Introduction
Trauma is a leading cause of death in the US, and uncontrolled hemorrhage is often the primary cause of mortality. The lethal triad of trauma includes coagulopathy, hypothermia, and acidosis, with calcium being heavily involved in the coagulation cascade.
Calcium plays a vital role in coagulation and platelet function, being required by clotting factors II, VII, IX, and X, proteins C and S, and plays a role in stabilizing fibrinogen and platelets in the developing thrombus. Serum calcium is chelated due to the citrate used as a preservative in the Packed Red Blood Cells (PRBC’s), Fresh Frozen Plasma (FFP), and other blood products.
While rapidly metabolized in healthy patients, citrate clearance is reduced in hemorrhagic shock and accumulates with rapidly infused blood products commonly used in massive transfusion protocol (MTP). Previous work suggests that 2–15 units of blood are needed to produce a drop in calcium.
Clinical Detail
IV Calcium: Calcium Chloride vs. Calcium Gluconate
| Property | Calcium Chloride | Calcium Gluconate |
|---|---|---|
| Dose | 1–3 grams | 1–3 grams |
| Administration | Infusion of 200 mg/min • IV push in emergent situations • Central line administration preferred | Slow IV push administration over 5–10 minutes • May give through peripheral IV line • 200 mg/min |
| Formulation | 100 mg/mL (10%) contains 13.6 mEq/10 mL | 100 mg/mL (10%) contains 4.65 mEq EC/10 mL |
| Adverse Effects | Arrythmias, bradycardia, cardiac arrest, syncope, tingling, necrosis of tissue (chloride > gluconate) | Arrythmias, bradycardia, cardiac arrest, syncope, tingling, necrosis of tissue (chloride > gluconate) |
| Drug Interactions and Warnings | Extravasation: Calcium is a vesicant, administration into tissue can cause necrosis. Not to be used when patient is in ventricular fibrillation in cardiac resuscitation | Extravasation: Calcium is a vesicant, administration into tissue can cause necrosis. Not to be used when patient is in ventricular fibrillation in cardiac resuscitation |
| Compatibility | Epinephrine, norepinephrine, sodium bicarbonate, and blood products | Epinephrine, norepinephrine, sodium bicarbonate, and blood products |
| Comments | Calcium Chloride has 3x higher elemental calcium than calcium gluconate | Calcium Chloride has 3x higher elemental calcium than calcium gluconate |
Mechanism: How Trauma & Transfusion Drive Hypocalcemia
| Factor | Effect on Calcium & Coagulation |
|---|---|
| Hypothermia | Causes decrease in liver metabolism of citrate. Citrate not metabolized in the liver binds to Ca2+, leading to less Ca2+ available in the blood. |
| Acidosis | Low Ca2+ levels associated with low pH. Lower pH prolongs clot formation. |
| Coagulopathy | Ca2+ in the plasma is a necessary co-factor for clotting. |
| Hypocalcemia | Ca2+ levels drop due to blood loss. Transfusion further exacerbates. |
Evidence
| Author, Year | Design / Sample Size | Outcome |
|---|---|---|
| Vasudeva, 2020 | Retrospective review N=226 | • 50% of patients recorded ionized hypocalcemia on presentation prior to any blood product transfusion • Ionized hypocalcemia was associated with coagulopathy in patients with shock index ≥1 • Admission ionized hypocalcemia was associated with death at hospital discharge (25% of hypocalcemic patients vs 15% of normocalcemic patients) |
| Kyle, 2017 | Retrospective review N=297 | • The incidence of hypocalcemia in the non-treatment group was 70.0% vs 28.3% in the treatment group • In the non-treatment group, 26.6% had normal calcium levels vs 41.7% in those who received calcium • After only 1 unit of blood, calcium levels drop below the lower limit of normal • A dose response of calcium level to blood products was observed, with a significant decrease in calcium levels as the volume of blood products increased |
| Giancarelli, 2016 | Retrospective review N=156 | • 97% experienced hypocalcemia and 71% had severe hypocalcemia • Mortality was higher in the severe hypocalcemia group (49% vs 24%) • Patients in the iCa < 0.90 group received more blood products (34 vs 22 units) |
| Webster, 2016 | Retrospective cohort analysis N=55 | • 55% of patients were hypocalcemic on ED arrival • 89% of patients were hypocalcemic after receiving any amount of blood product |
| Magnotti, 2011 | Prospective cohort N=591 | • Low iCa levels at admission were associated with increased mortality as well as an increased need for both multiple transfusions and massive transfusion • Multivariable logistic regression analysis identified low iCa levels as an independent predictor of multiple transfusions |
| Vivien, 2005 | Prospective cohort N=212 | • A normal iCa concentration was observed in 56 (26%) patients, mild ionized hypocalcemia in 135 (64%) patients, and severe iCa in 21 (10%) patients • There was a significant correlation between iCa concentration and the amount of infused colloid |
iCa = ionized calcium.
Conclusions
ionized calcium levels during resuscitation
References
- Cause decrease in liver metabolism of citrate
- Citrate not metablolized in the liver binds to Ca2+ leading to less Ca2+ available in
- Low Ca2+ levels associated with low pH
- Lower pH prolongs clot formation
- Ca2+ in the plasma is necesarry co-factor for clotting
- Ca2+ levels drop due to blood loss
- Transfusion further exacerbates
Calcium chloride. Micromedex [Electronic version].Greenwood Village, CO: Truven Health
Analytics. Retrieved June 17, 2020, from http://www.micromedexsolutions.com/
Vasudeva M, et al. Hypocalcaemia and traumatic coagulopathy: an observational analysis.
Vox Sang. 2020;115(2):189-195. doi:10.1111/vox.12875Giancarelli A, et al. Hypocalcemia in
trauma patients receiving massive transfusion. J Surg Res. 2016 May; 202(1):182-187.
Kyle T, et al. Emerg Med J. 2018;35(3):176-179. doi:10.1136/emermed-2017-206717
Giancarelli A, et al. J Surg Res. 2016;202(1):182-187. doi:10.1016/j.jss.2015.12.036
Webster S, et al. Emerg Med J. 2016;33(8):569-572. doi:10.1136/emermed-2015-205096
Magnotti LJ, et al. J Trauma. 2011;70(2):391-397.
Vivien B, et al. Crit Care Med. 2005;33(9):1946-1952. doi:10.1097/01.ccm.0000171840.01892.36
Ditzel RM, et al. J Trauma Acute Care Surg. 2020;88(3):434-43
the blood
Hypothermia
Acidosis
Coagulopathy
Hypocalcemia
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