What is Citrate (Continuous Renal Replacement Therapy) CRRT?

Citrate Anticoagulation in Continuous Renal Replacement Therapy (CRRT)

Regional citrate anticoagulation (RCA) is an effective anticoagulation method for CRRT that prolongs filter life and reduces bleeding risks compared to heparin, but requires strict protocols and careful monitoring to avoid metabolic complications. 1

Mechanism of Action

• Citrate functions as an anticoagulant by chelating calcium ions in the extracorporeal circuit
• By lowering ionized calcium (iCa) concentrations in the filter to <0.5 mmol/L, citrate inhibits the coagulation cascade 2
• The citrate-calcium complexes are partially removed by the filter and partially returned to the patient where they are metabolized primarily by the liver

Advantages of Citrate CRRT

• Longer filter lifespan compared to heparin or no anticoagulation (56 hours vs. 36 hours vs. 22 hours) 1
• Reduced bleeding complications compared to heparin anticoagulation 1
• Lower ICU mortality rates compared to heparin or no anticoagulation 1
• No systemic anticoagulation effect, making it suitable for patients at high risk of bleeding 3

Protocol Implementation

A strict protocol must be established before implementing citrate CRRT, including:

1. Citrate administration: Typically delivered as 2-4% trisodium citrate solution via the prefilter port 4
2. Calcium replacement: Usually administered as calcium gluconate via a central line to maintain systemic ionized calcium levels 4
3. Monitoring parameters:
   • Postfilter ionized calcium (target: <0.5 mmol/L)
   • Systemic ionized calcium (target: ~1.1 mmol/L)
   • Acid-base status
   • Total calcium to ionized calcium ratio (to detect citrate accumulation)

Potential Complications

1. Metabolic alkalosis: More common with citrate (32.5%) than with heparin (16.2%) 1
2. Citrate accumulation: Particularly in patients with impaired citrate metabolism
3. Electrolyte disturbances: Hypernatremia, hypocalcemia
4. Measurement inaccuracies: Postfilter iCa measurements can be unreliable in the low range 2

Special Considerations

Liver Dysfunction

• Traditionally considered a contraindication, but evidence suggests RCA can be safely used with careful monitoring 3, 5
• Monitor for citrate accumulation by following:
  • Total calcium to ionized calcium ratio
  • Metabolic acidosis with increasing anion gap
  • Worsening hypocalcemia despite calcium supplementation 3

Shock States

• The Canadian Society of Nephrology does not consider shock an absolute contraindication to citrate CRRT 3
• Several randomized controlled trials have demonstrated safety in patients with severe septic shock 3

Monitoring Recommendations

• Postfilter iCa: Target <0.5 mmol/L, monitor frequently to adjust citrate flow 2
• Systemic iCa: Target ~1.1 mmol/L, adjust calcium replacement accordingly 4
• Acid-base status: Regular monitoring of pH and bicarbonate
• Total calcium to ionized calcium ratio: Increasing ratio suggests citrate accumulation
• Filter pressures: To detect early clotting

Regulatory Status

In the United States, citrate is not FDA-approved specifically as an anticoagulant for CRRT 3. The commercially available citrate solutions are approved for use with automated apheresis devices 6, which creates challenges:

• Available solutions are hypertonic (4% w/v)
• Increased risk of metabolic complications
• Need for standardized protocols 3

Simplified Approaches

Recent innovations include simplified citrate protocols:

• Inclusion of citrate and calcium in all CRRT solutions to eliminate the need for separate calcium replacement 7
• Use of 2% trisodium citrate instead of 4% to reduce metabolic complications 4

Conclusion

Regional citrate anticoagulation represents an effective approach for CRRT, particularly in patients at high risk of bleeding. While implementation requires careful protocol development and monitoring, the benefits of extended filter life and reduced bleeding complications make it a valuable option in the critical care setting.