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ImportanceIt is not clear which severely injured patients with hemorrhagic shock may benefit most from a 1:1:1 vs 1:1:2 (plasma:platelets:red blood cells) resuscitation strategy. Identification of trauma molecular endotypes may reveal subgroups of patients with differential treatment response to various resuscitation strategies.ObjectiveTo derive trauma endotypes (TEs) from molecular data and determine whether these endotypes are associated with mortality and differential treatment response to 1:1:1 vs 1:1:2 resuscitation strategies.Design, Setting, and ParticipantsThis was a secondary analysis of the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) randomized clinical trial. The study cohort included individuals with severe injury from 12 North American trauma centers. The cohort was taken from the participants in the PROPPR trial who had complete plasma biomarker data available. Study data were analyzed on August 2, 2021, to October 25, 2022.ExposuresTEs identified by K-means clustering of plasma biomarkers collected at hospital arrival.Main Outcomes and MeasuresAn association between TEs and 30-day mortality was tested using multivariable relative risk (RR) regression adjusting for age, sex, trauma center, mechanism of injury, and injury severity score (ISS). Differential treatment response to transfusion strategy was assessed using an RR regression model for 30-day mortality by incorporating an interaction term for the product of endotype and treatment group adjusting for age, sex, trauma center, mechanism of injury, and ISS.ResultsA total of 478 participants (median [IQR] age, 34.5 [25-51] years; 384 male [80%]) of the 680 participants in the PROPPR trial were included in this study analysis. A 2-class model that had optimal performance in K-means clustering was found. TE-1 (n = 270) was characterized by higher plasma concentrations of inflammatory biomarkers (eg, interleukin 8 and tumor necrosis factor α) and significantly higher 30-day mortality compared with TE-2 (n = 208). There was a significant interaction between treatment arm and TE for 30-day mortality. Mortality in TE-1 was 28.6% with 1:1:2 treatment vs 32.6% with 1:1:1 treatment, whereas mortality in TE-2 was 24.5% with 1:1:2 treatment vs 7.3% with 1:1:1 treatment (P for interaction = .001).Conclusions and RelevanceResults of this secondary analysis suggest that endotypes derived from plasma biomarkers in trauma patients at hospital arrival were associated with a differential response to 1:1:1 vs 1:1:2 resuscitation strategies in trauma patients with severe injury. These findings support the concept of molecular heterogeneity in critically ill trauma populations and have implications for tailoring therapy for patients at high risk for adverse outcomes.

Trauma-induced coagulopathy is a continuum ranging from hypercoagulable to hypercoagulable phenotypes. In single-center studies, the maximum amplitude (MA) to r-time (R) (MA-R) ratio has identified a phenotype of injured patients with high mortality risk. The purpose of this study was to determine the relationship between MA-R and mortality using multicenter data and to investigate fibrinogen consumption in the development of this specific coagulopathy phenotype.Using the Pragmatic Randomized Optimal Platelet and Plasma Ratios data set, patients were divided into blunt and penetrating injury cohorts. MA was divided by R time from admission thromboelastogram to calculate MA-R. MA-R was used to assess odds of early and late mortality using multivariable models. Multivariable models were used to assess thrombogram values in both cohorts. Refinement of the MA-R cut point was performed with Youden index. Repeat multivariable analysis was performed with a binary CRITICAL and NORMAL MA-R.In initial analysis, MA-R quartiles were not associated with mortality in the penetrating cohort. In the blunt cohort, there was an association between low MA-R and early and late mortality. A refined cut point of 11 was identified (CRITICAL: MA-R, ≤11; NORMAL: MA-R,11). CRITICAL MA-R was associated with mortality in both penetrating and blunt subgroups. In further injury subgroup analysis, CRITICAL patients had significantly decreased fibrinogen levels in the blunt subgroup only. In both blunt and penetrating injury, there was no difference in time to initiation of thrombin burst (lagtime). However, both endogenous thrombin potential and peak thrombin levels were significantly lower in CRITICAL patients.MA-R identifies a trauma-induced coagulopathy phenotype characterized in blunt injury by impaired thrombin generation that is associated with early and late mortality. The endotheliopathy and tissue factor release likely plays a role in the cascade of impaired thrombin burst, possible early fibrinogen consumption and the weaker clot identified by MA-R.Therapeutic/care management, level II.

Supplemental digital content is available in the text., BACKGROUND Damage-control resuscitation (DCR) improves survival in severely bleeding patients. However, deviating from balanced transfusion ratios during a resuscitation may limit this benefit. We hypothesized that maintaining a balanced resuscitation during DCR is independently associated with improved survival. METHODS This was a secondary analysis of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. Patients receiving >3 U of packed red blood cells (PRBCs) during any 1-hour period over the first 6 hours and surviving beyond 30 minutes were included. Linear regression assessed the effect of percent time in a high-ratio range on 24-hour survival. We identified an optimal ratio and percent of time above the target ratio threshold by Youden’s index. We compared patients with a 6-hour ratio above the target and above the percent time threshold (on-target) with all others (off-target). Kaplan-Meier analysis assessed the combined effect of blood product ratio and percent time over the target ratio on 24-hour and 30-day survival. Multivariable logistic regression identified factors independently associated with 24-hour and 30-day survival. RESULTS Of 1,245 PROMMTT patients, 524 met the inclusion criteria. Optimal targets were plasma/PRBC and platelet/PRBC of 0.75 (3:4) and ≥40% time spent over this threshold. For plasma/PRBC, on-target (n = 213) versus off-target (n = 311) patients were younger (median, 31 years; interquartile range, [22–50] vs. 40 [25–54]; p = 0.002) with similar injury burdens and presenting physiology. Similar patterns were observed for platelet/PRBC on-target (n = 116) and off-target (n = 408) patients. After adjusting for differences, on-target plasma/PRBC patients had significantly improved 24-hour (odds ratio, 2.25; 95% confidence interval, 1.20–4.23) and 30-day (odds ratio, 1.97; 95% confidence interval, 1.14–3.41) survival, while on-target platelet/PRBC patients did not. CONCLUSION Maintaining a high ratio of plasma/PRBC during DCR is independently associated with improved survival. Performance improvement efforts and prospective studies should capture time spent in a high-ratio range. LEVEL OF EVIDENCE Epidemiologic/prognostic study, level II; Therapeutic, level IV.

Background Several options exist for induction agents during rapid sequence intubation (RSI) in trauma patients, including etomidate, ketamine, and propofol. These drugs have reported variable hemodynamic effects (hypotension with propofol and sympathomimetic effects with ketamine) that could affect trauma resuscitations. The purpose of this study was to compare the hemodynamic effects of these three induction agents during emergency department RSI in adult trauma. We hypothesized that these drugs would display a differing hemodynamic profile during RSI. Methods We performed a retrospective (2014-2019), multicenter trial of adult (≥18 years) trauma patients admitted to eight ACS-verified Level I trauma centers who underwent emergency department RSI. Variables collected included systolic blood pressure (SBP) and pulse before and after RSI. The primary outcomes were change in heart rate and SBP before and after RSI. Results There were 2,092 patients who met criteria, 85% received etomidate (E), 8% ketamine (K), and 7% propofol (P). Before RSI, the ketamine group had a lower SBP (E, 135 vs. K, 125 vs. P, 135 mm Hg, p = 0.04) but there was no difference in pulse (E, 104 vs. K, 107 vs. P, 105 bpm, p = 0.45). After RSI, there were no differences in SBP (E, 135 vs. K, 130 vs. P, 133 mm Hg, p = 0.34) or pulse (E, 106 vs. K, 110 vs. P, 104 bpm, p = 0.08). There was no difference in the average change of SBP (E, 0.2 vs. K, 5.2 vs. P, -1.8 mm Hg, p = 0.4) or pulse (E, 1.7 vs. K, 3.5 bpm vs. P, -0.96, p = 0.24) during RSI. Conclusion Contrary to our hypothesis, there was no difference in the hemodynamic effect for etomidate versus ketamine versus propofol during RSI in trauma patients. Level of evidence Therapeutic, Level IV.

IMPORTANCE: Venous thromboembolism (VTE) affects 2% to 20% of recovering trauma patients, despite aggressive prophylaxis with enoxaparin. Antithrombin is a primary circulating anticoagulant and crucial component of enoxaparin thromboprophylaxis. Approximately 20% of trauma patients present with antithrombin deficiency (antithrombin activity

Objective To describe the current use of the ER-REBOA catheter and associated outcomes and complications. Introduction Noncompressible truncal hemorrhage is the leading cause of potentially preventable death in trauma patients. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a novel strategy to obtain earlier temporary hemorrhage control, supporting cardiac, and cerebral perfusion before definitive hemostasis. Methods Prospective, observational study conducted at 6 Level 1 Trauma Centers over 12-months. Inclusion criteria were age >15 years of age with evidence of truncal hemorrhage below the diaphragm and decision for emergent hemorrhage control intervention within 60 minutes of arrival. REBOA details, demographics, mechanism of injury, complications, and outcomes were collected. Results A total of 8166 patients were screened for enrollment. In 75, REBOA was utilized for temporary hemorrhage control. Blunt injury occurred in 80% with a median injury severity score (ISS) 34 (21, 43). Forty-seven REBOAs were placed in Zone 1 and 28 in Zone 3. REBOA inflation increased systolic blood pressure from 67 (40, 83) mm Hg to 108 (90, 128) mm Hg 5 minutes after inflation (P = 0.02). Cardiopulmonary resuscitation was ongoing during REBOA insertion in 17 patients (26.6%) and 10 patients (58.8%) had return of spontaneous circulation after REBOA inflation. The procedural complication rate was 6.6%. Overall mortality was 52%. Conclusion REBOA can be used in blunt and penetrating trauma patients, including those in arrest. Balloon inflation uniformly improved hemodynamics and was associated with a 59% rate of return of spontaneous circulation for patients in arrest. Use of the ER-REBOA catheter is technically safe with a low procedural complication rate.

Women are underrepresented in trauma research, and aggregated results of clinical trials may mask effects that differ by sex. It is unclear whether women respond differently to severe hemorrhage compared with men. We sought to evaluate sex-based differences in outcomes after severe trauma with hemorrhage.We performed a secondary analysis of the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial. Trauma patients predicted to require massive transfusion were randomized to a 1:1:1 vs 1:1:2 plasma to platelet to red blood cell transfusion ratio. Analysis was performed according to sex, controlling for clinical characteristics and transfusion arm.A total of 134 women and 546 men were analyzed. In multivariable analysis, there was no difference in mortality at 24 hours (hazard ratio for women 0.64, 95% confidence interval 0.34-1.23, P = .18) or in time to hemostasis (hazard ratio 1.10, 95% confidence interval 0.84-1.42, P = .49) by sex. We observed no difference between sexes in volume of blood products transfused during active hemorrhage. However, after anatomic hemostasis, women received lower volumes of all products, with a 38% reduction in fresh frozen plasma (mean ratio 0.62 (95% confidence interval 0.43-0.89, P = .01), 49% reduction in platelets (mean ratio 0.51, 95% confidence interval 0.33-0.79, P.01) and 49% reduction in volume of red blood cells (mean ratio 0.51, 95% confidence interval 0.33-0.79, P.01).Mortality and time to hemostasis of trauma patients with hemorrhage did not differ by sex. Although there was no difference in transfusion requirement during active hemorrhage, once hemostasis was achieved, women received fewer units of all blood products than men. Further research is required to determine whether women exhibit differences in coagulation during and after severe traumatic hemorrhage.

Study objective The transfusion of older packed RBCs may be harmful in critically ill patients. We seek to determine the association between packed RBC age and mortality among trauma patients requiring massive packed RBC transfusion. Methods We analyzed data from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. Subjects in the parent trial included critically injured adult patients admitted to 1 of 12 North American Level I trauma centers who received at least 1 unit of packed RBCs and were predicted to require massive blood transfusion. The primary exposure was volume of packed RBC units transfused during the first 24 hours of hospitalization, stratified by packed RBC age category: 0 to 7 days, 8 to 14 days, 15 to 21 days, and greater than or equal to 22 days. The primary outcome was 24-hour mortality. We evaluated the association between transfused volume of each packed RBC age category and 24-hour survival, using random-effects logistic regression, adjusting for total packed RBC volume, patient age, sex, race, mechanism of injury, Injury Severity Score, Revised Trauma Score, clinical site, and trial treatment group. Results The 678 patients included in the analysis received a total of 8,830 packed RBC units. One hundred patients (14.8%) died within the first 24 hours. On multivariable analysis, the number of packed RBCs greater than or equal to 22 days old was independently associated with increased 24-hour mortality (adjusted odds ratio [OR] 1.05 per packed RBC unit; 95% confidence interval [CI] 1.01 to 1.08): OR 0.97 for 0 to 7 days old (95% CI 0.88 to 1.08), OR 1.04 for 8 to 14 days old (95% CI 0.99 to 1.09), and OR 1.02 for 15 to 21 days old (95% CI 0.98 to 1.06). Results of sensitivity analyses were similar only among patients who received greater than or equal to 10 packed RBC units. Conclusion Increasing quantities of older packed RBCs are associated with increased likelihood of 24-hour mortality in trauma patients receiving massive packed RBC transfusion (≥10 units), but not in those who receive fewer than 10 units.

Focused assessment with sonography for trauma (FAST) performance metrics are unknown in patients with non-compressible torso hemorrhage (NCTH).Retrospective review of a dedicated NCTH database from four level 1 trauma centers (2008-2012). NCTH was defined as (1) named axial torso vessel disruption; (2) AIS chest or abdomen2 with shock (base deficit -4) or truncal operation in ≤ 90 min; or (3) pelvic fracture with ring disruption. Patients were grouped by cavity of hemorrhage source and by shock (SBP ≤ 90).274 patients had a FAST prior to diagnosis of NCTH. FAST was positive in 51% of patients with abdominal/pelvic hemorrhage for a false negative rate (FNR) of 49%. FNR was higher for pelvic (61%) versus abdominal (43%) sources (p = 0.02). There was no difference between FAST negative or positive patients for ISS, shock, length of stay, or mortality (all p = NS). FNR was not improved among the subgroup of NCTH patients with shock (p = NS).FAST identified abdominal/pelvic hemorrhage in approximately half of NCTH patients, and this was not improved among patients presenting with shock.

Clinicians intuitively recognize that faster time to hemostasis is important in bleeding trauma patients, but these times are rarely reported.Prospectively collected data from the Pragmatic Randomized Optimal Platelet and Plasma Ratios trial were analyzed. Hemostasis was predefined as no intraoperative bleeding requiring intervention in the surgical field or resolution of contrast blush on interventional radiology (IR). Patients who underwent an emergent (within 90 minutes) operating room (OR) or IR procedure were included. Mixed-effects Poisson regression with robust error variance (controlling for age, Injury Severity Score, treatment arm, injury mechanism, base excess on admission [missing values estimated by multiple imputation], and time to OR/IR as fixed effects and study site as a random effect) with modified Bonferroni corrections tested the hypothesis that decreased time to hemostasis was associated with decreased mortality and decreased incidence of acute kidney injury (AKI), acute respiratory distress syndrome (ARDS), multiple-organ failure (MOF), sepsis, and venous thromboembolism.Of 680 enrolled patients, 468 (69%) underwent an emergent procedure. Patients with decreased time to hemostasis were less severely injured, had less deranged base excess on admission, and lower incidence of blunt trauma (all p0.05). In 408 (87%) patients in whom hemostasis was achieved, every 15-minute decrease in time to hemostasis was associated with decreased 30-day mortality (RR, 0.97; 95% confidence interval [CI], 0.94-0.99), AKI (RR, 0.97; 95% CI, 0.96-0.98), ARDS (RR, 0.98; 95% CI, 0.97-0.99), MOF (RR, 0.94; 95% CI, 0.91-0.97), and sepsis (RR, 0.98; 95% CI, 0.96-0.99), but not venous thromboembolism (RR, 0.99; 95% CI, 0.96-1.03).Earlier time to hemostasis was independently associated with decreased incidence of 30-day mortality, AKI, ARDS, MOF, and sepsis in bleeding trauma patients. Time to hemostasis should be considered as an endpoint in trauma studies and as a potential quality indicator.Therapeutic/care management, level III.

BACKGROUND The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial showed that 15% of patients developed venous thromboembolism (VTE) following hemorrhage, but the mechanisms are unknown. Since inflammation is associated with hypercoagulability and thrombosis, our goal was to compare the temporal inflammatory profile following hemorrhagic shock in patients with and without VTE. STUDY DESIGN Secondary analysis was performed on data collected from PROPPR. Blood samples collected at 0 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours following admission were assayed on a 27-target cytokine panel, and compared between VTE (n = 83) and non-VTE (n = 475) patients. p < 0.05 indicated significance. RESULTS Over time, both groups exhibited elevations in proinflammatory mediators interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor 57, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1β, and anti-inflammatory mediators IL-1ra and IL-10 (p < 0.05 vs. admission). Venous thromboembolism patients showed amplified responses for IL-6 (6-72 hours) and IL-8 (6-24 hours), which peaked at later time points, and granulocyte colony-stimulating factor 57 (12-24 hours), monocyte chemoattractant protein 1 (6-72 hours), and macrophage inflammatory protein-1 β (2-12 hours) (p < 0.05 vs. non-VTE per time point) that peaked at similar time points to non-VTE patients. The anti-inflammatory responses were similar between groups, but the interleukin-mediated proinflammatory responses continued to rise after the peak anti-inflammatory response in the VTE group. The occurrence rate of adverse events was higher in VTE (97%) versus non-VTE (87%, p = 0.009) and was associated with higher inflammation. CONCLUSION Patients with VTE following hemorrhagic shock exhibited a prolonged and amplified proinflammatory responses mediated by select interleukin, chemotactic, and glycoprotein cytokines that are not antagonized by anti-inflammatory mediators. This response is not related to randomization group, injury severity or degree of shock, but may be linked to adverse events. LEVEL OF EVIDENCE Prognostic, level III.

Background Both groups A and AB plasma have been approved for emergency-release transfusion in acutely bleeding trauma patients before blood grouping being performed. The safety profile associated with this practice has not been well characterized, particularly in patients requiring massive transfusion. Methods This secondary analysis of the Pragmatic, Randomized, Optimal Platelet and Plasma Ratios trial examined whether exposure to group A emergency-release plasma (ERP) was noninferior to group AB ERP. We also examined patients whose blood groups were compatible with group A ERP versus patients whose blood groups were incompatible with group A ERP. Outcomes included 30-day mortality and complication rates including systemic inflammatory response syndrome, infection, renal injury, pulmonary dysfunction, and thromboembolism. Results Of the 680 patients predicted to receive a massive transfusion, 584 (85.9%) received at least 1 U of ERP. Of the 584 patients analyzed, 462 (79.1%) received group AB and 122 (20.9%) received group A ERP. Using a hazard ratio (HR) of 1.35 as the noninferiority margin, transfusion with group A versus group AB ERP was not associated with increased thromboembolic rates (HR, 0.52; 95% confidence interval [CI], 0.31-0.90). Mortality (HR, 1.15; 95% CI, 0.91-1.45) and nonfatal complication rates (HR, 1.24; 95% CI, 0.87-1.77) were inconclusive. In the subgroup analysis, transfusion with incompatible ERP (group B or AB patients receiving group A ERP) was not associated with increased nonfatal complications (HR, 1.02; 95% CI, 0.80-1.30). There were no reported hemolytic transfusion reactions. Conclusion The use of ERP is common in patients requiring massive transfusion and facilitates the rapid balanced resuscitation of patients who have sustained blood loss. Group A ERP is an acceptable option for patients requiring massive transfusion, especially if group AB ERP is not readily available. Level of evidence Therapeutic/Care Management, level IV; Prognostic, level III.

Background Massive transfusion protocols to treat postinjury hemorrhage are based on predefined blood product transfusion ratios followed by goal-directed transfusion based on patient's clinical evolution. However, it remains unclear how these transfusion ratios impact patient outcomes over time from injury. Methods The Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) is a phase 3, randomized controlled trial, across 12 Level I trauma centers in North America. From 2012 to 2013, 680 severely injured patients required massive transfusion. We used semiparametric machine learning techniques and causal inference methods to augment the intent-to-treat analysis of PROPPR, estimating the dynamic relationship between transfusion ratios and outcomes: mortality and hemostasis at different timepoints during the first 24 hours after admission. Results In the intention-to-treat analysis, the 1:1:1 group tended to have decreased mortality, but with no statistical significance. For patients in whom hemostasis took longer than 2 hours, the 1:1:1 ratio was associated with a higher probability of hemostasis, statistically significant from the 4 hour on. In the per-protocol, actual-transfusion-ratios-received analysis, during four successive time intervals, no significant association was found between the actual ratios and mortality. When comparing patient groups who received both high plasma/PRBC and high platelet/PRBC ratios to the group of low ratios in both, the relative risk of achieving hemostasis was 2.49 (95% confidence interval, 1.19-5.22) during the third hour after admission, suggesting a significant beneficial impact of higher transfusion ratios of plasma and platelets on hemostasis. Conclusion Our results suggest that the impact of transfusion ratios on hemostasis is dynamic. Overall, the transfusion ratios had no significant impact on mortality over time. However, receiving higher ratios of platelets and plasma relative to red blood cells hastens hemostasis in subjects who have yet to achieve hemostasis within 3 hours after hospital admission. Level of evidence Therapeutic IV.

To address deficiencies associated with the classic definition of massive transfusion (MT), critical administration threshold (CAT) and resuscitation intensity (RI) were developed to better quantify the overall severity of illness and predict the need for transfusions and early mortality. We sought to evaluate these as more appropriate replacements for MT in defining mortality risk in patients undergoing major transfusions.Patients predicted to receive MT at 12 Level I trauma centers were randomized in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial. MT of 10 U or greater red blood cell (RBC) in 24 hours; CAT+, 3 U or greater RBC in the first hour; and RI, total products in the first 30 minutes (1 U RBC, 1 U plasma, 1000 mL crystalloid, 500 mL colloid each valued at 1 U). Resuscitation intensity was evaluated as a continuous variable and dichotomized as RI4+, where RI is 4 U or greater. Each metric was evaluated for its ability to predict mortality at 3 hours, 6 hours, and 24 hours, and at 30 days.Of the 680 patients, 301 patients met MT definition, 521 were CAT+, and 445 were RI4+. Of those that died, 23% never reached MT threshold, but all were captured by CAT+ and RI4+. The 3-hour (9% vs. 9%), 6-hour (14% vs. 14%), 24-hour (17% vs. 18%), and 30-day mortality rates (28% vs. 29%) were similar between CAT+ and RI4+ patients. When RI was evaluated as a continuous variable, each unit increase was associated with a 20% increase in hemorrhage-related mortality (odds ratio, 1.20; 95% confidence interval, 1.15-1.29; p0.05).Both RI and CAT are valid surrogates for early mortality in patients undergoing major transfusion, capturing patients omitted by the MT definition. The CAT+ showed the best sensitivity; RI4+ demonstrated better specificity and good positive predictive values and negative predictive values. While CAT+ may be suited for patients receiving an RBC-dominant resuscitation, RI4+ is more comprehensive. RI can also be used as a continuous variable to provide quantitative as well as qualitative risk of death.Prognostic, level III.

BACKGROUND The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) study evaluated the effects of plasma and platelets on hemostasis and mortality after hemorrhage. The pulmonary consequences of resuscitation strategies that mimic whole blood, remain unknown. METHODS A secondary analysis of the PROPPR study was performed. Injured patients predicted to receive a massive transfusion were randomized to 1:1:1 versus 1:1:2 plasma-platelet-red blood cell ratios at 12 Level I North American trauma centers. Patients with survival >24 h, an intensive care unit (ICU) stay, and a recorded PaO2/FiO2 (P/F) ratio were included. Acute respiratory distress syndrome (ARDS) was defined as a P/F ratio

While transfusion-related acute lung injury (TRALI) remains the primary cause of transfusion-related fatalities (37%), recent reports estimate the incidence of TRALI at 0.008% per unit of plasma transfused and 0.004% per all products transfused. Because blood banks have moved toward male-predominant plasma, TRALI appears, anecdotally, to have been reduced to an extremely rare event. The purpose of this study was to estimate the current incidence of TRALI at a large, urban center known for its early and aggressive use of plasma in the setting of trauma, hemorrhagic shock, and massive transfusion.The Blood Bank Registry of our hospital was queried for all transfused patients admitted from September 2002 through March 2013. The blood bank collected and investigated all cases of clinical acute lung injury meeting the consensus definition for TRALI, as well as potential cases for which the donor product was recalled for having a high reactivity level of human leukocyte antigen antibodies (ie, the antibodies that could cause TRALI). Clinical reactions were reviewed in conjunction with independent serological testing and classified by transfusion medicine physicians as being "probable TRALI" or of "unrelated etiology." The total number of units transfused at our facility during this time period was also obtained, allowing the incidence of TRALI to be estimated. Cases were analyzed based on demographics, outcome, blood types, observed symptoms and their duration, and type of product transfused.Seven cases were identified at our center for the indicated time period, with only 3 of these occurring in trauma. A total of 714,757 units of blood products were transfused between September 2002 and March 2013. The incidence of TRALI was estimated to be 1 case per 100,000 units of product for the entire study period. A broad range of patients was affected. Consistent with previous descriptions, an acute duration of symptoms (average, 1.4 days) was observed and usually resolved with supportive care. Reactions were observed predominantly in plasma products, both type specific and nontype specific.This study demonstrates that while TRALI still occurs, clinically meaningful cases are rare. Moreover, TRALI rates remain low despite the increasingly aggressive use of plasma and platelets in the trauma setting.

BACKGROUND Among bleeding patients, we hypothesized that the hyperfibrinolytic (HF) phenotype would be associated with the highest mortality, whereas shutdown (SD) patients would have the greatest complication burden. METHODS Severely injured patients predicted to receive a massive transfusion at 12 Level I trauma centers were randomized to one of two transfusion ratios as described in the Pragmatic, Randomized, Optimal Platelet and Plasma Ratio trial. Fibrinolysis phenotypes were determined based on admission clot lysis at 30 minutes (LY30): SD ≤0.8%, physiologic (PHYS) 0.9-2.9%, and HF ≥3%. Univariate and multivariate analysis was performed. Logistic regression was used to adjust for age, gender, arrival physiology, shock, injury severity, center effect, and treatment arm. RESULTS Among the 680 patients randomized, 547(80%) had admission thrombelastography (TEG) values available to determine fibrinolytic phenotypes. Compared to SD and PHYS, HF patients had higher Injury Severity Score (25 vs. 25 vs. 34), greater base deficit (-8 vs. -6 vs. -12) and were more uniformly hypocoagulable on admission by PT, PTT, and TEG values; all p

Collaborative biostatistics faculties (CBF) are increasingly valued by academic health centers (AHCs) for their role in increasingsuccess rates of grants and publications, and educating medical students and clinical researchers. Some AHCs have a biostatistics department that consists of only biostatisticians focused on methodological research, collaborative research, and education. Others may have a biostatistics unit within an interdisciplinary department, or statisticians recruited into clinical departments. Within each model, there is also variability in environment, influenced by the chair’s background, research focus of colleagues, type of students taught, funding sources, and whether the department is in a medical school or school of public health. CBF appointments may be tenure track or non-tenure, and expectations for promotion may vary greatly depending on the type of department, track, and the AHC. In this article, the authors identify strategies for developing early-stage CBFs in four domains: 1)Influenceof department/environment, 2) Skills to develop, 3) Ways to increase productivity, and 4) Ways to document accomplishments. Graduating students and postdoctoral fellows should consider the first domain when choosing a faculty position. Early-stage CBFs will benefit by understanding the requirements of their environment early in their appointment and by modifying the provided progression grid with their chair and mentoring team as needed. Following this personalized grid will increase the chances of a satisfying career with appropriate recognition for academic accomplishments.

BACKGROUND Rational development of technology for rapid control of noncompressible torso hemorrhage (NCTH) requires detailed understanding of what is bleeding. Our objectives were to describe the anatomic location of truncal bleeding in patients presenting with NCTH and compare endovascular (ENDO) management versus open (OPEN) management. METHODS This is a retrospective study of adult trauma patients with NCTH admitted to four urban Level I trauma centers in the Houston and San Antonio metropolitan areas in 2008 to 2012. Inclusion criteria include named axial torso vessel disruption, Abbreviated Injury Scale chest or abdomen score of 3 or higher with shock (base excess

Background Reductions in platelet (PLT) count and function are associated with poor outcomes in trauma patients. We proposed to determine if patients expected to receive blood products have a decrease in PLT function higher than expected based on the reduction in PLT count, and if the reduction in function could be associated with the donor plasma/supernatant received. Methods PLT count and function were measured on admission to the emergency department and intensive care unit in severely injured patients expected to receive a transfusion. PLT function was measured by Multiplate aggregometry in response to five agonists. Function was corrected for alterations in count. In vitro studies were conducted in the blood of normal subjects to assess the effect of dilutions with AB donor plasma on PLT function. Results Forty-six patients were enrolled, with 87% requiring a transfusion. Median Injury Severity Score was 23 (13, 29) and mortality 15%. PLT count and function were decreased from emergency department to intensive care unit admission by 25% and 58%, respectively. Decreases in function persisted after adjustment for count. Patients requiring large volumes of blood products had reductions in function that were disproportionately greater. Reductions in PLT function were greatest after transfusion of PLTs. In in vitro studies with a 30% dilution by autologous plasma caused a relational reduction in function, whereas allogenic plasma resulted in greater decreases that were highly variable between donors. Conclusions Within hours of injury a decrease in both PLT count and function occurs, that is aggravated with the administration of blood products, with transfusion of PLTs showing the greatest effect. The effect on PLT function of allogenic transfused plasma appears to be highly donor related.

Choosing the appropriate endpoint for a trauma hemorrhage control trial can determine the likelihood of its success. Recent Phase 3 trials and observational studies have used 24-h and/or 30-day all-cause mortality as the primary endpoint and some have not used exception from informed consent (EFIC), resulting in multiple failed trials. Five recent high-quality prospective studies among 4,064 hemorrhaging trauma patients provide new evidence to support earlier primary endpoints.The goal of this project was to determine the optimal endpoint for hemorrhage control trials using existing literature and new analyses of previously published data.Recent studies among bleeding trauma patients show that hemorrhagic deaths occur rapidly, at a high rate, and in a consistent pattern. Early preventable deaths among trauma patients are largely due to hemorrhage and the median time to hemorrhagic death from admission is 2.0 to 2.6 h. Approximately 85% of hemorrhagic deaths occur within 6 h. The hourly mortality rate due to traumatic injury decreases rapidly after enrollment from 4.6% per hour at 1 hour postenrollment to 1% per hour at 6 h to 0.1% per hour by 9 h and thereafter. Early primary endpoints (within 6 h) have critically important benefits for hemorrhage control trials, including being congruent with the median time to hemorrhagic death, biologic plausibility, and enabling the use of all-cause mortality, which is definitive and objective.Primary endpoints should be congruent with the timing of the disease process. Therefore, if a resuscitation/hemorrhage control intervention is under study, a primary endpoint of all-cause mortality evaluated within the first 6 h is appropriate. Before choosing the timing of the primary endpoint for a large multicenter trial, we recommend performing a Phase 2 trial under EFIC to better understand the effects of the hemorrhage control intervention and distribution of time to death. When early primary endpoints are used, patients should be monitored for multiple subsequent secondary safety endpoints, including 24 h and 30-day all-cause mortality as well as the customary safety endpoints.

Over the last decade the age of trauma patients and injury mortality has increased. At the same time, many centers have implemented multiple interventions focused on improved hemorrhage control, effectively resulting in a bleeding control bundle of care. The objective of our study was to analyze the temporal distribution of trauma-related deaths, the factors that characterize that distribution and how those factors have changed over time at our urban level 1 trauma center.Records at an urban Level 1 trauma center were reviewed. Two time periods (2005-2006 and 2012-2013) were included in the analysis. Mortality rates were directly adjusted for age, gender and mechanism of injury. The Mann-Whitney and chi square tests were used to compare variables between periods, with significance set at 0.05.7080 patients (498 deaths) were examined in 2005-2006, while 8767 patients (531 deaths) were reviewed in 2012-2013. The median age increased 6 years, with a similar increase in those who died. In patients that died, no differences by gender, race or ethnicity were observed. Fall-related deaths are now the leading cause of death. Traumatic brain injury (TBI) and hemorrhage accounted for 91% of all deaths. TBI (61%) and multiple organ failure or sepsis (6.2%) deaths were unchanged, while deaths associated with hemorrhage decreased from 36% to 25% (p0.01). Across time periods, 26% of all deaths occurred within one hour of hospital arrival, while 59% occurred within 24h. Unadjusted mortality dropped from 7.0% to 6.1 (p=0.01) and in-hospital mortality dropped from 6.0% to 5.0% (p0.01). Adjusted mortality dropped 24% from 7.6% (95% CI: 6.9-8.2) to 5.8% (95% CI: 5.3-6.3) and in-hospital mortality decreased 30% from 6.6% (95% CI: 6.0-7.2) to 4.7 (95% CI: 4.2-5.1).Over the same time frame of this study, increases in trauma death across the globe have been reported. This single-site study demonstrated a significant reduction in mortality, attributable to decreased hemorrhagic death. It is possible that efforts focused on hemorrhage control interventions (a bleeding control bundle) resulted in this reduction. These changing factors provide guidance on future prevention and intervention efforts.

Background There have been no prior investigations of the cost effectiveness of transfusion strategies for trauma resuscitation. The Pragmatic, Randomized, Optimal Platelet and Plasma Ratios (PROPPR) study was a Phase III multisite, randomized trial in 680 subjects comparing the efficacy of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with the 1:1:2 ratio. We hypothesized that 1:1:1 transfusion results in an acceptable incremental cost-effectiveness ratio, when estimated using patients' age-specific life expectancy and cost of care during the 30-day PROPPR trial period. Study design and methods International Classification of Diseases, Ninth Revision codes were prospectively collected, and subjects were matched 1:2 to subjects in the Healthcare Utilization Program State Inpatient Data to estimate cost weights. We used a decision tree analysis, combined with standard costs and estimated years of expected survival to determine the cost effectiveness of the two treatments. Results The 1:1:1 group had higher overall costs for the blood products but were more likely to achieve hemostasis and decreased hemorrhagic death by 24 hours (p = 0.006). For every 100 patients treated in the 1:1:1 group, eight more achieved hemostasis than in the 1:1:2 group. At 30 days, the total hospital cost per 100 patients was $5.6 million in the 1:1:1 group compared with $5.0 million in the 1:1:2 group. For each 100 patients, the 1:1:1 group had 218.5 more years of life expectancy. This was at a cost of $2994 per year gained. Conclusion The 1:1:1 transfusion ratio in severely injured hemorrhaging trauma patients is a very cost-effective strategy for increasing hemostasis and decreasing trauma deaths.

Overtransfusion of packed red blood cells is known to increase the risk of death in stable patients. With the delineation of minimum transfusion ratios in hemorrhaging patients complete, attention must be turned to the other end of the massive transfusion spectrum-that of defining the maximum transfusion of packed red blood cells. We aimed to define the ideal hemoglobin range 24 hours after anatomic hemostasis associated with the lowest mortality.Massive-transfusion patients (≥10 units packed red blood cells within 24 hours) were reviewed from 2010-2013. The hemoglobin 24 ± 6 hours after anatomic hemostasis was used to stratify patients into undertransfusion (8.0 g/dL), hemoglobin transfusion target (8.0-11.9 g/dL), and overtransfusion (12.0 g/dL) groups; patients not surviving to 24 hours were excluded.We identified 418 patients (351 [84%] in the hemoglobin transfusion target group, 38 [9%] in the undertransfusion group, and 29 [7%] in the overtransfusion group) with an overall mortality of 18%. Undertransfusion patients had the greatest risk of death (odds ratio 3.3; 95% confidence interval 1.6-6.7) followed by overtransfusion patients (odds ratio 2.5; 95% confidence interval 1.1-5.6). Though pretransfusion hemoglobin was similar (9.5 ± 2.2 g/dL vs 9.5 ± 2.3 g/dL), overtransfusion patients had greater hemoglobin values during massive transfusion (8.3 ± 3.0 g/dL vs 6.9 ± 1.4 g/dL), persisting until hospital dismissal/death (11.4 ± 2.3 g/dL vs 9.6 ± 1.1 g/dL). In total, 657.4 excess packed red blood cell units were transfused (1.9 ± 1.5 per patient).Overtransfusion patients had increased mortality, comparable to undertransfusion patients, despite younger age and fewer comorbidities. Shorter massive transfusion durations foster a scenario in which patients are at greater risk of overtransfusion.

BackgroundMedication dispensing errors are common in clinical trials, and have a significant impact on the quality and validity of a trial. Therefore, the definition, calculation and evaluation of such errors are important for supporting a trial’s conclusions. A variety of medication dispensing errors can occur. In this paper, we focus on errors in trials where the intervention includes multiple therapies that must be given in a pre-specified order that varies across treatment arms and varies in duration.MethodsThe Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial was a Phase III multi-site, randomized trial to compare the effectiveness and safety of 1:1:1 transfusion ratios of plasma and platelets to red blood cells with a 1:1:2 ratio. In this trial, these three types of blood products were to be transfused in a pre-defined order that differed by treatment arm. In this paper, we present approaches from the PROPPR trial that we used to define and calculate the occurrence of out of order blood transfusion errors. We applied the proposed method to calculate protocol adherence to the specified order of transfusion in each treatment arm.ResultsUsing our proposed method, protocol adherence was greater in the 1:1:1 group than in the 1:1:2 group (96% vs 93%) (p

Background The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial has demonstrated that damage-control resuscitation, a massive transfusion strategy targeting a balanced delivery of plasma-platelet-red blood cell in a ratio of 1:1:1, results in improved survival at 3 hours and a reduction in deaths caused by exsanguination in the first 24 hours compared with a 1:1:2 ratio. In light of these findings, we hypothesized that patients receiving 1:1:1 ratio would have improved survival after emergency laparotomy. Methods Severely injured patients predicted to receive a massive transfusion admitted to 12 Level I North American trauma centers were randomized to 1:1:1 versus 1:1:2 as described in the PROPPR trial. From these patients, the subset that underwent an emergency laparotomy, defined previously in the literature as laparotomy within 90 minutes of arrival, were identified. We compared rates and timing of emergency laparotomy as well as postsurgical survival at 24 hours and 30 days. Results Of the 680 enrolled patients, 613 underwent a surgical procedure, 397 underwent a laparotomy, and 346 underwent an emergency laparotomy. The percentages of patients undergoing emergency laparotomy were 51.5% (174 of 338) and 50.3% (172 of 342) for 1:1:1 and 1:1:2, respectively (p = 0.20). Median time to laparotomy was 28 minutes in both treatment groups. Among patients undergoing an emergency laparotomy, the proportions of patients surviving to 24 hours and 30 days were similar between treatment arms; 24-hour survival was 86.8% (151 of 174) for 1:1:1 and 83.1% (143 of 172) for 1:1:2 (p = 0.29), and 30-day survival was 79.3% (138 of 174) for 1:1:1 and 75.0% (129 of 172) for 1:1:2 (p = 0.30). Conclusion We found no evidence that resuscitation strategy affects whether a patient requires an emergency laparotomy, time to laparotomy, or subsequent survival. Level of evidence Therapeutic study, level IV.

BACKGROUND Hypothermia is associated with poor outcomes after injury. The relationship between hypothermia during contemporary large volume resuscitation and blood product consumption is unknown. We evaluated this association, and the predictive value of hypothermia on mortality. METHODS Patients predicted to receive massive transfusion at 12 level 1 trauma centers were randomized in the Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial and were grouped into those who were hypothermic (

BACKGROUND Temporal changes in fibrinolytic activity after injury and their impact on outcomes remain poorly defined. We conducted a prospective, multicenter cohort study to determine the incidence of fibrinolytic phenotypes after injury and the trajectories and associated outcomes of these phenotypes over time. METHODS We included adults that arrived within 6 hours of injury to three American Level I trauma centers. Clot lysis at 30 minutes (LY-30) was measured at presentation and at 3 hours, 6 hours, 12 hours, 24 hours, 48 hours, 72 hours, 96 hours, and 120 hours. LY-30 was used to categorize patients into the following fibrinolytic phenotypes: fibrinolysis shutdown (SD, LY-30 ≤0.8%), physiologic fibrinolysis (PHYS, LY-30 >0.8% to

Endotheliopathy of trauma is characterized by breakdown of the endothelial glycocalyx. Elevated biomarkers of endotheliopathy, such as serum syndecan-1 (Synd-1) ≥ 40 ng/mL, have been associated with increased need for transfusions, complications, and mortality. We hypothesized that severely injured trauma patients who exhibit elevated Synd-1 levels shortly after admission have an increased likelihood of developing sepsis.We analyzed a subset of patients from the Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial who survived at least 72 hours after hospital admission, and we determined elevated Synd-1 levels (≥ 40 ng/mL) 4 hours after hospital arrival. Sepsis was defined a priori as meeting systemic inflammatory response criteria and having a known or suspected infection. Univariate analysis was performed to identify variables associated with elevated Synd-1 levels and sepsis. Significant variables at a value of p0.2 in the univariate analysis were chosen by purposeful selection and analyzed in a mixed effects multivariate logistic regression model to account for the 12 different study sites.We included 512 patients. Of these, 402 (79%) had elevated Synd-1 levels, and 180 (35%) developed sepsis. Median Synd-1 levels at 4 hours after admission were 70 ng/dL (interquartile range [IQR] 36 to 157 ng/dL) in patients who did not develop sepsis, and 165 ng/dL [IQR 67 to 336 ng/dL] in those who did (p0.001). Adjusting for treatment arm and site, multivariable analyses revealed that elevated Synd-1 status, Injury Severity Score (ISS), and total blood transfused were significantly associated with an increased likelihood of developing sepsis.Elevated Synd-1 levels 4 hours after admission in severely injured adult trauma patients who survived the initial 72 hours after hospital admission are associated with subsequent sepsis.

BackgroundThe ability of focused assessment with sonography for trauma (FAST) to detect clinically significant hemorrhage in hypotensive injured patients remains unclear. We sought to describe the sensitivity and specificity of FAST using findings at laparotomy as the confirmatory test.MethodsPatients from the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study that had a systolic blood pressure < 90mm Hg and underwent FAST were analysed. Results were compared with findings at laparotomy. A therapeutic laparotomy (T-LAP) was defined as an abdominal operation within 6 hours in which a definitive procedure was performed. The sensitivity and specificity of FAST were calculated.ResultsThe cohort included 317 patients that underwent FAST (108 positive, 209 negative). T-LAP was performed in 69% (n=75) of FAST(+) patients and 22% (n=48) of FAST(−) patients. FAST had a sensitivity of 62% and specificity of 83%.ConclusionsIn our multicenter cohort, 22% of FAST(−) patients underwent T-LAP within 6 hours of admission. In hypotensive patients with a negative FAST, clinicians should still maintain a high index of suspicion for significant abdominal hemorrhage.Level of evidenceLevel IV.

Most studies of trauma deaths include non-preventable deaths, potentially limiting successful intervention efforts. In this study we aimed to compare the potentially preventable trauma deaths between 2 time periods at our institution.Trauma patients who died in our hospital in 2005-2006 or 2012-2013 were included, non-preventable deaths were excluded from analysis. The Mann-Whitney and chi square test were used to compare variables between both time periods.80% of deaths were non-preventable. Between the study time periods there was a decrease in potentially preventable deaths, from 29% to 12%, p 0.001. Head injury deaths significantly decreased (40.6%-24.6%, p = 0.03), while hemorrhage deaths were stable during both time periods (47.6%-43.1%, p = 0.55).Potentially preventable trauma deaths decreased during the study period. Hemorrhage remains constant as the leading cause of potentially preventable deaths. Continued research to improve survival from hemorrhage is warranted.

Transfusing platelets during massive hemorrhage is debated because of a lack of high-quality evidence concerning outcomes in trauma patients. The objective of this study was to examine the effect of platelet transfusions on mortality in severely injured trauma patients. This work analyzed PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial patients who received only the first cooler of blood products, which either did or did not contain platelets. Primary outcomes were all-cause mortality at 24 hours and 30 days and hemostasis. Secondary outcomes included cause of death, complications, and hospital-, intensive care unit (ICU)-, and ventilator-free days. Continuous variables were compared using Wilcoxon rank sum tests. Categorical variables were compared using Fisher's exact tests. There were 261 PROPPR patients who achieved hemostasis or died before receiving a second cooler of blood products (137 received platelets and 124 did not). Patients who received platelets also received more total plasma (median, 3 vs 2 U; P < .05) by PROPPR intervention design. There were no differences in total red blood cell transfusions between groups. After controlling for plasma volume, patients who received platelets had significantly decreased 24-hour (5.8% vs 16.9%; P < .05) and 30-day mortality (9.5% vs 20.2%; P < .05). More patients in the platelet group achieved hemostasis (94.9% vs 73.4%; P < .01), and fewer died as a result of exsanguination (1.5% vs 12.9%; P < .01). Patients who received platelets had a shorter time on mechanical ventilation (P < .05); however, no differences in hospital- or ICU-free days were observed. In conclusion, early platelet administration is associated with improved hemostasis and reduced mortality in severely injured, bleeding patients. This trial was registered at www.clinicaltrials.gov as # NCT01545232.

Background Previously, a model to predict massive transfusion protocol (MTP) (activation) was derived using a single-institution data set. The PRospective, Observational, Multicenter, Major Trauma Transfusion database was used to externally validate this model's ability to predict both MTP activation and massive transfusion (MT) administration using multiple MT definitions. Methods The app model was used to calculate the predicted probability of MTP activation or MT delivery. The five definitions of MT used were: (1) 10 units packed red blood cells (PRBCs) in 24 hours, (2) Resuscitation Intensity score ≥ 4, (3) critical administration threshold, (4) 4 units PRBCs in 4 hours; and (5) 6 units PRBCs in 6 hours. Receiver operating curves were plotted to compare the predicted probability of MT with observed outcomes. Results Of 1,245 patients in the data set, 297 (24%) met definition 1, 570 (47%) met definition 2, 364 (33%) met definition 3, 599 met definition 4 (49.1%), and 395 met definition 5 (32.4%). Regardless of the outcome (MTP activation or MT administration), the predictive ability of the app model was consistent: when predicting activation of the MTP, the area under the curve for the model was 0.694 and when predicting MT administration, the area under the curve ranged from 0.695 to 0.711. Conclusion Regardless of the definition of MT used, the app model demonstrates moderate ability to predict the need for MT in an external, homogenous population. Importantly, the app allows the model to be iteratively recalibrated ("machine learning") and thus could improve its predictive capability as additional data are accrued. Level of evidence Diagnostic test study/Prognostic study, level III.

In comparative effectiveness studies of multicomponent, sequential interventions like blood product transfusion (plasma, platelets, red blood cells) for trauma and critical care patients, the timing and dynamics of treatment relative to the fragility of a patient’s condition is often overlooked and underappreciated. While many hospitals have established massive transfusion protocols to ensure that physiologically optimal combinations of blood products are rapidly available, the period of time required to achieve a specified massive transfusion standard (e.g. a 1:1 or 1:2 ratio of plasma or platelets:red blood cells) has been ignored. To account for the time-varying characteristics of transfusions, we use semiparametric rate models for multivariate recurrent events to estimate blood product ratios. We use latent variables to account for multiple sources of informative censoring (early surgical or endovascular hemorrhage control procedures or death). The major advantage is that the distributions of latent variables and the dependence structure between the multivariate recurrent events and informative censoring need not be specified. Thus, our approach is robust to complex model assumptions. We establish asymptotic properties and evaluate finite sample performance through simulations, and apply the method to data from the PRospective Observational Multicenter Major Trauma Transfusion study.

Background Positive Focused Assessment with Sonography in Trauma examination and hypotension often indicate urgent surgery. An abdomen/pelvis computed tomography (apCT) may allow less invasive management but the delay may be associated with adverse outcomes. Methods Patients in the Prospective Observational Multicenter Major Trauma Transfusion study with hypotension and a positive Focused Assessment with Sonography in Trauma (HF+) examination who underwent a CT (apCT+) were compared with those who did not. Results Of the 92 HF+ identified, 32 (35%) underwent apCT during initial evaluation and apCT was associated with decreased odds of an emergency operation (odds ratio .11, 95% confidence interval .001 to .116) and increased odds of angiographic intervention (odds ratio 14.3, 95% confidence interval 1.5 to 135). There was no significant difference in 30-day mortality or need for dialysis. Conclusions An apCT in HF+ patients is associated with reduced odds of emergency surgery, but not mortality. Select HF+ patients can safely undergo apCT to obtain clinically useful information.

BACKGROUND The Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial was a randomized clinical trial comparing survival after transfusion of two different blood component ratios for emergency resuscitation of traumatic massive hemorrhage. Transfusion services supporting the study were expected to provide thawed plasma, platelets, and red blood cells within 10 minutes of request. STUDY DESIGN AND METHODS At the 12 Level 1 trauma centers participating in PROPPR, blood components transfused and delivery times were tabulated, with a focus on universal donor (UD) plasma management. The adequacy of site plans was assessed by comparing the bedside blood availability times to study goals and the new American College of Surgeons guidelines. RESULTS Eleven of 12 sites were able to consistently deliver 6 units of thawed UD plasma to their trauma-receiving unit within 10 minutes and 12 units in 20 minutes. Three sites used blood group A plasma instead of AB for massive transfusion without complications. Approximately 4700 units of plasma were given to the 680 patients enrolled in the trial. No site experienced shortages of AB plasma that limited enrollment. Two of 12 sites reported wastage of thawed AB plasma approaching 25% of AB plasma prepared. CONCLUSION Delivering UD plasma to massively hemorrhaging patients was accomplished consistently and rapidly and without excessive wastage in high-volume trauma centers. The American College of Surgeons Trauma Quality Improvement Program guidelines for massive transfusion protocol UD plasma availability are practicable in large academic trauma centers. Use of group A plasma in trauma resuscitation needs further study.

Background Objective parameters predicting futility of care in severely injured pediatric patients are lacking. Although futility of care has been investigated in a limited number of studies in trauma patients, none of these studies achieves a 100% success rate in a large cohort of pediatric patients. The purpose of the current study was to identify extreme laboratory values that could be used to predict 100% mortality in severely injured children. Study Design We evaluated a registry-based, historical cohort of all severely injured children (Level I trauma, younger than 16 years old) who were not dead on arrival between January 2010 and December 2016 from a single Level I trauma center. Extreme arrival laboratory data were evaluated both alone and in conjunction with traumatic brain injury. Results There were 1,292 patients who met inclusion criteria, of which 1,169 (90.5%) survived and 123 (9.5%) died. Those who died were significantly younger, with higher head Abbreviated Injury Scale scores and overall Injury Severity Scores. Single extreme laboratory values were identified that predicted mortality perfectly (100% positive predictive value): international normalized ratio ≥3.0, pH ≤6.95, base excess ≤ -22, platelet count ≤30,000, hemoglobin ≤5.0 g/dL, rapid thromboelastography ≤30 mm, and rapid thromboelastography lysis at 30 minutes ≥50%. When 2 laboratory values or the presence of traumatic brain injury were added, lower thresholds for futility were noted. Conclusions Extreme admission laboratory values are capable of predicting 100% mortality and futility of additional care in severely injured children with a high level of accuracy. Validation of these single-center findings is warranted and, if supported, should initiate a discussion within the pediatric trauma community about application and cessation of resuscitation efforts to optimize resource use.

Background Often the clinician is faced with a diagnostic and therapeutic dilemma in patients with concomitant traumatic brain injury (TBI) and hemorrhagic shock (HS), as rapid deterioration from either can be fatal. Knowledge about outcomes after concomitant TBI and HS may help prioritize the emergent management of these patients. We hypothesized that patients with concomitant TBI and HS (TBI + HS) had worse outcomes and required more intensive care compared with patients with only one of these injuries. Methods This is a post hoc analysis of the Pragmatic, Randomized Optimal Platelets and Plasma Ratios (PROPPR) trial. TBI was defined by a head Abbreviated Injury Scale score greater than 2. HS was defined as a base excess of -4 or less and/or shock index of 0.9 or greater. The primary outcome for this analysis was mortality at 30 days. Logistic regression, using generalized estimating equations, was used to model categorical outcomes. Results Six hundred seventy patients were included. Patients with TBI + HS had significantly higher lactate (median, 6.3; interquartile range, 4.7-9.2) compared with the TBI group (median, 3.3; interquartile range, 2.3-4). TBI + HS patients had higher activated prothrombin times and lower platelet counts. Unadjusted mortality was higher in the TBI + HS (51.6%) and TBI (50%) groups compared with the HS (17.5%) and neither group (7.7%). Adjusted odds of death in the TBI and TBI + HS groups were 8.2 (95% confidence interval, 3.4-19.5) and 10.6 (95% confidence interval, 4.8-23.2) times higher, respectively. Ventilator, intensive care unit-free and hospital-free days were lower in the TBI and TBI + HS groups compared with the other groups. Patients with TBI + HS or TBI had significantly greater odds of developing a respiratory complication compared with the neither group. Conclusion The addition of TBI to HS is associated with worse coagulopathy before resuscitation and increased mortality. When controlling for multiple known confounders, the diagnosis of TBI alone or TBI+HS was associated with significantly greater odds of developing respiratory complications. Level of evidence Prognostic study, level II.

American College of Surgeons Trauma Quality Improvement Best Practices recommends initial massive transfusion (MT) cooler delivery within 15 minutes of protocol activation, with a goal of 10 minutes. The current study sought to examine the impact of timing of first cooler delivery on patient outcomes.Patients predicted to receive MT at 12 Level I trauma centers were randomized to two separate transfusion ratios as described in the PROPPR trial. Assessment of Blood Consumption score or clinician gestalt prediction of MT was used to randomize patients and call for initial study cooler. In this planned subanalysis, the time to MT protocol activation and time to delivery of the initial cooler were evaluated. The impact of these times on mortality and time to hemostasis were examined using both Wilcoxon rank sum and linear and logistic regression.Among 680 patients, the median time from patient arrival to MT protocol activation was 9 minutes with a median time from MT activation call to delivery of first cooler of 8 minutes. An increase in both time to MT activation and time to arrival of first cooler were associated with prolonged time to achieving hemostasis (coefficient, 1.09; p = 0.001 and coefficient, 1.16; p0.001, respectively). Increased time to MT activation and time to arrival of first cooler were associated with increased mortality (odds ratio [OR], 1.02; p = 0.009 and OR, 1.02; p = 0.012, respectively). Controlling for injury severity, physiology, resuscitation intensity, and treatment arm (1:1:1 vs. 1:1:2), increased time to arrival of first cooler was associated with an increased mortality at 24 hours (OR, 1.05; p = 0.035) and 30 days (OR, 1.05, p = 0.016).Delays in MT protocol activation and delays in initial cooler arrival were associated with prolonged time to achieve hemostasis and an increase in mortality. Independent of products ratios, every minute from time of MT protocol activation to time of initial cooler arrival increases odds of mortality by 5%.Prognostic, level II; Therapeutic, level III.