Version August 2024
Note: 4% trisodium citrate has a sodium content of 408 mmol/L. To avoid severe hypernatremia, protocols typically employ lower sodium dialysate and/or replacement fluids and titrate accordingly (Ref). Refer to institutional protocols.
Regional anticoagulation for CRRT circuit (off-label use): Note: Must only be prescribed and administered by trained personnel, as standardized (and often specialized) dialysate and/or replacement fluids and titration and monitoring protocols are required (Ref). Citrate solution is administered through the inflow (prefilter or “arterial”) limb of the extracorporeal CRRT circuit, not administered directly to the patient (Ref). Due to the loss of citrate-calcium complexes in dialysis effluent, calcium repletion must be administered at the end of the dialysis circuit or IV through a separate central line to avoid hypocalcemia (Ref). Safety: Avoid or use with extreme caution and special protocols in patients with impaired citrate clearance (eg, hyperacute liver failure [ie, within 7 days] with blood transaminase >1,000 units/L or cardiogenic shock with blood lactate concentrations >8 mmol/L) (Ref).
Example regimen:
Initial infusion rate (in mL/hour): Intracircuit: Use a 4% trisodium citrate dihydrate solution: Approximate usual initial infusion rate: ~1 to 1.5 times the blood flow rate; for example, if blood flow rate is 100 to 200 mL/minute, start infusion at 100 to 300 mL/hour (Ref). Optimal 4% trisodium regimens have not been identified; refer to institutional protocols as variations exist. Adjustment of 4% trisodium citrate and calcium infusion rates is dependent on established protocols and ionized calcium concentrations.
CRRT calcium: Monitor ionized calcium concentrations in outflow (postfilter) limb of the CRRT circuit; maintain CRRT circuit iCa between 1 to 1.6 mg/dL (0.25 to 0.4 mmol/L) (Ref).
Serum calcium: Monitor systemic iCa concentration peripherally (drawn directly from the patient) and maintain systemic iCa between 3.6 to 4.8 mg/dL (0.9 to 1.2 mmol/L) (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Frequency not defined:
Cardiovascular: Cardiac arrhythmia, chest pressure, hypotension
Central nervous system: Chills, paresthesia, tingling in the lips, tingling of extremities
Gastrointestinal: Stomach cramps
Do not administer to a patient by direct IV infusion.
Disease-related concerns:
• Hepatic impairment: Use with caution in patients with liver impairment. Citrate is partially metabolized by the liver and may accumulate with hepatic impairment leading to toxicity. When used for regional anticoagulation of the CRRT circuit, anticoagulant sodium citrate is considered relatively contraindicated in patients with hyperacute liver failure (ie, within 7 days) with blood transaminase values >1,000 units/L; however, if necessary, may be used with close monitoring and appropriate adjustments (Davenport 2024; Meersch 2018; Szamosfalvi 2020).
• Shock states: Use with caution in patients with shock and hypoperfusion; may accumulate with hypoperfusion/shock states leading to toxicity. When used for regional anticoagulation of the CRRT circuit, anticoagulant sodium citrate is considered relatively contraindicated in patients with cardiogenic shock with blood lactate concentrations >8 mmol/L (Davenport 2024).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Concentrate, In Vitro:
TriCitrasol: 46.7% (30 mL)
Solution, In Vitro:
Generic: 4% (250 mL, 500 mL)
May be product dependent
Concentrate (TriCitrasol In Vitro)
46.7% (per mL): $0.30
Solution (Anticoagulant Sodium Citrate In Vitro)
4% (per mL): $0.05
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Liquid, In Vitro:
Generic: 4% (250 mL)
Solution, In Vitro:
Generic: 4% (250 mL)
Anticoagulant:
Concentrate (triCitrasol): Anticoagulant used in granulocytapheresis procedures
Solution: Anticoagulant for use with cytapheresis device only
Regional anticoagulation for continuous renal replacement therapy circuit
Anticoagulant sodium citrate may be confused with anticoagulant citrate dextrose
None known.
There are no known significant interactions.
When used for regional anticoagulation of the CRRT circuit: Monitor serum electrolytes ~15 minutes and 1 hour after starting CRRT, then at least every 6 hours for CRRT; particularly monitor iCa, sodium, potassium, chloride, magnesium, and bicarbonate to avoid metabolic abnormalities; acid-base balance; anion gap; for CRRT monitor total body calcium at least once daily to calculate the calcium ratio (total calcium/iCa) (calcium ratio may indicate citrate toxicity if >2.1); monitoring post-filter iCa may be beneficial to ensure adequate anticoagulation of the dialysis circuit (Davenport 2024; KDIGO 2012).
Citrate overload or accumulation may be managed by decreasing the blood flow rate (which decreases citrate requirements), increasing the dialysate rate (CVVHD) or the filtration rate (CVVH) to increase removal, or decreasing the targeted citrate concentration within the filter (Schneider 2017). In cases where adjustments do not rapidly correct accumulation, regional citrate anticoagulation should be discontinued and replaced with alternative circuit anticoagulation (Davenport 2024; Schneider 2017).
Citrate ions induce anticoagulation by chelating free ionized calcium, making it unavailable for use in the coagulation system.
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