Skip to main content

Optimizing citrate dose for regional anticoagulation in continuous renal replacement therapy: measuring citrate concentrations instead of ionized calcium?

Regular measurement of systemic and post-filter ionized calcium (iCa) concentrations is imperative to correctly handle regional citrate anticoagulation dose during continuous renal replacement therapy (CRRT). Keeping post-filter iCa within a tight range guarantees optimal circuit function and enhances filter life span [1, 2], whereas a decrease in plasma iCa, with subsequent elevation of the total-to-ionized plasma calcium ratio, can predict systemic citrate accumulation [3].

The new findings (published recently in Critical Care) of Schwarzer et al. expose an alarming inaccuracy for measuring post-filter iCa with currently available blood gas analyzers [4]. This precludes adequate control of citrate flow and raises evident functional and safety issues. On the other hand, Schwarzer et al. found good concordance between all evaluated analyzers for measuring systemic iCa levels [4]. However, the total-to-ionized plasma calcium ratio has occasionally been shown to be a relatively weak indirect marker for citrate accumulation or intoxication [1, 2]. Direct measurement of citrate systemic concentrations could overcome these iCa-related shortcomings. In this perspective, compelling evidence was provided by Italian investigators who adapted a commercially available citrate analyzing kit for measuring systemic and also filter citrate concentrations [5]. Preliminary experience in septic shock patients with liver dysfunction undergoing CRRT suggested a potential clinical use but needs confirmation in a larger and more heterogeneous patient population.



Continuous renal replacement therapy


Ionized calcium


  1. Egi M, Naka T, Bellomo R, Cole L, French C, Trethewy C, et al. A comparison of two citrate anticoagulation regimens for continuous veno-venous hemofiltration. Int J Artif Organs. 2005;28:1211–8.

    Article  CAS  Google Scholar 

  2. Jacobs R, Honoré PM, Bagshaw SM, Diltoer M, Spapen HD. Citrate formulation determines filter lifespan during continuous veno-venous hemofiltration: a prospective cohort study. Blood Purif. 2015;40:194–202.

    Article  CAS  Google Scholar 

  3. Meier-Kriesche HU, Gitomer J, Finkel K, DuBose T. Increased total to ionized calcium ratio during continuous venovenous hemodialysis with regional citrate anticoagulation. Crit Care Med. 2001;29:748–52.

    Article  CAS  Google Scholar 

  4. Schwarzer P, Kuhn SO, Stracke S, Gründling M, Knigge S, Selleng S, et al. Discrepant post filter ionized calcium concentrations by common blood gas analyzers in CRRT using regional citrate anticoagulation. Crit Care. 2015;19:321.

    Article  Google Scholar 

  5. Mariano F, Morselli M, Bergamo D, Hollo Z, Scella S, Maio M, et al. Blood and ultrafiltrate dosage of citrate as a useful and routine tool during continuous venovenous haemodiafiltration in septic shock patients. Nephrol Dial Transplant. 2011;26:3882–8.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Corresponding author

Correspondence to Patrick M. Honore.

Additional information

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

PMH and HDS designed and helped draft the manuscript. RJ, IH, EDW and VVG helped draft the manuscript. All authors read and approved the final manuscript.

See related research by Schwarzer et al.,

Rights and permissions

Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (, which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Honore, P.M., Jacobs, R., Hendrickx, I. et al. Optimizing citrate dose for regional anticoagulation in continuous renal replacement therapy: measuring citrate concentrations instead of ionized calcium?. Crit Care 19, 386 (2015).

Download citation

  • Published:

  • DOI: