Association Between Ionized Calcium Concentrations During Hemostatic Transfusion and Calcium Treatment With Mortality in Major Trauma

Abstract

BACKGROUND: Transfusion of citrated blood products may worsen resuscitation-induced hypocalcemia and trauma outcomes, suggesting the need for protocolized early calcium replacement in major trauma. However, the dynamics of ionized calcium during hemostatic resuscitation of severe injury are not well studied. We determined the frequency of hypocalcemia and quantified the association between the first measured ionized calcium concentration [iCa] and calcium administration early during hemostatic resuscitation and in-hospital mortality. METHODS: We performed a retrospective cohort study of all admissions to our regional level 1 trauma center who (1) were ≥15 years old; (2) presented from scene of injury; (3) were admitted between October 2016 and September 2018; and (4) had a Massive Transfusion Protocol activation. They also (1) received blood products during transport or during the first 3 hours of in-hospital care (1st3h) of trauma center care and (2) had at least one [iCa] recorded in that time. Demographic, injury severity, admission shock and laboratory data, blood product use and timing, and in-hospital mortality were extracted from Trauma Registry and Transfusion Service databases and electronic medical records. Citrate load was calculated on a unit-by-unit basis and used to calculate an administered calcium/citrate molar ratio. Univariate and multivariable logistic regression analyses for the binary outcome of in-hospital death were performed. RESULTS: A total of 11,474 trauma patients were admitted to the emergency department over the study period, of whom 346 (3%; average age: 44 ± 18 years; 75% men) met all study criteria. In total, 288 (83.2%) had hypocalcemia at first [iCa] determination; 296 (85.6%) had hypocalcemia in the last determination in the 1st3h; and 177 (51.2%) received at least 1 calcium replacement dose during that time. Crude risk factors for in-hospital death included age, injury severity score (ISS), new ISS (NISS), Abbreviated Injury Scale (AIS) head, admission systolic blood pressure (SBP), pH, and lactate; all P < .001. Higher in-hospital mortality was significantly associated with older age, higher NISS, AIS head, and admission lactate, and lower admission SBP and pH. There was no relationship between mortality and first [iCa] or calcium dose corrected for citrate load. CONCLUSIONS: In our study, though most patients had hypocalcemia during the 1st3h of trauma center care, neither first [iCa] nor administered calcium dose corrected for citrate load were significantly associated with in-patient mortality. Clinically, hypocalcemia during early hemostatic resuscitation after severe injury is important, but specific treatment protocols must await better understanding of calcium physiology in acute injury.

Hypocalcemia as a predictor of mortality and transfusion. A scoping review of hypocalcemia in trauma and hemostatic resuscitation

“…Mortality was higher in the iCa <0.90 mmol/L group -49% death rate versus 24% in the iCa ≥0.90 group (p = .007). In addition, patients in the iCa <0.90 mmol/L group received more blood products (34 [23-58] vs. 22 [18][19][20][21][22][23][24][25][26][27][28][29][30] units, p < .001) and calcium chloride (4 [2][3][4][5][6][7] vs. 3 [1][2][3][4] g, p = .002), possibly showing a bias by indication in this study. There was no difference in the duration (hours) of the MTP or final iCa levels.…”

The Incidence, Degree, and Timing of Hypocalcemia From Massive Transfusion: A Retrospective Review

“…Giancarelli et al only looked at ionized calcium at one moment in time whereas we looked over a period to review a trajectory and assess for potential timing of intervention. Several recent studies have measured the incidence of hypocalcemia during massive transfusion and found similarly high incidences [7,[9][10][11].…”

“…Clinical signs of hypocalcemia include heart failure, prolonged QT interval, sinus tachycardia, paresthesia, muscle spasms, cramps, tetany, circumoral numbness, and seizures [8]. Given the integral role that calcium plays in coagulation and hemodynamics, it is no surprise that several studies have shown a correlation between hypocalcemia and mortality [7,[9][10][11].…”

Advances in hemorrhage control resuscitation

“…There are no prospective data demonstrating that calcium replacement improves survival. Indeed, Chanthima et al [43 ▪ ] found no relationship between mortality and first ionized calcium level, or calcium supplementation corrected for citrate load.…”