What is the recommended citrate anticoagulation protocol for a critically ill patient with acute kidney injury (AKI) requiring Continuous Renal Replacement Therapy (CRRT)?

Citrate Anticoagulation Protocol for CRRT

Primary Recommendation

Regional citrate anticoagulation (RCA) is the preferred anticoagulation strategy for CRRT in critically ill patients with AKI who lack contraindications to citrate, offering superior filter patency compared to heparin with minimal bleeding risk. 1, 2

Protocol Implementation Requirements

Before initiating RCA, establish a strict institutional protocol with comprehensive staff education to prevent prescription errors and metabolic complications 1, 2. The protocol must specify:

• Citrate infusion rates adjusted to body weight and dialysate flow 3
• Calcium replacement infusion rates to maintain systemic ionized calcium 2, 3
• Dialysate and replacement fluid composition (bicarbonate-based preferred) 2
• Metabolic monitoring intensity and frequency 1, 2

Weight-Based Dosing Algorithm

Adjust citrate and dialysate flows according to patient body weight 3:

• <60 kg body weight: Lower citrate and dialysate flows 3
• 60-90 kg body weight: Standard flows (approximately 2 L/hr dialysate for average body size) 3
• >90 kg body weight: Higher citrate and dialysate flows 3

Blood flow, citrate flow, and calcium flow should be proportionally adjusted to match the dialysate flow used 3.

Essential Monitoring Parameters

Calcium Monitoring

• Post-filter ionized calcium: Target <0.5 mmol/L to ensure adequate anticoagulation 3, 4
• Systemic ionized calcium: Maintain at physiologic levels (approximately 1.1 mmol/L) 2, 4
• Total calcium to ionized calcium ratio: Monitor to detect citrate accumulation 1, 2

Acid-Base and Electrolyte Monitoring

• Systemic acid-base balance: Regular assessment, particularly in high-risk patients 2
• Serum sodium: Frequent monitoring to prevent hypernatremia 1, 2
• Magnesium levels: Critical monitoring as magnesium-citrate complexes are lost in effluent 2
• Potassium and phosphate: Monitor for common CRRT-related depletion 2

Contraindications and High-Risk Situations

Relative (Not Absolute) Contraindications

Severe liver failure and shock with muscle hypoperfusion are listed as major contraindications by KDIGO, but multiple studies demonstrate these are relative rather than absolute contraindications 1, 2:

• In liver failure, track citrate accumulation via systemic ionized calcium and total calcium/ionized calcium ratio 1, 2
• In septic shock, RCA has been safely used in multiple randomized trials 1, 2
• Consider no anticoagulation or intermittent modalities (e.g., SLED) if severe liver failure with coagulopathy exists 1

Signs of Citrate Accumulation

Citrate toxicity occurs in approximately 5% of patients and is indicated by 3:

• Total calcium >3 mmol/L 3
• Requirement for high calcium substitution rates 3
• Widening total calcium to ionized calcium ratio 1, 2

Fluid Composition Strategies

Use dialysate and replacement fluids enriched with electrolytes rather than relying on intravenous supplementation 2:

• Magnesium: Increased concentration essential due to magnesium-citrate complex losses 2
• Potassium and phosphate: Include in dialysis solutions to prevent depletion 2
• Bicarbonate-based solutions: Preferred over lactate-based, especially in shock or liver failure 2

Troubleshooting Metabolic Derangements

When metabolic abnormalities occur during RCA 3:

• Metabolic alkalosis or acidosis: Modify dialysate flow rate first 3
• Persistent acid-base disturbance: Alternatively adjust blood flow rate 3
• Hypernatremia: Reduce citrate infusion or modify dialysate sodium concentration 1, 2

Expected Filter Performance

With proper RCA protocol 3:

• Median filter run time: 61.5 hours (interquartile range 34.5-81.1 hours) 3
• Only 5% of filters require premature change due to clotting 3
• Routine filter changes at 72 hours 3

Special Populations

Patients with Increased Bleeding Risk

RCA is preferred over no anticoagulation in patients with bleeding risk who lack citrate contraindications 1. Regional heparinization should be avoided in bleeding-risk patients 1.

Heparin-Induced Thrombocytopenia (HIT)

All heparin must be stopped immediately 1. Use direct thrombin inhibitors (argatroban preferred if no severe liver failure) or Factor Xa inhibitors (danaparoid, fondaparinux) 1.

U.S.-Specific Limitation

In the United States, citrate is not FDA-approved for CRRT anticoagulation, and commercially available solutions are hypertonic blood banking products, limiting universal recommendation until standardized protocols and appropriate citrate solutions are developed and approved 2.