Empiric Calcium in Massive Transfusion

Study Overview
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Brief Summary
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Calcium helps blood to clot and thereby stop bleeding. Trauma patients who experience large volume blood loss often require blood transfusions and bleeding is the most common cause of death. The purpose of this study is to see if giving intravenous calcium immediately to patients who require large volume blood transfusion will decrease transfusion requirements, vasopressor use and mortality in bleeding trauma patients.

Detailed Description
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Advancements in the area of transfusion and blood product administration have occurred with the use of viscoelastic assays and whole blood. However, as we resuscitate trauma patients with blood products, hypocalcemia is an inadvertent side-effect. Citrate within stored blood binds calcium, causing patients to have hypocalcemia. In addition, outside of transfusion related hypocalcemia there is an independent trauma/inflammation related mechanism for hypocalcemia in the trauma patient. Furthermore, Calcium is a critical component of the coagulation cascade, and therefore a highly important component of hemostatic resuscitation. Hall et al found that patients receiving 13 or more units of PRBCs had a much higher prevalence of severe hypocalcemia and at least one ionized calcium <1.0mmol/L. Kronstedt el al reported an association between hypocalcemia and mortality in trauma patients receiving massive transfusion. Despite evidence that hypocalcemia occurs with transfusion, and evidence that hypocalcemia in patients with hemorrhagic shock may be associated with increased mortality, there are no randomized controlled trials evaluating the administration of calcium in trauma resuscitation. Currently, the Joint Trauma System revised guidelines for damage control resuscitation from 2019 recommend administering 1g of calcium after the first unit of blood transfusion, and an additional 1g after no more than 4 units of blood administration. However, these recommendations are based on small cohort studies or retrospective studies. The purpose of this study is to evaluate the efficacy of early empiric intravenous calcium administration on transfusion requirements, vasopressor use and mortality in hemorrhaging trauma patients with initiation of a massive transfusion. All trauma patients in which massive transfusion is initiated within 6 hours of arrival will be enrolled. Two study arms will be created, one will receive 2g IV calcium with the initial transfusion and the other will only receive calcium supplementation based on routine ionized calcium levels and/or physician discretion. All critical trauma activations will get a baseline ionized calcium as part of their initial labs.

Official Title
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Empiric Calcium Versus Lab Based Treatment in Massive Transfusion Trauma Patients: A Feasibility Randomized Controlled Trial

Conditions
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Hemorrhage, Trauma, Hypocalcemia, Shock, Hemorrhagic

Intervention / Treatment
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* Drug: Calcium Gluconate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Trauma patients receiving massive transfusion protocol Exclusion Criteria: Pregnancy Prisoners Known history of hypercalcemia Active hyperparathyroidism Hemophilia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Empiric calcium administration<br>Patients in this arm will receive 2g IV calcium with the initial transfusion | Drug: Calcium Gluconate<br>* There will be 2 study arms, one will receive 2g IV calcium with the initial transfusion and the other will only receive calcium supplementation based on routine ionized calcium levels and/or physician discretion.<br>* Other names: Calcium;|
| No Intervention: No empiric calcium administration<br>Patients in this arm will only receive calcium supplementation based on routine ionized calcium levels and/or physician discretion | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transfusion requirements | Number of packed red blood cells, whole blood, fresh frozen plasma, platelets and cryo units given | During first 24 hours of resuscitation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality | 30-day mortality or until discharge (whichever is longer) | 30-day mortality | 
| Vasopressor use | Amount of vasopressor used within the first 24 hours measured in levophed equivalents | During first 24 hours of resuscitation |