Best Practice for Calcium Administration in Massive Transfusion Protocols
Calcium chloride is the preferred agent for calcium replacement during massive transfusion protocols, administered at 1 gram per liter of citrated blood products transfused to maintain ionized calcium levels above 0.9 mmol/L. 1, 2
Monitoring Recommendations
- Monitor ionized calcium levels at baseline and every 4-6 hours during intermittent transfusions, or every 1-4 hours during continuous massive transfusion 2, 3
- Normal ionized calcium range is 1.1-1.3 mmol/L and is pH-dependent (a 0.1 unit increase in pH decreases ionized calcium by approximately 0.05 mmol/L) 1, 2
- Low ionized calcium at admission is associated with increased mortality, need for massive transfusion, platelet dysfunction, decreased clot strength, and coagulopathy 1, 4
- Laboratory coagulation tests may not accurately reflect the impact of hypocalcemia on coagulation, as blood samples are citrated and then recalcified before analysis 1
Calcium Replacement Protocol
Indications for Treatment
- Maintain ionized calcium levels >0.9 mmol/L to support cardiovascular function and coagulation 1, 2
- Promptly correct hypocalcemia when ionized calcium levels fall below 0.9 mmol/L or when total corrected calcium levels are ≤7.5 mg/dL 1, 2
- Cardiac dysrhythmias are particularly concerning when ionized calcium is <0.8 mmol/L 1, 2
Calcium Chloride Administration
- Calcium chloride is the preferred agent for treatment of hypocalcemia during massive transfusion 1, 2
- Administer 1 gram of calcium chloride per liter of citrated blood products transfused, in divided doses 5
- 10 mL of 10% calcium chloride solution contains 270 mg of elemental calcium 1, 6
- Administer via slow intravenous injection (not to exceed 1 mL/min), preferably in a central or deep vein 6
- Calcium chloride is more effective than calcium gluconate in patients with liver dysfunction due to faster release of ionized calcium 1, 2
Alternative: Calcium Gluconate Administration
- If calcium chloride is unavailable, calcium gluconate can be used 2
- 10 mL of 10% calcium gluconate contains only 90 mg of elemental calcium (one-third the elemental calcium of calcium chloride) 1, 3
- Requires three times the volume to deliver equivalent elemental calcium compared to calcium chloride 1, 2
Implementation of Calcium Replacement Protocol
- A standardized calcium replacement protocol significantly reduces the incidence of hypocalcemia (63% vs 95.2%) during massive transfusion 7
- Time to first calcium dose is significantly shorter with a protocol in place (median 5.5 minutes vs 43 minutes) 7
- Empiric calcium replacement of 1 gram calcium chloride per liter of blood transfused has been shown to maintain ionized calcium levels even during extreme massive transfusion 5
Special Considerations
- Hypocalcemia in trauma patients is often related to citrate toxicity from blood product transfusions (especially FFP and platelets) 1, 2
- Hypocalcemia is exacerbated by hypoperfusion, hypothermia, or hepatic insufficiency, which impair citrate metabolism 1, 2
- Colloid infusions (but not crystalloids) can contribute to hypocalcemia 1
- Calcium gluconate is not physically compatible with fluids containing phosphate or bicarbonate; precipitation may result if mixed 3
- No studies have definitively demonstrated that prevention or treatment of hypocalcemia reduces mortality in patients with critical bleeding requiring massive transfusion, but the association with mortality is clear 1, 4
Common Pitfalls
- Waiting for laboratory confirmation of hypocalcemia before initiating calcium replacement during massive transfusion 7
- Using calcium gluconate instead of calcium chloride in patients with liver dysfunction 1, 2
- Inadequate monitoring of ionized calcium levels during ongoing massive transfusion 4
- Failure to recognize that a ratio of 0.9 mmol of administered calcium per citrated blood product may lead to hypercalcemia 8
- Underestimating the impact of hypocalcemia on coagulation and cardiovascular function 1, 4