Dosage Forms
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)
Pharmacology
Mechanism of Action
Citrate ions induce anticoagulation by chelating free ionized calcium, making it unavailable for use in the coagulation system.
Use: Labeled Indications
Anticoagulant:
Concentrate (triCitrasol): Anticoagulant used in granulocytapheresis procedures
Solution: Anticoagulant for use with cytapheresis device only
Use: Off Label
Regional anticoagulation for continuous renal replacement therapy circuitbyes
Data from several small randomized, controlled trials support the use of regional anticoagulant sodium citrate to reduce the risk of clot formation in continuous renal replacement therapy (CRRT) circuits, thus prolonging circuit life and avoiding interruptions in therapy. It should be noted that patients with high bleeding risk, severe coagulopathy, metabolic abnormalities, or liver dysfunction were excluded from these trials Betjes 2007, Clark 2008, Gattas 2015, Hetzel 2011, Kutsogiannis 2005, Mitchell 2003, Monchi 2004, Morgera 2004, Oudemans-van Straaten 2009, Schilder 2014, Stucker 2015. A multicenter, prospective, observational study that included mild and severe liver failure demonstrated safe use of anticoagulant sodium citrate in patients with liver failure Slowinski 2015.
Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for acute kidney injury recommends anticoagulation of CRRT circuits. If a patient requires systemic, therapeutic anticoagulation for another indication, choose the most appropriate therapy. If no therapeutic anticoagulation is required, regional citrate anticoagulation is suggested over heparin. If there is an increased bleeding risk, regional citrate anticoagulation is still suggested over no anticoagulation. If a patient's coagulation is impaired, may consider using no anticoagulation for the CRRT circuit KDIGO 2012.
Contraindications
Do not administer to a patient by direct IV infusion.
Dosage and Administration
Dosing: Adult
Note: When regional citrate anticoagulation is utilized, calcium is lost in the dialysis effluent in the form of citrate-calcium complexes. Calcium repletion should be administered to avoid hypocalcemia. Calcium may be infused at the end of the dialysis circuit or IV through a separate central line. An optimal regimen has not been identified; refer to institutional protocols as variations exist (Davenport 2018; Schneider 2017).
Regional anticoagulation for continuous renal replacement therapy circuit (off-label use): Note: Citrate solution is administered through the inflow (prefilter or “arterial”) limb of the extracorporeal continuous renal replacement therapy (CRRT) circuit, not given directly to the patient. 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 (Davenport 2018; Meersch 2018; Slowinski 2015).
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 (Clark 2008; Davenport 2018; Morabito 2014; Morgera 2009). Adjust infusion rate accordingly based on circuit iCa monitoring:
If monitoring iCa concentration in outflow (post-filter) limb of the CRRT circuit: Adjust infusion rate to maintain CRRT circuit iCa between 1 to 1.4 mg/dL (0.25 to 0.35 mmol/L) (Clark 2008; Kutsogiannis 2000; Monchi 2004; Stucker 2015).
If monitoring systemic iCa concentration peripherally (drawn directly from the patient): Adjust infusion rate to maintain systemic iCa between 3.6 to 4.8 mg/dL (0.9 to 1.2 mmol/L) (Clark 2008; Gattas 2015).
Storage
Concentrate: Store at 24°C (75°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from freezing and excessive heat. Discard if solution becomes cloudy.
Solution: Store at room temperature. Do not remove from overlap until ready to use. Discard if solution becomes cloudy. Discard any unused portion.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Frequency not defined:
Cardiovascular: Cardiac arrhythmia, chest pressure, hypotension
Central nervous system: Chills, paresthesia, tingling in the lips, tingling of extremities
Gastrointestinal: Stomach cramps
Warnings/Precautions
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 (Davenport 2018).
- Shock states: Use with caution in patients with shock and hypoperfusion to muscles.Citrate is partially metabolized by muscles and may accumulate with hypoperfusion leading to toxicity. Considered contraindicated in patients with cardiogenic shock and blood lactate concentrations >8 mmol/L (Davenport 2018).
Monitoring Parameters
Check serum electrolytes ~15 minutes and 1 hour after starting continuous renal replacement therapy (CRRT), then at least every 6 hours for CRRT; particularly monitor iCa, sodium, potassium, chloride, magnesium, and bicarbonate to avoid metabolic aberrancies; 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 (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).
