Complications of regional citrate anticoagulation: accumulation or overload?

Antoine G Schneider, Didier Journois, Thomas Rimmelé, Antoine G Schneider, Didier Journois, Thomas Rimmelé

Abstract

Regional citrate anticoagulation (RCA) is now recommended over systemic heparin for continuous renal replacement therapy in patients without contraindications. Its use is likely to increase throughout the world. However, in the absence of citrate blood level monitoring, the diagnosis of citrate accumulation, the most feared complication of RCA, remains relatively complex. It is therefore commonly mistaken with other conditions. This review aims at providing clarifications on RCA-associated acid-base disturbances and their management at the bedside. In particular, the authors wish to propose a clear distinction between citrate accumulation and net citrate overload.

Keywords: Acute kidney injury; Citrate accumulation; Complications of therapy; Continuous renal replacement therapy; Metabolic alkalosis; Regional citrate anticoagulation.

Conflict of interest statement

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

AS received speaker honoraria from Fresenius Medical Care and Baxter Healthcare Corp. and consulting honoraria from B. Braun Melsungen AG. DJ has no competing interests to disclose. TR received speaker honoraria from Fresenius Medical Care, Baxter Healthcare Corp., and Bellco-Medtronic.

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Figures

Fig. 1
Fig. 1
“ON-OFF” anticoagulation effect of ionized hypocalcemia. The grey zone corresponds to the area of adequate anticoagulation. Target values indicated are only indicative and depend on the protocol used [12]
Fig. 2
Fig. 2
Schematic view of a CRRT circuit with regional citrate administration in CVVHD mode. Alternative modes can be used (postdilution CVVH, combined pre- and postdilution CVVH, CVVHDF, etc.) according to the protocol used. Citrate solution is administered at the beginning of the CRRT circuit. It forms citrate–calcium complexes, which are largely removed from the blood at the level of the filter. Only complexes which are not removed through the hemofilter return to the patient’s blood and need to be metabolized
Fig. 3
Fig. 3
Citrate calcium complex. The distance between calcium’s two positive charges corresponds to the distance between two citrate carboxylate radicals. A carboxylate radical remains unbound, providing residual anionic charge and a mild acidic effect. This acidifying effect would be much stronger in vitro, in the absence of ionized calcium
Fig. 4
Fig. 4
Theoretical relationship between blood citrate level and citrate load. a An increase in citrate load is not associated with an increase in blood citrate level until a threshold is reached. This threshold corresponds to the body’s capacity to metabolize citrate. b Certain circumstances, such as severe liver failure or circulatory shock, might result in a lower threshold corresponding to a decreased capacity to metabolize citrate (see text)
Fig. 5
Fig. 5
Consequences of citrate accumulation

References

    1. Uchino S, Bellomo R, Morimatsu H, Morgera S, Schetz M, Tan I, Bouman C, Macedo E, Gibney N, Tolwani A, 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(9):1563–70. doi: 10.1007/s00134-007-0754-4.
    1. Joannidis M, Oudemans-van Straaten HM. Patency of the circuit in continuous renal replacement therapy. Crit Care. 2007;11(4):218. doi: 10.1186/cc5937.
    1. Mehta RL, McDonald BR, Aguilar MM, Ward DM. Regional citrate anticoagulation for continuous arteriovenous hemodialysis in critically ill patients. Kidney Int. 1990;38(5):976–81. doi: 10.1038/ki.1990.300.
    1. Stucker F, Ponte B, Tataw J, Martin PY, Wozniak H, Pugin J, Saudan P. 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. Crit Care. 2015;19:91. doi: 10.1186/s13054-015-0822-z.
    1. Gattas DJ, Rajbhandari D, Bradford C, Buhr H, Lo S, Bellomo R. A randomized controlled trial of regional citrate versus regional heparin anticoagulation for continuous renal replacement therapy in critically ill adults. Crit Care Med. 2015;43(8):1622–9. doi: 10.1097/CCM.0000000000001004.
    1. Schilder L, Nurmohamed SA, Bosch FH, Purmer IM, den Boer SS, Kleppe CG, Vervloet MG, Beishuizen A, Girbes AR, Ter Wee PM, 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(4):472. doi: 10.1186/s13054-014-0472-6.
    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(1):20–8. doi: 10.1007/s00134-011-2438-3.
    1. Bai M, Zhou M, He L, Ma F, Li Y, Yu Y, Wang P, Li L, Jing R, Zhao L, et al. Citrate versus heparin anticoagulation for continuous renal replacement therapy: an updated meta-analysis of RCTs. Intensive Care Med. 2015;41(12):2098–110. doi: 10.1007/s00134-015-4099-0.
    1. Khadzhynov D, Schelter C, Lieker I, Mika A, Staeck O, Neumayer HH, Peters H, Slowinski T. Incidence and outcome of metabolic disarrangements consistent with citrate accumulation in critically ill patients undergoing continuous venovenous hemodialysis with regional citrate anticoagulation. J Crit Care. 2014;29(2):265–71. doi: 10.1016/j.jcrc.2013.10.015.
    1. KDIGO Kidney disease: improving global outcomes (KDIGO) acute kidney injury work group (2012) KDIGO clinical practice guidelines AKI: AKI definition. Kidney Int. 2012;2(1):19–36. doi: 10.1038/kisup.2011.32.
    1. James MF, Roche AM. Dose-response relationship between plasma ionized calcium concentration and thrombelastography. J Cardiothorac Vasc Anesth. 2004;18(5):581–6. doi: 10.1053/j.jvca.2004.07.016.
    1. Calatzis A, Toepfer M, Schramm W, Spannagl M, Schiffl H. Citrate anticoagulation for extracorporeal circuits: effects on whole blood coagulation activation and clot formation. Nephron. 2001;89(2):233–6. doi: 10.1159/000046075.
    1. Morgera S, Schneider M, Slowinski T, Vargas-Hein O, Zuckermann-Becker H, Peters H, Kindgen-Milles D, Neumayer HH. A safe citrate anticoagulation protocol with variable treatment efficacy and excellent control of the acid-base status. Crit Care Med. 2009;37(6):2018–24. doi: 10.1097/CCM.0b013e3181a00a92.
    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(1):79–87. doi: 10.2215/CJN.00040505.
    1. Balik M, Zakharchenko M, Otahal M, Hruby J, Polak F, Rusinova K, Stach Z, Vavrova J, Jabor A. Quantification of systemic delivery of substrates for intermediate metabolism during citrate anticoagulation of continuous renal replacement therapy. Blood Purif. 2012;33(1-3):80–7. doi: 10.1159/000334641.
    1. Balik M, Zakharchenko M, Leden P, Otahal M, Hruby J, Polak F, Rusinova K, Stach Z, Tokarik M, Vavrova J, et al. Bioenergetic gain of citrate anticoagulated continuous hemodiafiltration--a comparison between 2 citrate modalities and unfractionated heparin. J Crit Care. 2013;28(1):87–95. doi: 10.1016/j.jcrc.2012.06.003.
    1. Stewart PA. Modern quantitative acid-base chemistry. Can J Physiol Pharmacol. 1983;61(12):1444–61. doi: 10.1139/y83-207.
    1. Adrogue HJ, Madias NE. Assessing acid-base status: physiologic versus physicochemical approach. Am J Kidney Dis. 2016;68(5):793–802. doi: 10.1053/j.ajkd.2016.04.023.
    1. Nagaoka D, Nassar Junior AP, Maciel AT, Taniguchi LU, Noritomi DT, Azevedo LC, Neto LM, Park M. The use of sodium-chloride difference and chloride-sodium ratio as strong ion difference surrogates in the evaluation of metabolic acidosis in critically ill patients. J Crit Care. 2010;25(3):525–31. doi: 10.1016/j.jcrc.2010.02.003.
    1. Goldberg RNKN, Lennen RM. Thermodynamic quantities for the ionization reactions of buffers. J Phys Chem Ref Data. 2002;31(2):231–370. doi: 10.1063/1.1416902.
    1. Schultheiss C, Saugel B, Phillip V, Thies P, Noe S, Mayr U, Haller B, Einwachter H, Schmid RM, Huber W. Continuous venovenous hemodialysis with regional citrate anticoagulation in patients with liver failure: a prospective observational study. Crit Care. 2012;16(4):R162. doi: 10.1186/cc11485.
    1. Slowinski T, Morgera S, Joannidis M, Henneberg T, Stocker R, Helset E, Andersson K, Wehner M, Kozik-Jaromin J, Brett S, et al. Safety and efficacy of regional citrate anticoagulation in continuous venovenous hemodialysis in the presence of liver failure: the Liver Citrate Anticoagulation Threshold (L-CAT) observational study. Crit Care. 2015;19:349. doi: 10.1186/s13054-015-1066-7.
    1. De Vico P, Messino V, Tartaglione A, Beccaris C, Buonomo C, Talarico D, Prati P, Sabato AF, Colella DF. Safety and efficacy of citrate anti-coagulation continuous renal replacement therapies in post-cardiac surgery patients with liver dysfunction. Ther Apher Dial. 2015;19(3):272–8. doi: 10.1111/1744-9987.12280.
    1. Oudemans-van Straaten HM, Kellum JA, Bellomo R. Clinical review: anticoagulation for continuous renal replacement therapy--heparin or citrate? Crit Care. 2011;15(1):202. doi: 10.1186/cc9358.

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