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Background: 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., Methods: 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., Results: 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)., Conclusion: 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., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess if transfusion with low-titer group O whole blood (LTOWB) is associated with improved early and/or late survival compared with component blood product therapy (CT) in bleeding trauma patients., Data Sources: A systematic search of PubMed, CINAHL, and Web of Science was performed from their inception through December 1, 2023. Key terms included injury, hemorrhage, bleeding, blood transfusion, and whole blood., Study Selection: All studies comparing outcomes in injured civilian adults and children who received LTOWB versus CT were included., Data Extraction: Data including author, publication year, sample size, total blood volumes, and clinical outcomes were extracted from each article and reported following the Meta-analysis Of Observational Studies in Epidemiology guidelines. Main outcomes were 24-hour (early) and combined 28-day, 30-day, and in-hospital (late) mortality rates between recipients of LTOWB versus CT, which were pooled using random-effects models., Data Synthesis: Of 1297 studies reviewed, 24 were appropriate for analysis. Total subjects numbered 58,717 of whom 5,164 received LTOWB. Eleven studies included adults-only, seven included both adults and adolescents, and six only included children. The median (interquartile range) age for patients who received LTOWB and CT was 35 years (24-39) and 35.5 years (23-39), respectively. Overall, 14 studies reported early mortality and 22 studies reported late mortality. LTOWB was associated with improved 24-hour survival (risk ratios [RRs] [95% CI] = 1.07 [1.03-1.12]) and late (RR [95% CI] = 1.05 [1.01-1.09]) survival compared with component therapy. There was no evidence of small study bias and all studies were graded as a moderate level of bias., Conclusions: These data suggest hemostatic resuscitation with LTOWB compared with CT improves early and late survival outcomes in bleeding civilian trauma patients. The majority of subjects were injured adults; multicenter randomized controlled studies in injured adults and children are underway to confirm these findings., Competing Interests: Dr. Spinella is a consultant for Cerus and Hemanext, on the advisory board for Haima and Octapharma, and is a Co-Founder and Chief Medical Officer of Kalocyte. He also has funding from Biomedical Advanced Research and Development Authority to perform a trial examining the safety and efficacy of whole blood. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The contribution of the endothelium to trauma-induced coagulopathy has not been thoroughly investigated in injured children., Methods: This is a prospective cohort study of children (younger than 18 years) who presented with a potentially severe injury to an academic pediatric trauma center. Syndecan-1 level was collected on arrival and 24 hours following hospital arrival. Children were categorized as injured versus uninjured based on results of trauma evaluation. Demographics, injury characteristics, vital signs, and clinical laboratories were recorded. A composite clinical outcome was defined as death or blood product transfusion within 24 hours of hospital arrival. Statistical tests determined the impact of injury characteristics and therapeutics on syndecan-1 levels and assessed for associations between syndecan-1 level and outcomes., Results: A total of 121 subjects were included in the analysis: 96 injured (79%) and 25 uninjured (21%). There were no differences between groups in age (median [interquartile range (IQR)], 11 [4-14] years), sex, or race. The injured cohort had a median (IQR) Injury Severity Score of 16 (9-21), 75% had blunt mechanism, 26% were transfused within 6 hours, 3% had 24-hour mortality, and 6% had in-hospital mortality. Median (IQR) syndecan-1 level on admission was significantly higher in injured versus uninjured cohort (44 [21-75] vs. 25 [17-42]; p = 0.04). Admission base deficit was significantly correlated with syndecan-1 level ( r = 0.8, p < 0.001); no association with traumatic brain injury or injury mechanism was seen. Children with elevated syndecan-1 on admission had significantly increased odds of poor outcome; every 10 ng/mL increase in syndecan-1 was associated with 10% increased odds of death or transfusion ( p < 0.001). Transfusion with any blood product was associated with a significant decrease in syndecan-1 from arrival to 24 hours (Δ syndecan-1, -17 [-64 to -5] vs. -8 [-19 to +2]; p < 0001)., Conclusion: Elevated admission syndecan-1 level, suggestive of endotheliopathy, was associated with shock and poor outcomes in pediatric trauma. Larger cohort studies are required to fully describe the complexities of trauma-induced coagulopathy and investigate the benefit of therapies targeting endotheliopathy in children., Level of Evidence: Prognostic and Epidemiological; Level III., (Copyright © 2023 American Association for the Surgery of Trauma.)

Objective: The safety of Low Titer Group O Whole Blood (LTOWB) transfusion has not been well-studied in small children., Methods: This is a single-center retrospective cohort study of pediatric recipients of RhD-LTOWB (June 2016-October 2022) who weigh less than 20 kilograms. Biochemical markers of hemolysis (lactate dehydrogenase, total bilirubin, haptoglobin, and reticulocyte count) and renal function (creatinine and potassium) were recorded on the day of LTOWB transfusion and post-transfusion days 1 and 2. Group O and non-Group O recipients were compared., Results: Twenty-one children were included. Their median (interquartile range [IQR]) weight was 12 kg (12-18) with minimum 2.8 kg, and median (IQR) age was 3 years (1.75-5.00) with minimum 0.08 years (29 days old). The most common indication for transfusion was trauma (17/21; 81%). The median (IQR) volume of LTOWB transfused was 30 mL/kg (20-42). There were 9 non-group O and 12 group O recipients. There were no statistically significant differences in the median concentrations of any of the biochemical markers of hemolysis or the renal function markers between the non-group O and the group O recipients at any of the three time points (p > 0.05 for all comparisons). There were also no statistically significant differences in demographic parameters or clinical outcomes including 28-day mortality, length of stay, ventilator days, and venous thromboembolism between the groups. No transfusion reactions were reported in either group., Conclusion: These data suggest LTOWB use is safe in children weighing less than 20 kg. Further multi-center studies and larger cohorts are needed to confirm these results., (© 2023 AABB.)

Introduction: Thromboelastography (TEG)-derived maximum amplitude-reaction time (MA-R) ratio that accounts for both hypocoagulable and hypercoagulable changes in coagulation is associated with poor outcomes in adults. The relationship between these TEG values and outcomes has not been studied in children., Methods: In a retrospective cohort study, a level I pediatric trauma center database was queried for children younger than 18 years who had a TEG assay on admission between 2016 and 2020. Demographics, injury characteristics, and admission TEG values were recorded. The MA-R ratio was calculated and divided into quartiles. Main outcomes included mortality, transfusion within 24 hours of admission, and thromboembolism. A logistic regression model was generated adjusting for age, Injury Severity Score, injury mechanism, admission shock, and Glasgow Coma Scale., Results: In total, 657 children were included, of which 70% were male and 75% had blunt mechanism injury. The median (interquartile range) age was 11 (4-14) years, the median (interquartile range) Injury Severity Score was10 (5-22), and in-hospital mortality was 7% (n = 45). Of these patients, 17% (n = 112) required transfusion. Most R and MA values were within normal limits. On unadjusted analysis, the lowest MA-R ratio quartile was associated with increased mortality (15% vs. 4%, 5%, and 4%, respectively; p < 0.001) and increased transfusion need (26% vs. 12%, 16%, and 13%, respectively; p = 0.002) compared with higher quartiles. In the logistic regression models, a low MA-R ratio was independently associated with increased in-hospital mortality (odds ratio [95% confidence interval], 4.4 [1.9-10.2]) and increased need for transfusion within 24 hours of admission (odds ratio [95% confidence interval], 2.0 [1.2-3.4]) compared with higher MA-R ratio. There was no association between MA-R ratio and venous thromboembolic events (venous thromboembolic event rate by quartile: 4%, 2%, 1%, and 3%)., Conclusion: Although individual admission TEG values are not commonly substantially deranged in injured children, the MA-R ratio is an independent predictor of poor outcome. Maximum amplitude-reaction time ratio may be a useful prognostic tool in pediatric trauma; validation is necessary., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2022 American Association for the Surgery of Trauma.)

Abstract: Increasing rates of penetrating trauma in the United States makes rapid identification of hemorrhagic shock, coagulopathy, and early initiation of balanced resuscitation in injured children of critical importance. Hemorrhagic shock begins early after injury and can be challenging to identify in children, as hypotension is a late sign that a child is on the verge of circulatory collapse and should be aggressively resuscitated. Recent data support shifting away from crystalloid and toward early resuscitation with blood products because of worse coagulopathy and clinical outcomes in injured patients resuscitated with crystalloid. Multicenter studies have found improved survival in injured children who receive balanced resuscitation with higher fresh frozen plasma: red blood cell ratios. Whole blood is an efficient way to achieve balanced resuscitation in critically injured children with limited intravenous access and decreased exposure to multiple donors. Administration of cold-stored, low-titer O-negative whole blood (LTOWB) appears to be safe in adults and children and may be associated with improved survival in children with life-threatening hemorrhage. Many pediatric centers use RhD-negative LTOWB for all female children because of the risk of hemolytic disease of the fetus and newborn (0-6%); however. there is a scarcity of LTOWB compared with the demand. Low risks of hemolytic disease of the fetus and newborn affecting a future pregnancy must be weighed against high mortality rates in delayed blood product administration in children in hemorrhagic shock. Survey studies involving key stakeholder's opinions on pediatric blood transfusion practices are underway. Existing pediatric-specific literature on trauma resuscitation is often limited and underpowered; multicenter prospective studies are urgently needed to define optimal resuscitation products and practices in injured children in an era of increasing penetrating trauma., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Traumatic hemorrhage is the most common cause of preventable death in civilian and military trauma. Early identification of pediatric life-threatening hemorrhage is challenging. There is no accepted clinical critical administration threshold (CAT) in children for activating massive transfusion protocols., Methods: Children 0 to 17 years old who received any transfusion in the first 24 hours after injury between 2010 and 2019 were included. The type, volume, and time of administration for each product were recorded. The greatest volume of weight-adjusted products transfused within 1 hour was calculated. The cut point for the number of products that maximized sensitivity and specificity to predict in-hospital mortality, need for urgent surgery, and second life-threatening bleeding episode was determined using Youden's index. A binary variable (CAT+) was generated using this threshold for inclusion in a multivariable logistic regression model., Results: In total, 287 patients were included. The median (interquartile range) age was 6 (2-14) years, 60% were males, 83% sustained blunt trauma, and the median (interquartile range) Injury Severity Score was 26 (17-35). The optimal cutoff to define CAT+ was >20 mL/kg of product; this optimized test characteristics for mortality (sensitivity, 70%; specificity, 77%), need for urgent hemorrhage control procedure (sensitivity, 65%; specificity, 74%). and second bleeding episode (sensitivity, 77%; specificity, 74%). There were 93 children (32%) who were CAT+. On multivariate regression, being CAT+ was associated with 3.4 increased odds of mortality (95% confidence interval, 1.67-6.89; p = 0.001) after controlling for age, hypotension, Injury Severity Score, and Glasgow Coma Scale. For every unit of product administered, there was a 10% increased risk of mortality (odds ratio, 1.1; p < 0.001)., Conclusion: Transfusion of more than 20 mL/kg of any blood product within an hour should be used as a threshold for activating massive transfusion protocols in children. Children who meet this CAT are at high risk of mortality and need for interventions; this population may benefit from targeted, timely, and aggressive hemostatic resuscitation., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Low titer group O whole blood (LTOWB) is used as the initial resuscitative fluid in an increasing number of pediatric trauma and massive bleeding transfusion protocols. There is little data on adverse events following its transfusion in pediatric trauma patients., Study Design and Methods: Blood bank records were queried for pediatric recipients of at least one unit of red blood cells (RBCs) (component group) or LTOWB (LTOWB group) within 24 h of admission between May 2013 and August 2020. Subjects with early death (<72 h) were excluded. Propensity-score matching of LTOWB and component groups was performed. Adverse events were recorded, including transfusion reaction, thromboembolism, acute kidney injury, sepsis, and organ failure based on PELOD-2 score, along with hospital and ICU length of stay (LOS) and ventilator days., Results: Thirty-six LTOWB recipients were matched to 36 conventional component recipients. Subjects were 52% male, with blunt injury mechanism (82%), median (IQR) injury severity score = 27 (21-35), and 26% in-hospital mortality. The groups were well matched in terms of demographics and injury characteristics. There were no clinically or statistically significant differences in adverse outcomes including reported transfusion reaction, organ failure, acute kidney injury, sepsis/bacteremia, and venous thromboembolism. Hospital LOS, ventilator days, mortality, and functional disability at discharge were also not significantly different. The LTOWB group had significantly shorter ICU LOS compared to the component group., Conclusion: LTOWB transfusion did not increase the risk of adverse events in children. However, larger studies are required to confirm these results., (© 2021 AABB.)