Version May 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 continuous renal replacement therapy circuit (off-label use): Note: Citrate solution 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). Safety: According to the manufacturer, use is contraindicated in patients likely to have impaired citrate clearance (eg, acute liver failure with transaminases >1,000 units/L); however, if necessary, may be used with close monitoring and appropriate adjustments (Ref). When regional citrate anticoagulation is utilized, calcium is lost in the dialysis effluent in the form of citrate-calcium complexes. Calcium repletion must be administered to avoid hypocalcemia. Calcium may be infused at the end of the dialysis circuit or IV through a separate central line (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 1.4 mg/dL (0.25 to 0.35 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. Considered contraindicated in patients with acute liver failure and blood transaminase values >1,000 units/L; however, if necessary, may be used with close monitoring and appropriate adjustments (Davenport 2021; Meersch 2018).
• Shock states: Use with caution in patients with shock and hypoperfusion; may accumulate with hypoperfusion/shock states leading to toxicity. Considered contraindicated in patients with cardiogenic shock and blood lactate concentrations >8 mmol/L (Davenport 2021).
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
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
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 2021; KDIGO 2012).
Citrate 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).
Citrate ions induce anticoagulation by chelating free ionized calcium, making it unavailable for use in the coagulation system.
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