Case 44: Diagnosis & Conclusions

Case 44 Index

Diagnosis: Citrate Toxicity

Case Summary: Great work! Let’s review this case.

Here we have a critically ill patient who developed acute kidney injury requiring continuous kidney replacement therapy (CKRT). The patient was started on continuous veno-venous hemofiltration (CVVH) for solute clearance with regional citrate anticoagulation (RCA). Citrate is considered an effective anticoagulant because of its ability to bind ionized calcium in the blood. Calcium is necessary for the formation of several clotting factors (factors II, IX, X, XI). When citrate chelates ionized calcium, it reduces the ability of the clotting cascade to occur, since less calcium is available for factor formation. 

Citrate can be administered in combination with replacement fluid or as a separate solution. Two varieties of solutions used for RCA are anticoagulant citrate dextrose solution (ACD-A) and 4% trisodium citrate solution (TCA). As both have a higher sodium concentration then 0.9% normal saline, accompanying replacement fluid or dialysate should have lower sodium concentrations to avoid hypernatremia. 

In our patient, the cartridge clots twice within the first 24 hours. To determine how effectively the circuit has been anticoagulated, we  can measure post-filter ionized calcium levels. Our patient’s post-filter ionized calcium is 0.6 mmol/L. Ionized calcium levels > 0.4 mmol/L suggest that anticoagulation is  inadequate – which likely explains why this patient’s cartridge experiences recurrent clotting. Based on these findings, the the RCA infusion rate should be increased.

Let’s also calculate the filtration fraction (FF).  The FF is the ratio of the rate of fluid REMOVAL across a filter to the rate of fluid ENTERING the filter. Thus, an elevated filtration fraction also places the patient at higher risk of clotting (increased fluid removal increases the FF while increasing the rate of fluid entering the filter decreases it).  Of note, dialysate is NOT a part of the FF calculation and should not be included for patients on CVVHD or CVVHDF). 

For our patient, the ultrafiltration rate will be 2L/hr (assuming 2L/hr replacement fluid therapy rate without additional ultrafiltration). The blood flow rate is 250 mL/min and the hematocrit is 28%. Note that in this case, citrate was added directly to the replacement fluid. If citrate is administered as a separate infusion, this rate should be added to the ultrafiltration rate. Let’s crunch the numbers below (or do it yourself here!)


A FF of 16% is within the recommended < 20-25% range. After an increase in the rate of RCA administration, we notice the patient develops significant changes in his laboratory values… below is a summary of electrolyte and acid-base disturbances to look out for in patient’s receiving RCA.

Citrate Tox

To wrap things up, let’s calculate our patient’s total to ionized calcium ratio:
Total Ca 10.2 mg/dL = 2.55 mmol/L
Ionized Ca 0.8 mmol/L

This patient’s total calcium to ionized calcium ratio is 3.2 (>2.5), consistent with citrate toxicity!

Thank you to Neil Agarwal, MD from @PennKidney for this great case!

Check out a few helpful references below:

  1. Morabito, Santo et al. “Regional citrate anticoagulation for RRTs in critically ill patients with AKI.” Clinical journal of the American Society of Nephrology : CJASN vol. 9,12 (2014): 2173-88. doi:10.2215/CJN.01280214
  2. Honore, Patrick M et al. “Citrate: How to Get Started and What, When, and How to Monitor?.” Journal of translational internal medicine vol. 6,3 115-127. 9 Oct. 2018, doi:10.2478/jtim-2018-0026
  3. Hatamizadeh, Parta et al. “Revisiting Filtration Fraction as an Index of the Risk of Hemofilter Clotting in Continuous Venovenous Hemofiltration.” Clinical journal of the American Society of Nephrology : CJASN, CJN.02410220. 13 May. 2020, doi:10.2215/CJN.02410220
  4. Davenport, Andrew, and Ashita Tolwani. “Citrate anticoagulation for continuous renal replacement therapy (CRRT) in patients with acute kidney injury admitted to the intensive care unit.” NDT plus vol. 2,6 (2009): 439-47. doi:10.1093/ndtplus/sfp136

Case Published: June 2020

Case 44 Index
Case 44 Introduction
Case 44 Physical Exam
Case 44 Diagnostic Testing
Case 44 Next Steps
Case 44 Additional Diagnostic Testing