Trisodium citrate 4% versus heparin as a catheter lock for non-tunneled hemodialysis catheters in critically ill patients: a multicenter, randomized clinical trial

Jean-Pierre Quenot, Julie Helms, Abderrahmane Bourredjem, Auguste Dargent, Ferhat Meziani, Julio Badie, Gilles Blasco, Gaël Piton, Gilles Capellier, Chaouki Mezher, Jean-Michel Rebibou, Abdelouaid Nadji, Thomas Crepin, Saber Davide Barbar, Camille Fleck, Amélie Cransac, Mathieu Boulin, Christine Binquet, Agnès Soudry-Faure, Rémi Bruyère, VERROU-REA Trial Investigators and the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis), Jean-Pierre Quenot, Julie Helms, Abderrahmane Bourredjem, Auguste Dargent, Ferhat Meziani, Julio Badie, Gilles Blasco, Gaël Piton, Gilles Capellier, Chaouki Mezher, Jean-Michel Rebibou, Abdelouaid Nadji, Thomas Crepin, Saber Davide Barbar, Camille Fleck, Amélie Cransac, Mathieu Boulin, Christine Binquet, Agnès Soudry-Faure, Rémi Bruyère, VERROU-REA Trial Investigators and the CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis)

Abstract

Background: Non-tunneled hemodialysis catheters are currently used for critically ill patients with acute kidney injury requiring extracorporeal renal replacement therapy. Strategies to prevent catheter dysfunction and infection with catheter locks remain controversial.

Methods: In a multicenter, randomized, controlled, double-blind trial, we compared two strategies for catheter locking of non-tunneled hemodialysis catheters, namely trisodium citrate at 4% (intervention group) versus unfractionated heparin (control group), in patients aged 18 years or older admitted to the intensive care unit and in whom a first non-tunneled hemodialysis catheter was to be inserted by the jugular or femoral vein. The primary endpoint was length of event-free survival of the first non-tunneled hemodialysis catheter. Secondary endpoints were: rate of fibrinolysis, incidence of catheter dysfunction and incidence of catheter-related bloodstream infection (CRBSI), all per 1000 catheter-days; number of hemorrhagic events requiring transfusion, length of stay in intensive care and in hospital; 28-day mortality.

Results: Overall, 396 randomized patients completed the trial: 199 in the citrate group and 197 in the heparin group. There was no significant difference in baseline characteristics between groups. The duration of event-free survival of the first non-tunneled hemodialysis catheter was not significantly different between groups: 7 days (IQR 3-10) in the citrate group and 5 days (IQR 3-11) in the heparin group (p = 0.51). Rates of catheter thrombosis, CRBSI, and adverse events were not statistically different between groups.

Conclusions: In critically ill patients, there was no significant difference in the duration of event-free survival of the first non-tunneled hemodialysis catheter between trisodium citrate 4% and heparin as a locking solution. Catheter thrombosis, catheter-related infection, and adverse events were not statistically different between the two groups. Trial registration Registered with Clinicaltrials.gov under the number NCT01962116. Registered 14 October 2013.

Keywords: Acute renal failure; Catheters; Citra-Lock; Critical illness; Hemodialysis; Heparin.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart of the VERROU-REA study population (N = 396)
Fig. 2
Fig. 2
Event-free survival of the first non-tunneled hemodialysis catheter in the citrate and heparin groups

References

    1. McGee DC, Gould MK. Preventing complications of central venous catheterization. N Engl J Med. 2003;348:1123–1133. doi: 10.1056/NEJMra011883.
    1. Siempos II, Kopterides P, Tsangaris I, Dimopoulou I, Armaganidis AE. Impact of catheter-related bloodstream infections on the mortality of critically ill patients: a meta-analysis. Crit Care Med. 2009;37:2283–2289. doi: 10.1097/CCM.0b013e3181a02a67.
    1. Murray PT, Hursting MJ. Heparin-induced thrombocytopenia in patients administered heparin solely for hemodialysis. Ren Fail. 2006;28:537–539. doi: 10.1080/08860220600843813.
    1. Berkun Y, Haviv YS, Schwartz LB, Shalit M. Heparin-induced recurrent anaphylaxis. Clin Exp Allergy. 2004;34:1916–1918. doi: 10.1111/j.1365-2222.2004.02129.x.
    1. Lok CE, Mokrzycki MH. Prevention and management of catheter-related infection in hemodialysis patients. Kidney Int. 2011;79:587–598. doi: 10.1038/ki.2010.471.
    1. Landry DL, Braden GL, Gobeille SL, Haessler SD, Vaidya CK, Sweet SJ. Emergence of gentamicin-resistant bacteremia in hemodialysis patients receiving gentamicin lock catheter prophylaxis. Clin J Am Soc Nephrol. 2010;5:1799–1804. doi: 10.2215/CJN.01270210.
    1. Dixon JJ, Steele M, Makanjuola AD. Anti-microbial locks increase the prevalence of Staphylococcus aureus and antibiotic-resistant Enterobacter: observational retrospective cohort study. Nephrol Dial Transplant. 2012;27:3575–3581. doi: 10.1093/ndt/gfs081.
    1. Souweine B, Lautrette A, Gruson D, Canet E, Klouche K, Argaud L, et al. Ethanol lock and risk of hemodialysis catheter infection in critically ill patients. A randomized controlled trial. Am J Respir Crit Care Med. 2015;191:1024–1032. doi: 10.1164/rccm.201408-1431OC.
    1. Ashouri OS. Regional sodium citrate anticoagulation in patients with active bleeding undergoing hemodialysis. Uremia Invest. 1985;9:45–51. doi: 10.3109/08860228509104839.
    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;24:208–211. doi: 10.1177/039139880102400407.
    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;3:369–374. 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;53:1034–1041. doi: 10.1053/j.ajkd.2009.01.259.
    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;63:479–490. doi: 10.1053/j.ajkd.2013.08.016.
    1. Weijmer MC, van den Dorpel MA, Van de Ven PJ, ter Wee PM, van Geelen JA, 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;16:2769–2777. doi: 10.1681/ASN.2004100870.
    1. Cardinal P, Allan J, Pham B, Hindmarsh T, Jones G, Delisle S. The effect of sodium citrate in arterial catheters on acid-base and electrolyte measurements. Crit Care Med. 2000;28:1388–1392. doi: 10.1097/00003246-200005000-00021.
    1. Flanigan MJ, Von Brecht J, Freeman RM, Lim VS. Reducing the hemorrhagic complications of hemodialysis: a controlled comparison of low-dose heparin and citrate anticoagulation. Am J Kidney Dis. 1987;9:147–153. doi: 10.1016/S0272-6386(87)80092-6.
    1. Polaschegg HD, Sodemann K. Risks related to catheter locking solutions containing concentrated citrate. Nephrol Dial Transplant. 2003;18:2688–2690. doi: 10.1093/ndt/gfg481.
    1. Bruyere R, Soudry-Faure A, Capellier G, Binquet C, Nadji A, Torner S, et al. Comparison of heparin to citrate as a catheter locking solution for non-tunneled central venous hemodialysis catheters in patients requiring renal replacement therapy for acute renal failure (VERROU-REA study): study protocol for a randomized controlled trial. Trials. 2014;15:449. doi: 10.1186/1745-6215-15-449.
    1. Le Gall JR, Lemeshow S, Saulnier F. A new simplified acute physiology score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270:2957–2963. doi: 10.1001/jama.1993.03510240069035.
    1. Vascular Access Work G Clinical practice guidelines for vascular access. Am J Kidney Dis. 2006;48(Suppl 1):S176–S247.
    1. Hermite L, Quenot JP, Nadji A, Barbar SD, Charles PE, Hamet M, et al. Sodium citrate versus saline catheter locks for non-tunneled hemodialysis central venous catheters in critically ill adults: a randomized controlled trial. Intensive Care Med. 2012;38:279–285. doi: 10.1007/s00134-011-2422-y.
    1. Moran JE, Ash SR. Locking solutions for hemodialysis catheters; heparin and citrate–a position paper by ASDIN. Semin Dial. 2008;21:490–492. 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;25:1753–1756. doi: 10.1093/ndt/gfq205.
    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;23:3592–3598. 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;21:2247–2255. doi: 10.1093/ndt/gfl170.
    1. Parienti JJ, Deryckere S, Megarbane B, Valette X, Seguin A, Sauneuf B, et al. Quasi-experimental study of sodium citrate locks and the risk of acute hemodialysis catheter infection among critically ill patients. Antimicrob Agents Chemother. 2014;58:5666–5672. doi: 10.1128/AAC.03079-14.
    1. Grudzinski A, Agarwal A, Bhatnagar N, Nesrallah G. Benefits and harms of citrate locking solutions for hemodialysis catheters: a systematic review and meta-analysis. Can J Kidney Health Dis. 2015;2:13. doi: 10.1186/s40697-015-0040-2.

Source: PubMed

赞助者和合作者

医疗条件

药物干预

3
订阅