/j.jclinepi.2011.04.014.
    1. Guyatt GH, Oxman AD, Kunz R, Brozek J, Alonso-Coello P, Rind D, et al. GRADE guidelines 6. Rating the quality of evidence–imprecision. J Clin Epidemiol. 2011;64:1283–93. doi: 10.1016/j.jclinepi.2011.01.012.
    1. Guyatt GH, Oxman AD, Kunz R, Woodcock J, Brozek J, Helfand M, et al. GRADE guidelines: 7. Rating the quality of evidence–inconsistency. J Clin Epidemiol. 2011;64:1294–302. doi: 10.1016/j.jclinepi.2011.03.017.
    1. Guyatt GH, Oxman AD, Montori V, Vist G, Kunz R, Brozek J, et al. GRADE guidelines: 5. Rating the quality of evidence–publication bias. J Clin Epidemiol. 2011;64:1277–82. doi: 10.1016/j.jclinepi.2011.01.011.
    1. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928. doi: 10.1136/bmj.d5928.
    1. Higgins JP, Thompson SG, Spiegelhalter DJ. A re-evaluation of random-effects meta-analysis. J R Stat Soc Ser A Stat Soc. 2009;172:137–59. doi: 10.1111/j.1467-985X.2008.00552.x.
    1. Buturovic J, Ponikvar R, Kandus A, Boh M, Klinkmann J, Ivanovich P. Filling hemodialysis catheters in the interdialytic period: heparin versus citrate versus polygeline: a prospective randomized study. Artif Organs. 1998;22:945–7. doi: 10.1046/j.1525-1594.1998.06268.x.
    1. Hendrickx L, Kuypers D, Evenepoel P, Maes B, Messiaen T, Vanrenterghem Y. A comparative prospective study on the use of low concentrate citrate lock versus heparin lock in permanent dialysis catheters. Int J Artif Organs. 2001;24:208–11.
    1. Macrae JM, Dojcinovic I, Djurdjev O, Jung B, Shalansky S, Levin A, et al. Citrate 4% versus heparin and the reduction of thrombosis study (CHARTS) Clin J Am Soc Nephrol. 2008;3:369–74. doi: 10.2215/CJN.01760407.
    1. Power A, Duncan N, Singh SK, Brown W, Dalby E, Edwards C, et al. Sodium citrate versus heparin catheter locks for cuffed central venous catheters: a single-center randomized controlled trial. Am J Kidney Dis. 2009;53:1034–41. doi: 10.1053/j.ajkd.2009.01.259.
    1. Weijmer MC, van den Dorpel MA, Van de Ven PJG, ter Wee PM, van Geelen JACA, Groeneveld JO, et al. Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients. J Am Soc Nephrol. 2005;16:2769–77. doi: 10.1681/ASN.2004100870.
    1. Zhao Y, Li Z, Zhang L, Yang J, Yang Y, Tang Y, et al. Citrate versus heparin lock for hemodialysis catheters: a systematic review and meta-analysis of randomized controlled trials. Am J Kidney Dis. 2014;63:479–90. doi: 10.1053/j.ajkd.2013.08.016.
    1. Labriola L, Crott R, Jadoul M. Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials. Nephrol Dial Transplant. 2008;23:1666–72. doi: 10.1093/ndt/gfm847.
    1. Yahav D, Rozen-Zvi B, Gafter-Gvili A, Leibovici L, Gafter U, Paul M. Antimicrobial lock solutions for the prevention of infections associated with intravascular catheters in patients undergoing hemodialysis: systematic review and meta-analysis of randomized, controlled trials. Clin Infect Dis. 2008;47:83–93. doi: 10.1086/588667.
    1. Ash SR, Mankus RA, Sutton JM, Smeltzer B, Ing T. CONCENTRATED CITRATE (23%) FOR CATHETER LOCK SOLUTION. ASAIO J. 2000;46:222. doi: 10.1097/00002480-200003000-00286.
    1. Winnett G, Nolan J, Miller M, Ashman N. Trisodium citrate 46.7% selectively and safely reduces staphylococcal catheter-related bacteraemia. Nephrol Dial Transplant. 2008;23:3592–8. doi: 10.1093/ndt/gfn299.
    1. Shanks RM, Sargent JL, Martinez RM, Graber ML, O’Toole GA. Catheter lock solutions influence staphylococcal biofilm formation on abiotic surfaces. Nephrol Dial Transplant. 2006;21:2247–55. doi: 10.1093/ndt/gfl170.
    1. Regamey C, Schaberg D, Kirby WM. Inhibitory effect of heparin on gentamicin concentrations in blood. Antimicrob Agents Chemother. 1972;1:329–32. doi: 10.1128/AAC.1.4.329.
    1. Weijmer MC, Debets-Ossenkopp YJ, Van De Vondervoort FJ, ter Wee PM. Superior antimicrobial activity of trisodium citrate over heparin for catheter locking. Nephrol Dial Transplant. 2002;17:2189–95. doi: 10.1093/ndt/17.12.2189.
    1. Grudzinski L, Quinan P, Kwok S, Pierratos A. Sodium citrate 4% locking solution for central venous dialysis catheters–an effective, more cost-efficient alternative to heparin. Nephrol Dial Transplant. 2007;22:471–6. doi: 10.1093/ndt/gfl606.
    1. Moran JE, Ash SR, Committee ACP. Locking solutions for hemodialysis catheters; heparin and citrate–a position paper by ASDIN. Semin Dial. 2008;21:490–2. doi: 10.1111/j.1525-139X.2008.00466.x.
    1. Vanholder R, Canaud B, Fluck R, Jadoul M, Labriola L, Marti-Monros A, et al. Catheter-related blood stream infections (CRBSI): a European view. Nephrol Dial Transplant. 2010;25:1753–6. doi: 10.1093/ndt/gfq205.
    1. Manns BJ, Scott-Douglas N, Tonelli M, Ravani P, LeBlanc M, Dorval M, et al. An Economic Evaluation of rt-PA Locking Solution in Dialysis Catheters. J Am Soc Nephrol. 2014;25:2887–95. doi: 10.1681/ASN.2013050463.
    1. Hemmelgarn BR, Moist LM, Lok CE, Tonelli M, Manns BJ, Holden RM, et al. Prevention of dialysis catheter malfunction with recombinant tissue plasminogen activator. N Engl J Med. 2011;364:303–12. doi: 10.1056/NEJMoa1011376.
    1. Mustafa RA, Zimmerman D, Rioux JP, Suri RS, Gangji A, Steele A, et al. Vascular access for intensive maintenance hemodialysis: a systematic review for a canadian society of nephrology clinical practice guideline. Am J Kidney Dis. 2013;62:112–31. doi: 10.1053/j.ajkd.2013.03.028.
    1. Lee T, Mokrzycki M, Moist L, Maya I, Vazquez M, Lok CE. Standardized definitions for hemodialysis vascular access. Semin Dial. 2011;24:515–24. doi: 10.1111/j.1525-139X.2011.00969.x.

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere