Regional anticoagulation for CRRT 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: Use is generally considered 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 ACD-A solution: Approximate usual initial infusion rate: ~1.5 to 1.8 times the blood flow rate; for example, if blood flow rate is 100 to 200 mL/minute, start ACD-A infusion at 150 to 360 mL/hour (Ref). Optimal ACD-A regimens have not been identified; refer to institutional protocols as variations exist. Adjustment of ACD-A 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 ionized calcium between 1 to 1.4 mg/dL (0.25 to 0.35 mmol/L) (Ref).
Serum calcium: Monitor systemic ionized calcium peripherally (drawn directly from the patient), and maintain between 3.6 to 4.8 mg/dL (0.9 to 1.2 mmol/L) (Ref).
Not applicable. This product is used in the extracorporeal blood processing with Autologous PRP systems in production of platelet rich plasma (PRP); it is not for direct intravenous infusion.
Direct intravenous infusion
Disease-related concerns:
• Hepatic impairment: When used for regional anticoagulation of the CRRT circuit: 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; Szamosfalvi 2021).
• Shock states: When used for regional anticoagulation of the CRRT circuit: 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).
Other warnings/precautions:
• Appropriate use: Not intended for direct intravenous infusion into patients; when used in extracorporeal blood processing for the production of platelet rich plasma, must be used with the Autologous PRP system. Discard if closure system's biological barrier is not intact.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Solution, In Vitro:
ACD Formula A: Citric acid 0.73 g, dextrose monohydrate 2.45 g, and sodium citrate dihydrate 2.2 g per 100 mL (500 mL [DSC], 1000 mL)
ACD-A noClot-50: Citric acid anhydrous 0.073 g, dextrose monohydrate 0.245 g, and sodium citrate dihydrate 0.22 g per 10 mL (50 mL)
Generic: Citric acid monohydrate 0.8 g, dextrose monohydrate 2.45 g, and sodium citrate dihydrate 2.2 g per 100 mL (750 mL [DSC])
Yes
Solution (ACD-A noClot-50 In Vitro)
0.73-2.45-2.2 g/100 mL (per mL): $0.75
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, In Vitro:
Generic: Citric acid 0.73 g, dextrose monohydrate 2.45 g, and sodium citrate dihydrate 2.2 g per 100 mL (500 mL, 1000 mL)
Anticoagulant used in the extracorporeal blood processing with Autologous PRP systems in production of platelet rich plasma
Regional anticoagulation for continuous renal replacement therapy circuit
Anticoagulant citrate dextrose may be confused with anticoagulant sodium citrate
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 ionized calcium, 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/ionized calcium) (calcium ratio may indicate citrate toxicity if >2.1); monitoring postfilter ionized calcium 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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