The Pre-brief
Greater than 60,000 deaths are attributed to hemorrhage in the United States with hemorrhage being a leading cause of preventable death after trauma, accounting for 30% of all trauma deaths. The Lethal Triad, aka the “bloody vicious cycle,” consists of coagulopathy, acidosis, and hypothermia. The presence of this constellation of physiological derangements contributes to ongoing hemorrhagic shock, leading to an increase in mortality. Along with hemorrhagic control, blood products are administered in an effort to reverse hemorrhagic shock and massive transfusion protocols may be activated. Complications of massive transfusion include electrolyte derangements, with hypocalcemia being one of the main clinically significant electrolyte abnormalities. Studies show that over half of trauma patients are hypocalcemic prior to receiving any blood product on arrival to the emergency department. Hypocalcemia contributes to coagulopathy, which may lead to continued blood loss and possibly death.
Pathophysiology:
Calcium plays an extremely important role within the body. The vital functions of calcium are seen in coagulation, platelet adhesion, and contractility of myocardial and smooth muscle cells. Calcium is needed for clotting factors II, VII, IX, and X, as well as protein C and S for activation at the damaged epithelium. Calcium also aids in stabilizing fibrinogen and platelets for thrombus formation. An ionized calcium level below 0.8 – 0.9 mmol/L leads to coagulopathy and impaired cardiovascular function.
Hypocalcemia occurs through blood loss and also through chelation of calcium with citrate. Packed red blood cells (PRBCs) and fresh frozen plasma (FFP) contain approximately 3 g of citrate anticoagulant per unit as a preservative. Normally, an individual with a healthy liver can metabolize this amount of citrate within 5 minutes; however, in instances of reduced liver function due to hypoperfusion and hypothermia, combined with rapidly infused blood products, ionized calcium levels begin to decrease as it is chelated by free-floating citrate.
Some have advocated converting the lethal triad into the lethal diamond, with the four points being comprised of coagulopathy, acidosis, hypothermia, and hypocalcemia.
Management:
Calcium supplementation is necessary when hypocalcemia is evident; however, there is no consensus recommendation on calcium administration during massive transfusion. Elmer et. al. advocate using 2 g of intravenous calcium gluconate for 2 – 4 units of PRBCs infused to prevent the development of severe hypocalcemia while checking an ionized calcium every 1 – 2 hours for large volume infusions. Giancarelli et. al. used 2 g of calcium chloride after 4 units of blood transfused in their retrospective review. Recently, in an updated clinical practice guideline on damage control resuscitation from The Joint Trauma System, a United States Military Protocol, it states that 1 g of calcium (30 ml of 10% calcium gluconate or 10 ml of 10% calcium chloride) should be administered “…to patients in hemorrhagic shock during or immediately after transfusion of the first unit of blood product and with ongoing resuscitation after every 4 units of blood products.” It is important to recognize the difference between calcium chloride and calcium gluconate. Calcium chloride (13.6 mEq calcium) provides 3 times more elemental calcium versus calcium gluconate (4.56 mEq). Also, calcium chloride should be administered through a central line as extravasation may lead to tissue necrosis while calcium gluconate may be given peripherally.
The Debrief
- Pathways dependent on calcium such as platelet function, coagulation, and cardiac contractility are disrupted during hemorrhagic shock and subsequent resuscitation with blood products containing citrate.
- Hypocalcemia is a clinically significant electrolyte disturbance that occurs in trauma patients due to hemorrhage and further exacerbated by resuscitation with blood products.
- Calcium chloride contains 3 times more elemental calcium versus calcium gluconate.
- Once resuscitative efforts with blood products have started for a trauma patient in hemorrhagic shock, calcium supplementation should be considered (calcium gluconate 2 – 3 g or calcium chloride 1 g) when 2 – 4 units of PRBCs have been administered.
- When resuscitating your trauma patient, don’t forget about the calcium.
References
- Cannon J. Hemorrhagic shock. NEJM. 2018; 378: 370 – 379.
- Kaffarani H, Velmahos G. Damage control resuscitation in trauma. Scand J Surg. 2014; 103: 81 – 88.
- Hess J, Brohi K, Dutton R, Hauser C, Holcomb J, et. al. The coagulopathy of trauma: a review of mechanisms. J Trauma. 2008. 65: 748–754.
- Cohen M, Christie S. Coagulopathy of trauma. Crit Care Clin. 2017; 133: 101 – 118.
- Giancarelli A, Birrer K, Alban R, Hobbs B, Liu-DeRyke, X. Hypocalcemia in trauma patients receiving massive transfusion. J Surg Res. 2016; 202: 182 – 187.
- Sihler K, Napolitano L. Complications of massive transfusion. CHEST. 2010; 137(1): 209 – 220.
- Ditzel R, Anderson J, Eisenhart W, et. al. A review of transfusion- and trauma-induced hypocalcemia: Is it time to change the lethal triad to the lethal diamond? J Trauma Acute Care Surg. 2019; 88(3): 434 – 439.
- Elmer J, Wilcox S, Raja A. Massive transfusion in traumatic shock. J Emerg Med. 2013; 44(4): 829 – 838.
- Vasudeva M, Mathew J, Groombridge C, et. al. Hypocalcemia in trauma patients: a systematic review. J Trauma Acute Care Surg. Published online November 13, 2020.
- Cap A, Gurney J, Spinella P, et. al. Damage Control Resuscitation (CPG ID:18). Joint Trauma Service Clinical Practice Guideline. Joint Trauma System, the Department of Defense Center of Excellence for Trauma. 2019.
- Kraft M, Btachie I, Sacks G, Kudsk K. Treatment of electrolyte disorders of adult patients in the intensive care unit. Am J Health-Syst Pharm. 2005; 62:1663 – 82.
Any tips on how to administer the calcium? Lots of times it seems we have 3 lines and 3 units of blood going so no way to administer an IVP or IVPB of CaGluc unless you’ve found that you can y site this into the blood?