Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.

Whole Blood and Blood Component Resuscitation in Trauma: Interaction and Association with Mortality.

OBJECTIVE: Evaluate the interaction between whole blood (WB) and blood component resuscitation in relation to mortality following trauma. SUMMARY BACKGROUND DATA: WB is increasingly available in civilian trauma resuscitation, and it is typically transfused concomitantly with blood components. The interaction between WB and blood component transfusions is unclear. METHODS: Adult trauma patients with a shock index >1 who received ≥4 combined units of red blood cells (RBC) or WB within 4 hours across 501 United States trauma centers were included using the American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP) database. The associations between 1)WB resuscitation and mortality, 2)WB to total transfusion volume ratio (WB:TTV) and mortality, 3)balanced blood component transfusion in the setting of combined WB and component resuscitation and mortality were evaluated with multivariable analysis. RESULTS: A total of 12,275 patients were included (WB: 2,884 vs. component-only: 9,391). WB resuscitation was associated with lower odds of 4-hour (adjusted odds ratio [aOR]: 0.81 [0.68-0.97]), 24-hour, and 30-day mortality compared to component-only. Higher WB:TTV ratios were significantly associated with lower 4-hour, 24-hour, and 30-day mortality, with a 13% decrease in odds of 4-hour mortality for each 10% increase in the WB:TTV ratio (0.87 [95%CI:0.80 - 0.94]). Balanced blood component transfusion was associated with significantly lower odds of 4-hour (aOR: 0.45 [95%CI: 0.29 - 0.68]), 24-hour, and 30-day mortality in the setting of combined WB and blood component resuscitation. CONCLUSIONS: WB resuscitation, higher WB:TTV ratios, and balanced blood component transfusion in conjunction with WB were associated with lower mortality in trauma patients presenting in shock requiring 4 units of RBC and/or WB transfusion within 4 hours of arrival.

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

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.

Whole blood: total blood product ratio impacts survival in injured children.

INTRODUCTION: Some studies in both children and adults have shown a mortality benefit for the use of low titer group O whole blood (LTOWB) compared to component therapy for traumatic resuscitation. Although LTOWB is not widely available at pediatric trauma centers, its use is increasing. We hypothesized that in children who received whole blood after injury, the proportion of whole blood in relation to the total blood product resuscitation volume would impact survival. METHODS: The trauma database from a single academic pediatric level 1 trauma center was queried for pediatric (age < 18 years) recipients of LTOWB after injury (years 2015-2022). Weight-based blood product (LTOWB, red blood cells, plasma and platelet) transfusion volumes during the first 24 hours of admission were recorded. The ratio of LTOWB to total transfusion volume was calculated. The primary outcome was in-hospital mortality. Multivariable logistic regression model adjusted for the following variables: age, sex, mechanism of injury, injury severity score, shock index, and Glasgow Coma Scale (GCS) score. Adjusted odds ratio representing the change in the odds of mortality by a 10% increase in the LTOWB:total transfusion volume ratio was reported. RESULTS: There were 95 pediatric LTOWB recipients included in the analysis, with median (IQR) age of 10 years (5-14), 58% male, median (IQR) injury severity score of 26 (17-35), 25% penetrating mechanism. The median(IQR) volume of LTOWB transfused was 17 (15-35) mL/kg. LTOWB comprised a median (IQR) of 59% (33-100) of the total blood product resuscitation. Among patients who received LTOWB, there was a 38% decrease in in-hospital mortality for each 10% increase in the proportion of WB within total transfusion volume (p < 0.001) after adjusting for age, sex, mechanism of injury, injury severity score, shock index, and GCS score. CONCLUSION: Increased proportions of LTOWB within the total blood product resuscitation was independently associated with survival in injured children. Based on existing data that suggests safety and improved outcomes with whole blood, consideration may be given to increasing the use of LTOWB over CT resuscitation in pediatric trauma resuscitation. ARTICLE TYPE: Level 3 Evidence; Observational Cohort Study.

Another piece of the hemolytic disease of the fetus and newborn puzzle after RhD-positive transfusion in trauma resuscitation: the proportion of pregnant women who produce high titer anti-D.

Background: After the transfusion of RhD-positive red blood cell (RBC)-containing products to an RhD-negative woman of childbearing potential (WCP) during trauma resuscitation, there are several events that must occur for that WCP to have a future pregnancy affected by hemolytic disease of the fetus and newborn (HDFN). This study identified and quantitated the frequency of a novel event in the sequence from RhD-positive transfusion during trauma resuscitation to an HDFN outcome, that is, the development of a high titer anti-D among women who were D-alloimmunized. Methods: The transfusion service records at one maternity hospital were searched to locate all anti-D titers that had been performed on pregnant women between 1996 and 2022. The highest titer score during each pregnancy was recorded for this study. The critical titer threshold at this institution was ≥16. Passive anti-D caused by Rh immunoglobulin were excluded from analysis. Results: There were 97 pregnancies in 85 patients who had an immune-stimulated anti-D; in 60 of 97 (62%) pregnancies, the highest titer score was ≥16. There were 12 patients who had titers performed in two pregnancies during the study period; the correlation between the maximum titer in each pregnancy was not statistically significant (Spearman rank correlation r=0.42, p=0.17). Conclusion: In this single center study, 62% of D-alloimmunized pregnant women had a high titer antibody. When considering all of the events that must occur for HDFN to happen, the rate of perinatal mortality was calculated to be 0.04% and the rate of perinatal death or serious adverse event from HDFN was 0.24%.

Use of whole blood in pediatric trauma: a narrative review.

Balanced hemostatic resuscitation has been associated with improved outcomes in patients with both pediatric and adult trauma. Cold-stored, low-titer group O whole blood (LTOWB) has been increasingly used as a primary resuscitation product in trauma in recent years. Benefits of LTOWB include rapid, balanced resuscitation in one product, platelets stored at 4°C, fewer additives and fewer donor exposures. The major theoretical risk of LTOWB transfusion is hemolysis, however this has not been shown in the literature. LTOWB use in injured pediatric populations is increasing but is not yet widespread. Seven studies to date have described the use of LTOWB in pediatric trauma cohorts. Safety of LTOWB use in both group O and non-group O pediatric patients has been shown in several studies, as indicated by the absence of hemolysis and acute transfusion reactions, and comparable risk of organ failure. Reported benefits of LTOWB included faster resolution of shock and coagulopathy, lower volumes of transfused blood products, and an independent association with increased survival in massively transfused patients. Overall, pediatric data are limited by small sample sizes and mostly single center cohorts. Multicenter randomized controlled trials are needed.

Therapeutic plasma exchange is feasible and tolerable in severely injured patients with trauma-induced coagulopathy.

Objectives: Trauma-induced coagulopathy (TIC) occurs in a subset of severely injured trauma patients. Despite having achieved surgical hemostasis, these individuals can have persistent bleeding, clotting, or both in conjunction with deranged coagulation parameters and typically require transfusion support with plasma, platelets, and/or cryoprecipitate. Due to the multifactorial nature of TIC, targeted interventions usually do not have significant clinical benefits. Therapeutic plasma exchange (TPE) is a non-specific modality of removing and replacing a patient's plasma in a euvolemic manner that can temporarily normalize coagulation parameters and remove deleterious substances, and may be beneficial in such patients with TIC. Methods: In a prospective case series, TPE was performed in severely injured trauma patients diagnosed with TIC and transfusion requirement. These individuals all underwent a series of at least 3 TPE procedures performed once daily with plasma as the exclusive replacement fluid. Demographic, injury, laboratory, TPE, and outcome data were collected and analyzed. Results: In total, 7 patients received 23 TPE procedures. All patients had marked improvements in routine coagulation parameters, platelet counts, a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) activities, inflammatory markers including interleukin-6 concentrations, and organ system injuries after completion of their TPE treatments. All-cause mortality rates at 1 day, 7 days, and 30 days were 0%, 0%, and 43%, respectively, and all patients for whom TPE was initiated within 24 hours after injury survived to the 30-day timepoint. Surgical, critical care, and apheresis nursing personnel who were surveyed were universally positive about the utilization of TPE in this patient population. These procedures were tolerated well with the most common adverse event being laboratory-diagnosed hypocalcemia. Conclusion: TPE is feasible and tolerable in severely injured trauma patients with TIC. However, many questions remain regarding the application of TPE for these critically ill patients including identification of the optimal injured population, ideal time of treatment initiation, appropriate treatment intensity, and concurrent use of adjunctive treatments. Level of evidence: Level V.

Endotheliopathy of trauma in children: The association of syndecan-1 with injury and poor outcomes.

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.

Damage-control resuscitation in pediatric trauma: What you need to know.

ABSTRACT: Damage-control resuscitation (DCR) consists of rapid control of bleeding, avoidance of hemodilution, acidosis, and hypothermia; early empiric balanced transfusions with red blood cells, plasma and platelets, or whole blood when available, and the use of intravenous or mechanical hemostatic adjuncts when indicated. The principles used in pediatric and adult trauma patients are quite similar. There are very important recognized physiologic differences in children with traumatic hemorrhagic shock that warrant slight variations in DCR. In pediatric trauma patients, early physiologic signs of shock may be different from adults and the early recognition of this is critical to enable prompt resuscitation and utilization of damage control principles. This review details the current principles of pediatric DCR based on the best available literature, expert consensus recommendations, and also describes a practical guide for implementation of DCR strategies for pediatric trauma patients.

Age-related changes in thromboelastography profiles in injured children.

BACKGROUND: The role of age in mediating coagulation characteristics in injured children is not well defined. We hypothesize thromboelastography (TEG) profiles are unique across pediatric age groups. METHODS: Consecutive trauma patients younger than 18 years from a Level I pediatric trauma center database from 2016 to 2020 with TEG obtained on arrival to the trauma bay were identified. Children were categorized by age according to the National Institute of Child Health and Human Development categories (infant, ≤1 year; toddler, 1-2 years; early childhood, 3-5 years; older childhood, 6-11 years; adolescent, 12-17 years). Thromboelastography values were compared across age groups using Kruskal-Wallis and Dunn's tests. Analysis of covariance was performed controlling for sex, Injury Severity Score (ISS), arrival Glasgow Coma Scale (GCS) score, shock, and mechanism of injury. RESULTS: In total, 726 subjects were identified; 69% male, median (interquartile range [IQR]) ISS = 12 (5-25), and 83% had a blunt mechanism. On univariate analysis, there were significant differences in TEG α-angle ( p < 0.001), MA ( p = 0.004), and fibrinolysis 30 minutes after MA (LY30) ( p = 0.01) between groups. In post hoc tests, the infant group had significantly greater α-angle (median, 77; IQR, 71-79) and MA (median, 64; IQR, 59-70) compared with other groups, while the adolescent group had significantly lower α-angle (median, 71; IQR, 67-74), MA (median, 60; IQR, 56-64), and LY30 (median, 0.8; IQR, 0.2-1.9) compared with other groups. There were no significant differences between toddler, early childhood, and middle childhood groups. On multivariate analysis, the relationship between age group and TEG values (α-angle, MA, and LY30) persisted after controlling for sex, ISS, GCS, shock, and mechanism of injury. CONCLUSION: Age-associated differences in TEG profiles across pediatric age groups exist. Further pediatric-specific research is required to assess whether the unique profiles at extremes of childhood translate to differential clinical outcomes or responses to therapies in injured children. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Prehospital tranexamic acid is associated with a dose-dependent decrease in syndecan-1 after trauma: A secondary analysis of a prospective randomized trial.

BACKGROUND: In the Study of Tranexamic Acid During Air and Ground Prehospital Transport (STAAMP) Trial, prehospital tranexamic acid (TXA) was associated with lower mortality in specific patient subgroups. The underlying mechanisms responsible for a TXA benefit remain incompletely characterized. We hypothesized that TXA may mitigate endothelial injury and sought to assess whether TXA was associated with decreased endothelial or tissue damage markers among all patients enrolled in the STAAMP Trial. METHODS: We collected blood samples from STAAMP Trial patients and measured markers of endothelial function and tissue damage including syndecan-1, soluble thrombomodulin (sTM), and platelet endothelial cell adhesion molecule-1 at hospital admission (0 hours) and 12 hours, 24 hours, and 72 hours after admission. We compared these marker values for patients in each treatment group during the first 72 hours, and modeled the relationship between TXA and marker concentration using regression analysis to control for potential confounding factors. RESULTS: We analyzed samples from 766 patients: 383 placebo, 130 abbreviated dosing, 119 standard dosing, and 130 repeat dosing. Lower levels of syndecan-1, TM, and platelet endothelial cell adhesion molecule measured within the first 72 hours of hospital admission were associated with survival at 30 days ( p < 0.001). At hospital admission, syndecan-1 was lower in the TXA group (28.30 [20.05, 42.75] vs. 33.50 [23.00, 54.00] p = 0.001) even after controlling for patient, injury, and prehospital factors ( p = 0.001). For every 1 g increase in TXA administered over the first 8 hours of prehospital transport and hospital admission, there was a 4-ng/mL decrease in syndecan-1 at 12 hours controlling for patient, injury, and treatment factors ( p = 0.03). CONCLUSION: Prehospital TXA was associated with decreased syndecan-1 at hospital admission. Syndecan-1 measured 12 hours after admission was inversely related to the dose of TXA received. Early prehospital and in-hospital TXA may decrease endothelial glycocalyx damage or upregulate vascular repair mechanisms in a dose-dependent fashion. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Epsilon aminocaproic acid is associated with acute kidney injury after life-threatening hemorrhage in children.

BACKGROUND: Antifibrinolytic medications have been associated with reduced mortality in pediatric hemorrhage but may contribute to adverse events such as acute kidney injury (AKI). STUDY DESIGN AND METHODS: We conducted a secondary analysis of the MAssive Transfusion in Children (MATIC), a prospectively collected database of children with life-threatening hemorrhage (LTH), and evaluated for risk of adverse events with either antifibrinolytic treatment, epsilon aminocaproic acid (EACA) or tranexamic acid (TXA). The primary outcome was AKI and secondary outcomes were acute respiratory distress syndrome (ARDS) and sepsis. RESULTS: Of 448 children included, median (interquartile range) age was 7 (2-15) years, 55% were male, and LTH etiology was 46% trauma, 34% operative, and 20% medical. Three hundred and ninety-three patients did not receive an antifibrinolytic (88%); 37 (8%) received TXA and 18 (4%) received EACA. Sixty-seven (17.1%) patients in the no antifibrinolytic group developed AKI, 6 (16.2%) patients in the TXA group, and 9 (50%) patients in the EACA group (p = .002). After adjusting for cardiothoracic surgery, cyanotic heart disease, preexisting renal disease, lowest hemoglobin pre-LTH, and total weight-adjusted transfusion volume during the LTH, the EACA group had increased risk of AKI (adjusted odds ratio 3.3 [95% CI: 1.0-10.3]) compared to no antifibrinolytic. TXA was not associated with AKI. Neither antifibrinolytic treatment was associated with ARDS or sepsis. CONCLUSION: Administration of EACA during LTH may increase the risk of AKI. Additional studies are needed to compare the risk of AKI between EACA and TXA in pediatric patients.

Admission maximum amplitude-reaction time ratio: Association between thromboelastography values predicts poor outcome in injured children.

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.

Recognizing life-threatening bleeding in pediatric trauma: A standard for when to activate massive transfusion protocol.

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.

Resuscitative practices and the use of low-titer group O whole blood in pediatric 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.

Pediatric traumatic hemorrhagic shock consensus conference research priorities.

BACKGROUND: Traumatic injury is the leading cause of death in children and adolescents. Hemorrhagic shock remains a common and preventable cause of death in the pediatric trauma patients. A paucity of high-quality evidence is available to guide specific aspects of hemorrhage control in this population. We sought to identify high-priority research topics for the care of pediatric trauma patients in hemorrhagic shock. METHODS: A panel of 16 consensus multidisciplinary committee members from the Pediatric Traumatic Hemorrhagic Shock Consensus Conference developed research priorities for addressing knowledge gaps in the care of injured children and adolescents in hemorrhagic shock. These ideas were informed by a systematic review of topics in this area and a discussion of these areas in the consensus conference. Research priorities were synthesized along themes and prioritized by anonymous voting. RESULTS: Eleven research priorities that warrant additional investigation were identified by the consensus committee. Areas of proposed study included well-designed clinical trials and evaluations, including increasing the speed and accuracy of identifying and treating hemorrhagic shock, defining the role of whole blood and tranexamic acid use, and assessment of the utility and appropriate use of viscoelastic techniques during early resuscitation. The committee recommended the need to standardize essential definitions, data elements, and data collection to facilitate research in this area. CONCLUSION: Research gaps remain in many areas related to the care of hemorrhagic shock after pediatric injury. Addressing these gaps is needed to develop improved evidence-based recommendations for the care of pediatric trauma patients in hemorrhagic shock.

Pediatric traumatic hemorrhagic shock consensus conference recommendations.

ABSTRACT: Hemorrhagic shock in pediatric trauma patients remains a challenging yet preventable cause of death. There is little high-quality evidence available to guide specific aspects of hemorrhage control and specific resuscitation practices in this population. We sought to generate clinical recommendations, expert consensus, and good practice statements to aid providers in care for these difficult patients.The Pediatric Traumatic Hemorrhagic Shock Consensus Conference process included systematic reviews related to six subtopics and one consensus meeting. A panel of 16 consensus multidisciplinary committee members evaluated the literature related to 6 specific topics: (1) blood products and fluid resuscitation for hemostatic resuscitation, (2) utilization of prehospital blood products, (3) use of hemostatic adjuncts, (4) tourniquet use, (5) prehospital airway and blood pressure management, and (6) conventional coagulation tests or thromboelastography-guided resuscitation. A total of 21 recommendations are detailed in this article: 2 clinical recommendations, 14 expert consensus statements, and 5 good practice statements. The statement, the panel's voting outcome, and the rationale for each statement intend to give pediatric trauma providers the latest evidence and guidance to care for pediatric trauma patients experiencing hemorrhagic shock. With a broad multidisciplinary representation, the Pediatric Traumatic Hemorrhagic Shock Consensus Conference systematically evaluated the literature and developed clinical recommendations, expert consensus, and good practice statements concerning topics in traumatically injured pediatric patients with hemorrhagic shock.

Low Titer Group O Whole Blood In Injured Children Requiring Massive Transfusion.

OBJECTIVE: The aim of this study was to assess the survival impact of low-titer group O whole blood (LTOWB) in injured pediatric patients who require massive transfusion. SUMMARY BACKGROUND DATA: Limited data are available regarding the effectiveness of LTOWB in pediatric trauma. METHODS: A prospective observational study of children requiring massive transfusion after injury at UPMC Children's Hospital of Pittsburgh, an urban academic pediatric Level 1 trauma center. Injured children ages 1 to 17 years who received a total of >40 mL/kg of LTOWB and/or conventional components over the 24 hours after admission were included. Patient characteristics, blood product utilization and clinical outcomes were analyzed using Kaplan-Meier survival curves, log rank tests and Cox proportional hazards regression analyses. The primary outcome was 28-day survival. RESULTS: Of patients analyzed, 27 of 80 (33%) received LTOWB as part of their hemostatic resuscitation. The LTOWB group was comparable to the component therapy group on baseline demographic and physiologic parameters except older age, higher body weight, and lower red blood cell and plasma transfusion volumes. After adjusting for age, total blood product volume transfused in 24 hours, admission base deficit, international normalized ratio (INR), and injury severity score (ISS), children who received LTOWB as part of their resuscitation had significantly improved survival at both 72 hours and 28 days post-trauma [adjusted odds ratio (AOR) 0.23, P = 0.009 and AOR 0.41, P = 0.02, respectively]; 6-hour survival was not statistically significant (AOR = 0.51, P = 0.30). Survivors at 28 days in the LTOWB group had reduced hospital LOS, ICU LOS, and ventilator days compared to the CT group. CONCLUSION: Administration of LTOWB during the hemostatic resuscitation of injured children requiring massive transfusion was independently associated with improved 72-hour and 28-day survival.

Characterization of immediate and early mortality after repair of ruptured abdominal aortic aneurysm.

BACKGROUND: We sought to compare immediate and early mortality among patients undergoing ruptured abdominal aortic aneurysm (RAAA) repair. Evaluation of RAAA has focused on 30-day postoperative mortality. Other emergency conditions such as trauma have demonstrated a multimodal mortality distribution within the 30-day window, expanding the pathophysiologic understanding and allowing for intervention investigations with practice changing and lifesaving results. However, the temporal distribution and risk factors of postoperative morbidity and mortality in RAAA have yet to be investigated. METHODS: We evaluated factors associated with RAAA postoperative mortality in immediate (<1 day) and early (1-30 days) postoperative periods in a landmarked retrospective cohort study using data from the Vascular Quality Initiative (2010-2020). RESULTS: We identified 5157 RAAA repairs (mean age, 72 ± 10 years; 77% male; 88% White; 61% endovascular). The mortality rate in the immediate period was 10.2% (528/5157) and the early mortality rate was 22.1% (918/4163). In multivariable regression analyses, signs of hemorrhagic shock (ie, hemoglobin <7 g/dL: adjusted odds ratio [aOR], 1.87 [95% confidence interval [CI], 1.14-3.06]; any preoperative systolic blood pressure <70 mm Hg: aOR, 1.40 [95% CI, 1.04-1.89]; and estimated blood loss >40%: aOR, 3.65 [95% CI, 2.29-5.83]) were associated with an increased risk of immediate mortality. Comorbid conditions (heart failure: aOR, 1.38 [95% CI, 1.00-1.92]; pulmonary disease: aOR, 1.29 [95% CI, 1.05-1.58]; elevated creatinine: aOR 1.26 [95% CI, 1.31-1.41]) were associated with increased risk of early mortality. CONCLUSIONS: Immediate deaths were associated predominantly with shock from massive hemorrhage, whereas early deaths were associated with comorbid conditions predisposing patients to multisystem organ failure despite successful repair. These temporal distinctions should guide future mechanistic and intervention evaluations to improve RAAA mortality.

Sex dimorphisms in coagulation characteristics in the pediatric trauma population appear after puberty.

BACKGROUND: The role of age and sex in mediating coagulation characteristics in injured children is not well defined. We hypothesize that thromboelastography (TEG) profiles are equivalent across sex in younger children and diverge after puberty. METHODS: Consecutive trauma patients younger than 18 years were identified from a university-affiliated, Level I, pediatric trauma center (2016-2020) database. Demographics, injury characteristics, and TEG parameters were recorded. Children were categorized by sex and age (younger, ≤10 years; older, ≥11 years). Baseline characteristics, outcomes, and TEG parameters were compared using nonparametric tests as appropriate. To account for the effects of confounding variables, analysis of covariance was performed controlling for Injury Severity Score (ISS), admission Glasgow Coma Scale score, and pediatric age-adjusted shock index. RESULTS: Six hundred forty-seven subjects were identified (70.2% male, median ISS, 10; interquartile range, 5-24; blunt mechanism, 75.4%). Among 395 younger children (≤10 years), there were no differences in TEG characteristics between sexes. Among 252 adolescents (≥11 years), males had greater kinetic times (1.8 vs. 1.4 min; p < 0.001), decreased alpha angles (69.6° vs73.7°; p < 0.001), and lower maximum amplitudes (59.4 vs. 61.5 mm; p = 0.01). Fibrinolysis was significantly lower in older females compared with younger females (0.4% vs. 1.5%, p < 0.001) and age-matched males (0.4% vs. 1.0%, p = 0.02). Compared with younger male children, adolescent males had greater kinetic times (1.8 vs. 1.4 min; p < 0.001), decreased alpha angles (73.5° vs. 69.6°, p < 0.001), lower maximum amplitudes (59.4 vs. 62 mm, p < 0.001), and less fibrinolysis (1.0% vs. 1.3%, p = 0.03). This interaction persisted after controlling for ISS, Glasgow Coma Scale, and pediatric age-adjusted shock index. CONCLUSION: Sex dimorphisms in TEG coagulation profiles appear after puberty. This divergence appears to be driven by a shift in male coagulation profiles to a relatively hypocoagulable state and female coagulation profiles to a relatively hypercoagulable state after puberty. LEVEL OF EVIDENCE: Prognostic and Epidemiologic, Level III.