Efficacy and safety of citrate-based anticoagulation compared to heparin in patients with acute kidney injury requiring continuous renal replacement therapy: a randomized controlled trial

Fabien Stucker, Belen Ponte, James Tataw, Pierre-Yves Martin, Hannah Wozniak, Jérome Pugin, Patrick Saudan, Fabien Stucker, Belen Ponte, James Tataw, Pierre-Yves Martin, Hannah Wozniak, Jérome Pugin, Patrick Saudan

Abstract

Introduction: A systemic anticoagulation is often required to prevent circuit and filter clotting in ICU patients undergoing continuous renal replacement therapy (CRRT). A regional citrate-based anticoagulation (RCA) does not induce a systemic anticoagulation and prolongs the filter lifespan, but metabolic side-effects have been associated with this therapy. We conducted a randomized controlled trial with patients requiring CRRT to determine whether RCA using a balanced predilution replacement fluid is more effective than heparin in terms of renal replacement delivered dose and safety profile.

Methods: One hundred and three patients with AKI requiring CRRT were included. The patients were randomized to either CRRT with RCA or heparin anticoagulation. Primary endpoints were effective daily delivered RRT dose during the first 3 days of CRRT and filter lifespan. Secondary endpoints were 28-day and 90-day survival and severe metabolic complications and bleeding disorders.

Results: Median CRRT duration was 3.0 (2-6) days. Effective delivered daily RRT doses were 29 ± 3 and 27 ± 5 mL/kg/hr in the RCA and heparin groups, respectively (p = 0.005). Filter lifespans were 49 ± 29 versus 28 ± 23 hrs in the RCA and heparin groups (p = 0.004). Survival rates at 28 and 90 days were 80-74% in the RCA and 74-73% in the heparin group. Electrolytes and acid-base disturbances were uncommon and transient in patients treated with RCA.

Conclusions: These results show that RCA is superior to heparin-based anticoagulation in terms of delivered RRT dose and filter life span and is a safe and feasible method. This does not translate into an improvement in short term survival.

Trial registration: ClinicalTrials.gov NCT01269112 . Registered 3rd January 2011.

Figures

Figure 1
Figure 1
Flow chart of the trial.
Figure 2
Figure 2
Kaplan-Meier analysis of the filter lifespan.

References

    1. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, et al. Acute renal failure in critically ill patients: a multinational, multicenter study. Jama. 2005;294:813–818. doi: 10.1001/jama.294.7.813.
    1. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, et al. Continuous renal replacement therapy: a worldwide practice survey. The beginning and ending supportive therapy for the kidney (B.E.S.T. kidney) investigators. Intensive Care Med. 2007;33:1563–1570. doi: 10.1007/s00134-007-0754-4.
    1. Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy–heparin or citrate? Crit Care. 2011;15:202. doi: 10.1186/cc9358.
    1. Tolwani AJ, Prendergast MB, Speer RR, Stofan BS, Wille KM. A practical citrate anticoagulation continuous venovenous hemodiafiltration protocol for metabolic control and high solute clearance. Clin J Am Soc Nephrol. 2006;1:79–87. doi: 10.2215/CJN.00040505.
    1. Monchi M, Berghmans D, Ledoux D, Canivet JL, Dubois B, Damas P. Citrate vs. heparin for anticoagulation in continuous venovenous hemofiltration: a prospective randomized study. Intensive Care Med. 2004;30:260–265. doi: 10.1007/s00134-003-2047-x.
    1. Dorval M, Madore F, Courteau S, Leblanc M. A novel citrate anticoagulation regimen for continuous venovenous hemodiafiltration. Intensive Care Med. 2003;29:1186–1189. doi: 10.1007/s00134-003-1801-4.
    1. Morgera S, Scholle C, Voss G, Haase M, Vargas-Hein O, Krausch D, et al. Metabolic complications during regional citrate anticoagulation in continuous venovenous hemodialysis: single-center experience. Nephron Clin Pract. 2004;97:c131–c136. doi: 10.1159/000079171.
    1. Schilder L, Nurmohamed SA, Bosch FH, Purmer IM, den Boer SS, Kleppe CG, et al. Citrate anticoagulation versus systemic heparinisation in continuous venovenous hemofiltration in critically ill patients with acute kidney injury: a multi-center randomized clinical trial. Crit Care. 2014;18:472. doi: 10.1186/s13054-014-0472-6.
    1. Morabito S, Pistolesi V, Tritapepe L, Vitaliano E, Zeppilli L, Polistena F, et al. Continuous venovenous hemodiafiltration with a low citrate dose regional anticoagulation protocol and a phosphate-containing solution: effects on acid–base status and phosphate supplementation needs. BMC Nephrol. 2013;14:232. doi: 10.1186/1471-2369-14-232.
    1. Oudemans-van Straaten HM, Bosman RJ, Koopmans M, van der Voort PH, Wester JP, van der Spoel JI, et al. Citrate anticoagulation for continuous venovenous hemofiltration. Crit Care Med. 2009;37:545–552. doi: 10.1097/CCM.0b013e3181953c5e.
    1. Hetzel GR, Schmitz M, Wissing H, Ries W, Schott G, Heering PJ, et al. Regional citrate versus systemic heparin for anticoagulation in critically ill patients on continuous venovenous haemofiltration: a prospective randomized multicentre trial. Nephrol Dial Transplant. 2011;26:232–239. doi: 10.1093/ndt/gfq575.
    1. Lameire N, Kellum JA. Contrast-induced acute kidney injury and renal support for acute kidney injury: a KDIGO summary (Part 2) Crit Care. 2013;17:205. doi: 10.1186/cc11455.
    1. Bellomo R, Kellum JA, Ronco C. Defining and classifying acute renal failure: from advocacy to consensus and validation of the RIFLE criteria. Intensive Care Med. 2007;33:409–413. doi: 10.1007/s00134-006-0478-x.
    1. Bellomo R, Cass A, Cole L, Finfer S, Gallagher M, Lo S, et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009;361:1627–1638. doi: 10.1056/NEJMoa0902413.
    1. Mehta RL, McDonald BR, Aguilar MM, Ward DM. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int. 1990;38:976–981. doi: 10.1038/ki.1990.300.
    1. Morabito S, Pistolesi V, Tritapepe L, Fiaccadori E. Regional citrate anticoagulation for RRTs in critically ill patients with AKI. Clin J Am Soc Nephrol. 2014;9:2173–2188. doi: 10.2215/CJN.01280214.
    1. Joannidis M, Oudemans-van Straaten HM. Clinical review: Patency of the circuit in continuous renal replacement therapy. Crit Care. 2007;11:218. doi: 10.1186/cc5937.
    1. Venkataraman R, Kellum JA. Defining acute renal failure: the RIFLE criteria. J Intensive Care Med. 2007;22:187–193. doi: 10.1177/0885066607299510.
    1. Zhang Z, Hongying N. Efficacy and safety of regional citrate anticoagulation in critically ill patients undergoing continuous renal replacement therapy. Intensive Care Med. 2012;38:20–28. doi: 10.1007/s00134-011-2438-3.
    1. Betjes MG, van Oosterom D, van Agteren M, van de Wetering J. Regional citrate versus heparin anticoagulation during venovenous hemofiltration in patients at low risk for bleeding: similar hemofilter survival but significantly less bleeding. J Nephrol. 2007;20:602–608.
    1. Kutsogiannis DJ, Gibney RT, Stollery D, Gao J. Regional citrate versus systemic heparin anticoagulation for continuous renal replacement in critically ill patients. Kidney Int. 2005;67:2361–2367. doi: 10.1111/j.1523-1755.2005.00342.x.
    1. Wu MY, Hsu YH, Bai CH, Lin YF, Wu CH, Tam KW. Regional citrate versus heparin anticoagulation for continuous renal replacement therapy: a meta-analysis of randomized controlled trials. Am J Kidney Dis. 2012;59:810–818. doi: 10.1053/j.ajkd.2011.11.030.
    1. Leung AK, Shum HP, Chan KC, Chan SC, Lai KY, Yan WW. A retrospective review of the use of regional citrate anticoagulation in continuous venovenous hemofiltration for critically ill patients. Crit Care Res Pract. 2013;2013:349512.
    1. Nurmohamed SA, Jallah BP, Vervloet MG, Yldirim G, ter Wee PM, Groeneveld AB. Continuous venovenous haemofiltration with citrate-buffered replacement solution is safe and efficacious in patients with a bleeding tendency: a prospective observational study. BMC Nephrol. 2013;14:89. doi: 10.1186/1471-2369-14-89.
    1. Schultheiss C, Saugel B, Phillip V, Thies P, Noe S, Mayr U, et al. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care. 2012;16:R162. doi: 10.1186/cc11485.

Source: PubMed

Sponsor e collaboratori

Condizioni mediche

Interventi farmacologici

3
Sottoscrivi