What happens to citrate from citrate-containing blood products once administered into the body?

Citrate Metabolism from Blood Products

Citrate from blood products enters the systemic circulation and is metabolized primarily in the liver, as well as in the kidneys and skeletal muscle, where it is converted into bicarbonate and energy through the Krebs cycle. 1

Primary Metabolic Pathway

• Citrate is metabolized predominantly in the liver, with additional metabolism occurring in the kidneys and skeletal muscle 1
• Citrate functions as an intermediate metabolite of the Krebs cycle (tricarboxylic acid cycle), allowing it to enter cells without requiring insulin for cellular uptake 1
• Each mmol of citrate metabolized yields 0.59 kcal of energy and generates 3 mmol of bicarbonate 1
• The energy contribution from citrate can be substantial: approximately 3 kcal per gram of citrate administered 1

Clinical Consequences of Citrate Metabolism

Energy Provision

• During kidney replacement therapy with citrate anticoagulation, patients can receive 100-1300 kcal/day from citrate metabolism alone, depending on the citrate concentration and infusion rates used 1
• With ACD-A citrate solutions, citrate can contribute approximately 218 kcal/day on average 1
• This caloric load must be included in total daily energy calculations to avoid overfeeding 1

Acid-Base Effects

• Citrate metabolism generates bicarbonate, which can lead to metabolic alkalosis, particularly in patients receiving frequent or massive transfusions 2, 3, 4
• The conversion of citrate to bicarbonate increases blood pH and can cause decompensated metabolic alkalosis combined with respiratory acidosis due to elevated carbon dioxide production 2, 4
• In non-massive but frequent transfusions (10-30 mL/kg/day), citrate loads averaging 43.2 mg/kg/day can cause intracellular acidosis with compensatory metabolic alkalosis 2, 4

Calcium Binding and Hypocalcemia

• Citrate binds ionized calcium in the bloodstream, causing hypocalcemia that is typically transient during standard transfusions as citrate undergoes rapid hepatic metabolism 1
• Ionized calcium levels should be maintained above 0.9 mmol/L during massive transfusion, as hypocalcemia impairs both coagulation (fibrin polymerization and platelet function) and cardiovascular function (contractility and vascular resistance) 1, 5, 6
• Calcium chloride at 1 gram per liter of citrated blood products is the preferred replacement agent 5

Impaired Citrate Metabolism: Critical Pitfalls

Hepatic Dysfunction

• In acute hepatic failure, citrate metabolism is severely impaired, with total body clearance reduced by approximately 50% (3.31 vs. 6.34 mL/kg/min) and elimination half-life prolonged (49.7 vs. 32.9 minutes) 7
• Patients with liver dysfunction accumulate citrate (levels reaching 1.73 mmol/L vs. 0.99 mmol/L in healthy subjects) and fail to generate the expected alkalotic response 7
• Citrate-containing blood products should be restricted in acute hepatic failure, with close monitoring of ionized calcium to prevent hazardous hypocalcemia 7

Other Conditions Impairing Metabolism

• Citrate metabolism is dramatically impaired by hypoperfusion states, hypothermia, and hepatic insufficiency 1
• These conditions prevent normal hepatic conversion of citrate to bicarbonate, leading to citrate accumulation and prolonged hypocalcemia 1, 7

Monitoring Recommendations

• Ionized calcium should be monitored at baseline and every 4-6 hours during intermittent transfusions, or every 1-4 hours during continuous massive transfusion 5
• Monitor for electrocardiographic changes suggesting hypocalcemia, particularly QT prolongation and dysrhythmias when ionized calcium falls below 0.8 mmol/L 5, 6
• In patients with metabolic alkalosis receiving frequent transfusions, monitor venous pH, bicarbonate levels, and electrolytes (sodium, potassium, phosphorus, chloride) 2, 4

Electrolyte Disturbances

• Citrate metabolism correlates with decreased serum calcium and phosphorus levels, and altered sodium and chloride balance 2
• Hypomagnesemia can compound hypocalcemia by impairing parathyroid hormone secretion 6
• The combination of metabolic alkalosis, electrolyte imbalance, and intracellular acidosis from citrate metabolism may contribute to increased mortality in patients receiving frequent non-massive transfusions 2, 4