What is the recommended approach for citrate anticoagulation in patients undergoing Continuous Renal Replacement Therapy (CRRT)?

Citrate Anticoagulation in CRRT

Regional citrate anticoagulation should be your first-line anticoagulation strategy for CRRT in all patients unless specific contraindications exist, as it significantly reduces bleeding risk compared to heparin while maintaining equivalent circuit survival. 1

Primary Recommendation and Evidence Base

• Use regional citrate anticoagulation as the preferred strategy over heparin or no anticoagulation for all CRRT patients without contraindications (Grade 2B recommendation). 1
• Citrate reduces major bleeding risk by 66% compared to heparin (RR 0.34,95% CI 0.17-0.65) while maintaining similar circuit survival times. 2
• This recommendation applies even to patients without increased bleeding risk, not just high-risk populations. 1

Absolute Contraindications to Citrate

Screen for these contraindications before initiating citrate anticoagulation:

• Severe liver failure with inability to metabolize citrate - this is the primary absolute contraindication. 1
• Shock with muscle hypoperfusion and persistent lactic acidosis due to poor tissue perfusion, as the citric acid cycle is oxygen-dependent. 3
• Baseline severe metabolic abnormalities that would be exacerbated by citrate. 1

Alternative Anticoagulation When Citrate is Contraindicated

If citrate cannot be used, follow this hierarchy:

• For patients with increased bleeding risk: Run CRRT without anticoagulation rather than using heparin. 4, 5
• For patients without increased bleeding risk: Use unfractionated heparin or low-molecular-weight heparin as second-line agents. 1
• For heparin-induced thrombocytopenia (HIT): Immediately stop all heparin products and use direct thrombin inhibitors (argatroban preferred if no severe liver failure) or Factor Xa inhibitors (Grade 1A recommendation). 1, 5

Practical Implementation Protocol

Citrate Dosing and Circuit Management

• Infuse citrate (typically as acid citrate dextrose solution) at 1.6-3.7% of blood flow rate to maintain circuit ionized calcium <0.5 mmol/l. 6
• Use calcium-free replacement fluid with reduced alkali (NaHCO₃ 20 mEq/L) in pre-filter mode. 6
• Infuse calcium chloride (0.8%) separately through a central line at 25-50% of citrate infusion rate to maintain systemic ionized calcium between 1.0-1.3 mmol/L. 6
• Expected citrate clearance is 31-38 ml/min per 1.73 m², similar to urea clearance. 6

Mandatory Monitoring Requirements

Monitor the following parameters every 4-6 hours: 1

• Systemic ionized calcium - watch for both hypocalcemia and hypercalcemia (particularly in liver dysfunction patients). 4, 7
• Acid-base status - metabolic alkalosis occurs in >50% of patients, typically within first 72 hours. 7
• Serum sodium - to prevent hypernatremia. 4
• Electrolytes - particularly magnesium (lost as magnesium-citrate complexes), phosphate, and potassium. 4

Prevention of Metabolic Complications

• Implement a strict written protocol with mandatory comprehensive staff education - this is critical to prevent prescription errors. 4, 1
• Use commercial CRRT solutions enriched with phosphate, potassium, and magnesium when available. 1
• For metabolic alkalosis (develops in >50% of patients): Increase dialysate flow rate to reverse alkalosis. 7
• Use dialysate with appropriate electrolyte composition, particularly increased magnesium concentration. 4

Special Populations and Considerations

Patients with Liver Dysfunction

• Citrate can be used in patients with significant liver disease provided monitoring is intensified and dose is carefully adjusted. 3
• Patients with impaired liver function are at particular risk for hypercalcemia due to reduced citrate metabolism. 7
• Monitor systemic ionized calcium levels closely for signs of citrate accumulation. 4

Thrombocytopenic Patients

• Regional citrate anticoagulation is recommended for thrombocytopenic patients without citrate contraindications. 4
• Base the decision on overall risk-benefit assessment, not solely on platelet count. 4
• If citrate is contraindicated, run CRRT without anticoagulation rather than using heparin. 4

Clinical Outcomes and Cost-Effectiveness

• Filter life is significantly longer with citrate (80.2 ± 60 hours) versus heparin (30.2 ± 32 hours), translating to significant cost reduction. 7
• Citrate may reduce inflammation through hypocalcemia-induced suppression of intracellular signaling and avoidance of heparin's proinflammatory properties. 3
• Convective clearance (CVVH) alone provides sufficient citrate clearance; diffusive clearance (CVVHDF) is not mandatory. 6

Common Pitfalls to Avoid

• Do not use subclavian vein access - prefer right internal jugular vein due to thrombosis and stenosis risk. 1, 5
• Anticipate metabolic alkalosis within the first 72 hours and adjust dialysate flow accordingly. 7
• Do not assume citrate is contraindicated in all liver disease - only severe liver failure is an absolute contraindication. 3
• Ensure integrated citrate software or strict protocols are in place before implementation to prevent dosing errors. 4