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Continuous dialysis · Regional citrate anticoagulation

Citrate kinetics on CRRT

How much citrate does the patient keep? Enter the CVVHDF prescription to get citrate load and worst-case accumulation, then project systemic citrate by liver clearance, including a sudden loss of liver metabolism. Read the reference.

1Prescription and steady state

Citrate infused before the filter is partly removed in the effluent on the same pass; the rest returns to the patient as the citrate load. At steady state, citrate load equals removal.

Lenar Yessayan, MD · Sevag Demirjian, MD

Modality

Blood side

mL/min
g/dL
mL/hr
mmol/L

Effluent side

L/hr
L/hr
L/hr
Effluent QEFF2.90 L/hr

Results

Patient citrate load Gdose × (1 − Ecit)20.4mmol/hr
Worst-case CMaxNo liver metabolism · G ÷ Kf7.33mmol/L
Citrate dose33.9mmol/hr
Plasma flow Qp6.98L/hr
Extraction Ecit0.40
Dialyzer Kf2.78L/hr
Removed in effluent13.5mmol/hr
Hematocrit22.5%

Load = removal

Ecit = 0.40 CRRT intake Qp × C Citrate infusion 33.9 mmol/h Effluent 13.5 mmol/h Patient load G 20.4 mmol/h

CMax = [QACDA × CACDA ÷ (QB × (1 − Hct/100))] × (1 − Ecit) ÷ Ecit
The first term is fixed by the ACD-A : blood-flow ratio. The second depends on how much circuit plasma passes into effluent.

Ecit ≈

2Systemic citrate by liver clearance

Single-pool, fixed-volume model: citrate enters at load G and leaves by the dialyzer (Kf) and by body, mainly liver, metabolism (Kb). Uses the prescription above.

Patient

L
L
mmol/L

Projection

L/hr
hours

C(t) = C(0)·e−(Kf+Kb)t/V + G/(Kf+Kb) · (1 − e−(Kf+Kb)t/V)

Fair 15 L/hWeak 6 L/hAbsent 0 L/hPatient

Fair ≈ usual liver function, including compensated cirrhosis. Weak ≈ severely impaired but enough to avoid toxicity. Dashed verticals mark iCa checks at 2, 4 and 6 h.

Liver clearance2 h4 h6 h12 hSteady state95% of SS

mmol/L. Values ≥ 2.5 mmol/L are in red: the range where accumulation becomes a clinical concern (rising total/ionized calcium ratio).

3Sudden loss of liver clearance

Liver citrate metabolism can stop abruptly: cardiac arrest, refractory shock, acute liver failure. Compare the prescription above with a high-extraction alternative when Kb falls mid-run.

Event

L/hr
hour
L/hr
hours

Alternative CVVHDF prescription

mL/min
mL/hr
L/hr
L/hr
L/hr

Same hemoglobin, ACD-A concentration, saturation and volume as above. An editable illustration, not a protocol.

Alternative Ecit—target > 0.75
Alternative load G—mmol/hr
Alternative CMax—target < 2.5
Current prescriptionAlternative2.5 mmol/L
PrescriptionBefore eventEndCMaxTo 2.5 after event

Clinical pearls

  • Accumulation is a prescription problem first. CMax depends only on the ACD-A : QB ratio, hematocrit and Ecit. Liver clearance decides how far below CMax the patient settles.
  • Timing of detection. With fair clearance, citrate plateaus within about 3 to 4 h. With absent clearance it is still rising at 12 h, so an early normal total/ionized calcium ratio does not exclude later accumulation.
  • Shock settings. Lowering QB while keeping effluent high pushes Ecit above about 0.75 and keeps CMax below about 2.5 mmol/L even with no liver metabolism, so accumulation is self-limited.
  • CVVHD vs CVVHDF. Citrate is small (about 190 Da), so diffusion and convection clear it about equally while dialysate stays saturated. In CVVHD all extraction comes from dialysate; at high QD relative to blood flow, saturation falls below 1 and Ecit levels off (lower SD to see the effect). CVVHDF adds post-filter replacement, which raises effluent without relying on diffusion.
  • Edema changes speed, not the plateau. A larger V slows the approach to steady state but does not change the steady-state level.

Model notes: Single-pool, fixed-volume kinetic equation (Szamosfalvi et al.; validated by Zheng), as applied in Yessayan et al., BMC Nephrology 2021. Ecit is estimated as clearance-effective effluent (QD × SD + QRF + net UF + QACDA) ÷ (plasma flow + ACD-A flow), assuming citrate sieving ≈ 1 and post-dilution replacement; QRF is zero in CVVHD. Real extraction is lower with filter clotting or unsaturated dialysate. Hct ≈ Hb × 3. Calcium infusion volume and citrate–calcium complex losses are ignored. Defaults reproduce the paper’s non-shock example (QB 150 mL/min, ACD-A 300 mL/h, QD/QRF 1.2 L/h, net UF 0.2 L/h, Hb 7.5 g/dL, ECF 15 L + 7 L edema).

Clinical disclaimer — read before using

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