What is the treatment for citrate toxicity?

Treatment of Citrate Toxicity

The treatment for citrate toxicity requires immediate administration of calcium, preferably calcium chloride, to restore ionized calcium levels when hypocalcemia is detected during continuous renal replacement therapy or other procedures using citrate anticoagulation. 1

Understanding Citrate Toxicity

Citrate toxicity occurs primarily in the following contexts:

• During continuous renal replacement therapy (CRRT) with regional citrate anticoagulation
• During plasma exchange or apheresis procedures
• During massive transfusion of citrate-containing blood products (especially FFP and platelets)

Pathophysiology

• Citrate binds to ionized calcium, causing hypocalcemia
• Normal citrate metabolism occurs in the liver via the citric acid cycle (Krebs cycle)
• Citrate accumulation is more likely in patients with:
  • Liver failure or impaired hepatic function 2
  • Shock with muscle hypoperfusion 1
  • Certain medications that affect calcium metabolism

Diagnosis of Citrate Toxicity

Key diagnostic findings include:

1. Decreased ionized calcium (< 0.9 mmol/L or < 3.6 mg/dL) 3
2. Normal or elevated total calcium
3. Elevated total calcium to ionized calcium ratio (> 2.5) 4
4. Clinical signs of hypocalcemia:
   • Perioral and peripheral paresthesias
   • Tetany
   • QT interval prolongation
   • Hypotension
   • Cardiac arrhythmias

Treatment Algorithm

Immediate Management

1. For severe symptomatic hypocalcemia:

   • Administer calcium chloride 1-2 mg elemental calcium per kg body weight per hour IV 5
   • For rapid correction in critical situations, give 10 mL of 10% calcium chloride (or 30 mL of 10% calcium gluconate) IV over 5-10 minutes 1
   • Monitor ECG during rapid administration

2. Adjust citrate infusion:

   • Reduce or temporarily stop citrate infusion in CRRT 4
   • Consider alternative anticoagulation methods if citrate toxicity persists

3. Monitor calcium levels:

   • Check ionized calcium every 1-2 hours until stabilized
   • Target ionized calcium level > 0.9 mmol/L (> 3.6 mg/dL) 3

Ongoing Management

1. Continue calcium replacement:

   • Adjust calcium infusion rate based on ionized calcium levels
   • Higher rates may be needed in patients with liver dysfunction (up to 140 mL/h of 10 mEq/dL CaCl₂ has been reported) 4

2. Monitor for metabolic complications:

   • Check acid-base status regularly
   • Monitor total calcium to ionized calcium ratio (ratio >2.5 suggests citrate accumulation) 4
   • Monitor magnesium levels as hypomagnesemia can worsen hypocalcemia 5

3. Consider alternative strategies:

   • For patients with severe liver dysfunction, consider non-citrate based anticoagulation
   • If citrate must be continued, use lower citrate doses with increased calcium supplementation 4

Special Considerations

Liver Dysfunction

• Patients with acute liver failure have approximately 50% reduced citrate clearance 2, 3
• Total body clearance of citrate is significantly reduced (3.31 ± 0.03 ml/kg/min vs 6.34 ± 0.16 ml/kg/min in healthy controls) 2
• Higher calcium replacement requirements should be anticipated
• Monitor the total:ionized calcium ratio closely (>2.5 suggests citrate accumulation) 4

Medications

• Screen for medications that may predispose to hypocalcemia (e.g., loop diuretics like bumetanide) 6
• Consider checking baseline calcium levels in high-risk patients before procedures using citrate

Prevention of Citrate Toxicity

1. Risk assessment:

   • Identify patients with liver dysfunction or shock
   • Screen for medications affecting calcium metabolism
   • Consider baseline calcium measurement in high-risk patients

2. Protocol-based management:

   • Use strict protocols for citrate administration during CRRT 1
   • Regular monitoring of ionized calcium, total calcium, and acid-base status
   • Maintain ionized calcium >0.9 mmol/L 3

3. Alternative approaches for high-risk patients:

   • Consider CRRT without anticoagulation in patients at high bleeding risk 1
   • Consider alternative anticoagulation methods in patients with severe liver dysfunction