Polishing One Edge of the Lethal Diamond - a Study on Incidents of Hypocalcemia in Massive Transfusion Protocol and Its Role in Trauma Patient Outcomes

Introduction:

In the United States, Hemorrhage is the most common cause of mortality in trauma patients. The key lifesaving intervention for these patients is to promptly initiate the Massive Transfusion Protocol (MTP). Originally, the factors included in the lethal triad associated with trauma were coagulopathy (INR>1.5), acidosis (PH <7.21), and hypothermia (<35°C). However, hypocalcemia as an additional parameter is recently being studied, making the triad into a lethal diamond. There are approximately 3g of citrate anticoagulant in every unit of Fresh Frozen Plasma (FFPs)/Packed Red Blood Cells(PRBCs). Hepatic clearance is impaired in a shock state, leading to increased citrate in the blood stream, leading to calcium chelation and hypocalcemia. Severe Hypocalcemia is defined as calcium of <0.9 mmol/L, associated with adverse cardiac effects and increased mortality in critically ill patients. MTP has been shown to cause hypocalcemia and worsen prognosis in this patient population. This study aims to determine the incidence of hypocalcemia in MTP and to assess it as an independent risk factor increasing mortality in this population.

Methods:

This is a single center, retrospective, and observational study that investigated 74 patients with severe trauma treated with MTP in an American College of Surgeons verified Level II Trauma Center between 2018-2022. Patient data in our study was collected from documentation in trauma flow sheets from electronic medical records. Adequate calcium replacement was defined as 1gm of calcium chloride/gluconate for every 4 units of blood transfused. Primary outcome was to determine the percentage of patients who developed hypocalcemia with ionized Ca <0.9 mmol/L following initiation of MTP and receiving at least 4 units of blood products, and to assess hypocalcemia as an independent risk factor for mortality. Secondary outcome was to determine if hypocalcemia increases the risk of mortality in patients with one or more factors of the lethal triad.

Result:

The interim data consists of 74 patients. Upon review, severe hypocalcemia was seen in 25% of patients at baseline and 21% of patients after receiving at least 4 units of blood after initiation of MTP. Thirteen patients who presented with normal ionized calcium at baseline developed hypocalcemia after 4 units of transfusion. Mortality among this subgroup was 30.76%, compared to 28.38% across the overall study population. For subgroup analysis among 24 patients with one or more parameters of lethal triad present, hypocalcemia was present in 9 patients. Mortality among this subgroup was 44%. Calcium replacement was done in 60.8% of patients in this study, and among these patients, 13.5% received adequate calcium replacement. We observed a lower mortality than expected due to hypocalcemia as an independent risk factor in this population.

Conclusion:

Hypocalcemia did not appear to independently increase mortality as claimed in previous literatures, which may be limited by a small sample size and lack of classification by injury severity scores. However, when combined with the lethal triad, it was shown to increase mortality in patients receiving MTP. Implementing calcium supplementation as a part of the massive transfusion protocol might improve overall patient outcomes.