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

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. 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. 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. 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.

Chanthima P ，Yuwapattanawong K ，Thamjamrassri T ，Nathwani R ，Stansbury LG ，Vavilala MS ，Arbabi S ，Hess JR ... -  《-》

Impact of hypocalcemia on mortality in pediatric trauma patients who require transfusion.

Admission hypocalcemia has been associated with poor outcomes in injured adults. The impact of hypocalcemia on mortality has not been widely studied in pediatric trauma. A pediatric trauma center database was queried retrospectively (2013-2022) for children younger than 18 years who received blood transfusion within 24 hours of injury and had ionized calcium (iCal) level on admission. Children who received massive transfusion (>40 mL/kg) prior to hospital arrival or calcium prior to laboratory testing were excluded. Hypocalcemia was defined by the laboratory lower limit (iCal <1.00). Main outcomes were in-hospital mortality and 24-hour blood product requirements. Logistic regression analysis was performed to adjust for Injury Severity Score (ISS), admission shock index, Glasgow Coma Scale (GCS) score, and weight-adjusted total transfusion volume. In total, 331 children with median (IQR) age of 7 years (2-3 years) and median (IQR) ISS 25 (14-33) were included, 32 (10%) of whom were hypocalcemic on arrival to the hospital. The hypocalcemic cohort had higher ISS (median (IQR) 30(24-36) vs. 22 (13-30)) and lower admission GCS score (median (IQR) 3 (3-12) vs. 8 (3-15)). Age, sex, race, and mechanism were not significantly different between groups. On univariate analysis, hypocalcemia was associated with increased in-hospital (56% vs. 18%; p < 0.001) and 24-hour (28% vs. 5%; p < 0.001) mortality. Children who were hypocalcemic received a median (IQR) of 22 mL/kg (7-38) more in total weight-adjusted 24-hour blood product transfusion following admission compared to the normocalcemic cohort ( p = 0.005). After adjusting for ISS, shock index, GCS score, and total transfusion volume, hypocalcemia remained independently associated with increased 24-hour (odds ratio, 4.93; 95% confidence interval, 1.77-13.77; p = 0.002) and in-hospital mortality (odds ratio, 3.41; 95% confidence interval, 1.22-9.51; p = 0.019). Hypocalcemia is independently associated with mortality and receipt of greater weight-adjusted volumes of blood product transfusion after injury in children. The benefit of timely calcium administration in pediatric trauma needs further exploration. Prognostic and Epidemiological; Level III.

Abou Khalil E ，Feeney E ，Morgan KM ，Spinella PC ，Gaines BA ，Leeper CM ... -  《-》

Ultramassive Transfusion for Trauma in the Age of Hemostatic Resuscitation: A Retrospective Single-Center Cohort From a Large US Level-1 Trauma Center, 2011-2021.

Uncontrolled bleeding is a leading cause of death in trauma. In the last 40 years, ultramassive transfusion (UMT; ≥20 units of red blood cells [RBCs]/24 hours) for trauma has been associated with 50% to 80% mortality; the question remains as to whether the increasing number of units transfused in urgent resuscitation is a marker of futility. We asked whether the frequency and outcomes of UMT have changed in the era of hemostatic resuscitation. We performed a retrospective cohort study of all UMTs in the first 24 hours of care over an 11-year period at a major US level-1 adult and pediatric trauma center. UMT patients were identified, and a dataset was built by linking blood bank and trauma registry data, then reviewing individual electronic health records. Success in achieving hemostatic proportions of blood products was estimated as (units of plasma + apheresis-platelets-in-plasma + cryoprecipitate-pools + whole blood]/[all units given] ≥0.5. Demographics, injury type (blunt or penetrating), severity (Injury Severity Score [ISS]), severity pattern (Abbreviated Injury Scale score for head [AIS-Head] ≥4), admitting laboratory, transfusion, selected emergency department interventions, and discharge status were assessed using χ2 tests of categorical association, the Student t-test of means, and multivariable logistic regression. P <.05 was considered significant. Among 66,734 trauma admissions from April 6, 2011 to December 31, 2021, we identified 6288 (9.4%) who received any blood products in the first 24 hours, 159 of whom received UMT (0.23%; 154 aged 18-90 + 5 aged 9-17), 81% in hemostatic proportions. Overall mortality was 65% (n = 103); mean ISS = 40; median time to death, 6.1 hours. In univariate analyses, death was not associated with age, sex, or more RBC units transfused beyond 20 but was associated with blunt injury, increasing injury severity, severe head injury, and failure to receive hemostatic blood product ratios. Mortality was also associated with decreased pH and evidence of coagulopathy at admission, especially hypofibrinogenemia. Multivariable logistic regression showed severe head injury, admission hypofibrinogenemia and not receiving a hemostatic resuscitation proportion of blood products as independently associated with death. One in 420 acute trauma patients at our center received UMT, a historically low rate. A third of these patients lived, and UMT was not itself a marker of futility. Early identification of coagulopathy was possible, and failure to give blood components in hemostatic ratios was associated with excess mortality.

Muldowney M ，Liu Z ，Stansbury LG ，Vavilala MS ，Hess JR ... -  《-》

Impact of a calcium replacement protocol during massive transfusion in trauma patients at a level 2 trauma center.

Hypocalcemia is associated with increased mortality in trauma patients with hemorrhagic shock who require massive transfusion protocols (MTPs). Despite known risks of potentiating hypocalcemia with blood product administration, there is little research discussing appropriate calcium replacement. The purpose of this study was to evaluate the ability of a standardized calcium replacement protocol to reduce the incidence of hypocalcemia in trauma patients undergoing MTP. This retrospective, single-center, pre-post study evaluated the use of a calcium replacement protocol during MTP. Adult trauma patients with MTP orders who received at least one "round" of product transfusion were included. Patients were excluded if their ionized calcium (iCa) levels were unavailable or they were transferred to a higher level of care within 4 hours of presentation. The primary outcome was incidence of hypocalcemia (iCa of <1.1 mg/dL) within 24 hours of MTP initiation. Secondary endpoints included the incidence of severe hypocalcemia (iCa of <0.9 mg/dL), time to first calcium dose, total calcium dose administered (mEq), resolution of hypocalcemia within 24 hours, hypercalcemia, adherence to the calcium replacement protocol, and mortality. The incidence of hypocalcemia within 24 hours was significantly lower in the postprotocol group (63% vs 95.2%; P = 0.006). There was not a significant difference in the incidence of severe hypocalcemia between the groups (39.1% vs 69.1%; P = 0.083). Time to first calcium dose was significantly shorter in postprotocol patients compared to preprotocol patients (median [interquartile range], 5.5 [0-21] minutes vs 43 [22.8-73] minutes; P < 0.0001), and postprotocol patients were administered more calcium during MTP (40.8 [27.2-54.4] mEq vs 27.2 [14-32.2] mEq; P = 0.005). Adherence to the protocol was seen in only 37% of patients in the postprotocol group. There was no difference in the rate of adverse events or overall mortality. Trauma patients who received massive transfusion of blood products had a significantly lower incidence of hypocalcemia after a calcium replacement protocol was implemented.

Shandaliy Y ，Busey K ，Scaturo N 《-》

Hypocalcemia in trauma patients receiving massive transfusion.

Massive transfusion protocol (MTP) is increasingly used in civilian trauma resuscitation. Calcium is vital for coagulation, but hypocalcemia commonly occurs during massive transfusion due to citrate and serum calcium chelation. This study was conducted to determine the incidence of hypocalcemia and severe hypocalcemia in trauma patients who receive massive transfusion and to compare characteristics of patients with severe versus nonsevere hypocalcemia. This was a retrospective study of trauma patients who received massive transfusion between January 2009 and November 2013. The primary outcome was the incidence of hypocalcemia (ionized calcium [iCa] < 1.12 mmol/L) and severe hypocalcemia (iCa < 0.90 mmol/L). Secondary outcomes included calcium monitoring, calcium replacement, and correction of coagulopathy. There were 156 patients included; 152 (97%) experienced hypocalcemia, and 111 (71%) had severe hypocalcemia. Patients were stratified into iCa ≥ 0.90 (n = 45) and iCa < 0.90 (n = 111). There were no differences in demographics or baseline laboratories except the severe hypocalcemia group had higher baseline activated partial thromboplastin time (29.7 [23.7-50.9] versus 25.8 [22.3-35.9], P = 0.003), higher lactic acid (5.8 [4.1-9.8] versus 4.0 [3.1-7.8], P = 0.019), lower platelets (176 [108-237] versus 208 [169-272], P = 0.003), and lower pH (7.14 [6.98-7.28] versus 7.23 [7.14-7.33], P = 0.019). Mortality was higher in the severe hypocalcemia group (49% versus 24%, P = 0.007). Patients in the iCa < 0.90 group received more blood products (34 [23-58] versus 22 [18-30] units, P < 0.001), and calcium chloride (4 [2-7] versus 3 [1-4] g, P = 0.002), but there was no difference in duration of MTP or final iCa. Neither group reached a median iCa > 1.12. Hypocalcemia is common during MTP, and vigilant monitoring is warranted. Research is needed to effectively manage hypocalcemia during massive transfusion.

Giancarelli A ，Birrer KL ，Alban RF ，Hobbs BP ，Liu-DeRyke X ... -  《-》