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Posttraumatic venous thromboembolism (VTE) remains prevalent in severely injured patients despite chemoprophylaxis. Importantly, although platelets are central to thrombosis, they are not routinely targeted in prevention of posttraumatic VTE. Furthermore, platelets from injured patients show ex vivo evidence of increased activation yet impaired aggregation, consistent with functional exhaustion. However, the relationship of this platelet functional phenotype with development of posttraumatic VTE is unknown. We hypothesized that, following injury, impaired ex vivo platelet aggregation (PA) is associated with the development of posttraumatic VTE.We performed a secondary analysis of 133 severely injured patients from a prospective observational study investigating coagulation and inflammation (2011-2019). Platelet aggregation in response to stimulation with adenosine diphosphate (ADP), collagen, and thrombin was measured at presentation (preresuscitation) and 24 hours (postresuscitation). Viscoelastic clot strength and lysis were measured in parallel by thromboelastography. Multivariable regression examined relationships between PA at presentation, 24 hours, and the change (δ) in PA between presentation and 24 hours with development of VTE.The 133 patients were severely injured (median Injury Severity Score, 25), and 14% developed VTE (all48 hours after admission). At presentation, platelet count and PA were not significantly different between those with and without incident VTE. However, at 24 hours, those who subsequently developed VTE had significantly lower platelet counts (126 × 10 9 /L vs. 164 × 10 9 /L, p = 0.01) and lower PA in response to ADP ( p0.05), collagen ( p0.05), and thrombin ( p = 0.06). Importantly, the magnitude of decrease in PA (δ) from presentation to 24 hours was independently associated with development of VTE (adjusted odds ratios per 10 aggregation unit decrease: δ-ADP, 1.31 [ p = 0.03]; δ-collagen, 1.36 [ p = 0.01]; δ-thrombin, 1.41 [ p0.01]).Severely injured patients with decreasing ex vivo measures of PA despite resuscitation have an increased risk of developing VTE. This may have implications for predicting development of VTE and for studying platelet targeted chemoprophylaxis regimens.Prognostic/Epidemiological; Level III.

Proposed mechanisms of acute traumatic coagulopathy (ATC) include decreased clotting potential due to factor consumption and proteolytic inactivation of factor V (FV) and activated factor V (FVa) by activated protein C (aPC). The role of FV/FVa depletion or inactivation in burn-induced coagulopathy is not well characterized. This study evaluates FV dynamics following burn and nonburn trauma.Burn and trauma patients were prospectively enrolled. Western blotting was performed on admission plasma to quantitate levels of FV antigen and to assess for aPC or other proteolytically derived FV/FVa degradation products. Statistical analysis was performed with Spearman's, Chi-square, Mann-Whitney U test, and logistic regression.Burn (n = 60) and trauma (n = 136) cohorts showed similar degrees of FV consumption with median FV levels of 76% versus 73% (P = 0.65) of normal, respectively. Percent total body surface area (TBSA) was not correlated with FV, nor were significant differences in median FV levels observed between low and high TBSA groups. The injury severity score (ISS) in trauma patients was inversely correlated with FV (ρ = -0.26; P = 0.01) and ISS ≥ 25 was associated with a lower FV antigen level (64% versus. 93%; P = 0.009). The proportion of samples showing proteolysis-derived FV was greater in trauma than burn patients (42% versus. 16%; P = 0.0006).Increasing traumatic injury severity is associated with decreased FV antigen levels, and a greater proportion of trauma patient samples exhibit proteolytically degraded FV fragments. These associations are not present in burns, suggesting that mechanisms underlying FV depletion in burn and nonburn trauma are not identical.

BACKGROUND Despite the widespread institution of modern massive transfusion protocols with balanced blood product ratios, survival for patients with traumatic hemorrhage receiving ultramassive transfusion (UMT) (defined as ≥20 U of packed red blood cells [RBCs]) in 24 hours) remains low and resource consumption remains high. Therefore, we aimed to identify factors associated with mortality in trauma patients receiving UMT in the modern resuscitation era. METHODS An Eastern Association for the Surgery of Trauma multicenter retrospective study of 461 trauma patients from 17 trauma centers who received ≥20 U of RBCs in 24 hours was performed (2014-2019). Multivariable logistic regression and Classification and Regression Tree analysis were used to identify clinical characteristics associated with mortality. RESULTS The 461 patients were young (median age, 35 years), male (82%), severely injured (median Injury Severity Score, 33), in shock (median shock index, 1.2; base excess, -9), and transfused a median of 29 U of RBCs, 22 U of fresh frozen plasma (FFP), and 24 U of platelets (PLT). Mortality was 46% at 24 hours and 65% at discharge. Transfusion of RBC/FFP ≥1.5:1 or RBC/PLT ≥1.5:1 was significantly associated with mortality, most pronounced for the 18% of patients who received both RBC/PLT and RBC/FFP ≥1.5:1 (odds ratios, 3.11 and 2.81 for mortality at 24 hours and discharge; both p < 0.01). Classification and Regression Tree identified that age older than 50 years, low initial Glasgow Coma Scale, thrombocytopenia, and resuscitative thoracotomy were associated with low likelihood of survival (14-26%), while absence of these factors was associated with the highest survival (71%). CONCLUSION Despite modern massive transfusion protocols, one half of trauma patients receiving UMT are transfused with either RBC/FFP or RBC/PLT in unbalanced ratios ≥1.5:1, with increased associated mortality. Maintaining focus on balanced ratios during UMT is critical, and consideration of advanced age, poor initial mental status, thrombocytopenia, and resuscitative thoracotomy can aid in prognostication. LEVEL OF EVIDENCE Prognostic, level III.

Background Platelet behavior in trauma-induced coagulopathy is poorly understood. Injured patients have impaired platelet aggregation (dysfunction) in ex vivo agonist-stimulated platelet aggregometry (PA). However, PA assumes that platelets are inactivated before ex vivo stimulated aggregation, which may be altered by injury. We hypothesized that following trauma, platelet aggregation (area under the curve) is decreased regardless of injury burden, but that (1) minor injury is associated with an increased baseline electrical impedance, characteristic of a functional platelet phenotype (platelets that activate in response to injury), and that (2) severe injury is not associated with an increased baseline electrical impedance, characteristic of a dysfunctional phenotype (platelets that do not activate well in response to injury) compared with healthy controls. Methods Blood from 458 trauma patients and 30 healthy donors was collected for PA. Baseline electrical impedance (Ω); platelet aggregation stimulated by adenosine diphosphate, collagen, thrombin, and arachidonic acid; and rotational thromboelastometry were measured. Multivariate regression was performed to identify associations of PA measures with blood transfusion. Results Compared with healthy controls, injured patients had impaired platelet aggregation in response to ex vivo stimulation, regardless of injury burden. However, minorly injured patients had increased endogenous platelet activation (baseline electrical impedance, Ω: with shock, p = 0.012; without shock, p = 0.084), but severely injured patients did not have significant increases in endogenous platelet activation (baseline electrical impedance, Ω: with shock, p = 0.86; without shock, p = 0.37). For every 10 Ω increase in baseline electrical impedance, there was an 8% decrease in units of blood transfused in the first 24 h (-0.08; confidence interval, -0.14 to -0.02; p = 0.015). Conclusion Injury and shock confer differential patterns of platelet aggregation in PA. Minor injury overestimates the presence of platelet dysfunction, while severe injury induces a truly dysfunctional phenotype-platelets that do not activate nor aggregate appropriately after injury. This is consequential in improving accurate phenotyping of postinjury platelet behavior for platelet-based therapeutics. Level of evidence Prognostic, level IV.

Care teams on complex surgical services face a growing list of competing expectations. Approaches to quality improvement must use minimal resources and address both system and human requirements to meet expectations without compromising care. The purpose of this study was to demonstrate that iterative prototyping, combined with a rigorous quantitative evaluation approach, can effectively improve system and stakeholder efficiency on daily trauma surgical rounds at an academic safety-net hospital and level 1 trauma center.This study occurred between May 2017 and October 2017 at the Zuckerberg San Francisco General Hospital and Trauma Center. Care team members rounding on the trauma service included attending trauma surgeons, fellows, residents, interns, nurse practitioners, pharmacists, and medical students. We used human-centered design to develop and test solutions to improve the surgical rounding process. Each prototype was evaluated using qualitative design research methods, which informed the next iteration. Time observations of rounding activities were adopted from the Lean methodology and tracked before and after implementation. Intern work hours, on-time operative starts, and discharge order times were also tracked before and after implementation.Four prototypes were designed and iteratively implemented, producing care team satisfaction by the end of the implementation period. Discharge order times decreased by a median of 58 min, intern work hours were decreased by 97 min/d, and first operative case on-time starts increased from 40% to 63% (P 0.05). The time spent on clarifications decreased by 4.7% (P 0.05), allowing for more time to discuss care plans with the patients themselves.Iterative prototyping as part of a human-centered design methodology is a powerful tool to address complex systems with diverse interests and competing priorities. Rapid, in-context prototyping is feasible on a complex trauma surgical service and can result in improved workflows and efficiency for the system and its stakeholders.

This study aimed to characterize changes in firearm injuries at 5 level 1 trauma centers in Northern California in the 12 months following the start of the COVID-19 pandemic compared with the preceding 4 years, accounting for regional variations and seasonal trends.Increased firearm injuries have been reported during the early peaks of the COVID-19 pandemic despite shelter-in-place restrictions. However, these data are overwhelmingly from singlecenter studies, during the initial phase of the pandemic prior to lifting of shelter-in-place restrictions, or do not account for seasonal trends.An interrupted time-series analysis (ITSA) of all firearm injuries presenting to 5 adult level 1 trauma centers in Northern California was performed (January 2016to February 2021). ITSA modeled the association of the onset of the COVID-19 pandemic (March 2020) with monthly firearm injuries using the ordinary least-squares method, included month indicators to adjust for seasonality, and specified lags of up to 12 months to account for autocorrelation.Prior to the start of COVID-19, firearm injuries averaged (±SD) of 86 (±16) and were decreasing by 0.5/month (P0.01). The start of COVID- 19 (March 2020) was associated with an alarming increase of 39 firearm injuries/month (P0.01) followed by an ongoing rise of 3.5/mo (P0.01). This resulted in an average of 130 (±26) firearm injuries/month during the COVID-19 period and included 8 of the 10 highest monthly firearm injury rates in the past 5 years.These data highlight an alarming escalation in firearm injuries in the 12 months following the onset of the COVID-19 pandemic in Northern California. Additional studies and resources are needed to better understand and address this parallel public health crisis.

Supplemental digital content is available in the text., BACKGROUND The earliest measurable changes to postinjury platelet biology may be in the platelet transcriptome, as platelets are known to carry messenger ribonucleic acids (RNAs), and there is evidence in other inflammatory and infectious disease states of differential and alternative platelet RNA splicing in response to changing physiology. Thus, the aim of this exploratory pilot study was to examine the platelet transcriptome and platelet RNA splicing signatures in trauma patients compared with healthy donors. METHODS Preresuscitation platelets purified from trauma patients (n = 9) and healthy donors (n = 5) were assayed using deep RNA sequencing. Differential gene expression analysis, weighted gene coexpression network analysis, and differential alternative splicing analyses were performed. In parallel samples, platelet function was measured with platelet aggregometry, and clot formation was measured with thromboelastography. RESULTS Differential gene expression analysis identified 49 platelet RNAs to have differing abundance between trauma patients and healthy donors. Weighted gene coexpression network analysis identified coexpressed platelet RNAs that correlated with platelet aggregation. Differential alternative splicing analyses revealed 1,188 splicing events across 462 platelet RNAs that were highly statistically significant (false discovery rate

Prehospital identification of the injured patient likely to require emergent care remains a challenge. End-tidal carbon dioxide (ETCO2) has been used in the prehospital setting to monitor respiratory physiology and confirmation of endotracheal tube placement. Low levels of ETCO2 have been demonstrated to correlate with injury severity and mortality in a number of in-hospital studies. We hypothesized that prehospital ETCO2 values would be predictive of mortality and need for massive transfusion (MT) in intubated patients.This was a retrospective multicenter trial with 24 participating centers. Prehospital, emergency department, and hospital values were collected. Receiver operating characteristic curves were created and compared. Massive transfusion defined as10 U of blood in 6 hours or death in 6 hours with at least 1 U of blood transfused.A total of 1,324 patients were enrolled. ETCO2 (area under the receiver operating characteristic curve [AUROC], 0.67; confidence interval [CI], 0.63-0.71) was better in predicting mortality than shock index (SI) (AUROC, 0.55; CI, 0.50-0.60) and systolic blood pressure (SBP) (AUROC, 0.58; CI, 0.53-0.62) (p0.0005). Prehospital lowest ETCO2 (AUROC, 0.69; CI, 0.64-0.75), SBP (AUROC, 0.75; CI, 0.70-0.81), and SI (AUROC, 0.74; CI, 0.68-0.79) were all predictive of MT. Analysis of patients with normotension demonstrated lowest prehospital ETCO2 (AUROC, 0.66; CI, 0.61-0.71), which was more predictive of mortality than SBP (AUROC, 0.52; CI, 0.47-0.58) or SI (AUROC, 0.56; CI, 0.50-0.62) (p0.001). Lowest prehospital ETCO2 (AUROC, 0.75; CI, 0.65-0.84), SBP (AUROC, 0.63; CI, 0.54-0.74), and SI (AUROC, 0.64; CI, 0.54-0.75) were predictive of MT in normotensive patients. ETCO2 cutoff for MT was 26 mm Hg. The positive predictive value was 16.1%, and negative predictive value was high at 98.1%.Prehospital ETCO2 is predictive of mortality and MT. ETCO2 outperformed traditional measures such as SBP and SI in the prediction of mortality. ETCO2 may outperform traditional measures in predicting need for transfusion in occult shock.Diagnostic test, level III.

Supplemental digital content is available in the text., BACKGROUND Trauma-induced coagulopathy is a major driver of mortality following severe injury. Viscoelastic goal-directed resuscitation can reduce mortality after injury. The TEG 5000 system is widely used for viscoelastic testing. However, the TEG 6s system incorporates newer technology, with encouraging results in cardiovascular interventions. The purpose of this study was to validate the TEG 6s system for use in trauma patients. METHODS Multicenter noninvasive observational study for method comparison conducted at 12 US Levels I and II trauma centers. Agreement between the TEG 6s and TEG 5000 systems was examined using citrated kaolin reaction time (CK.R), citrated functional fibrinogen maximum amplitude (CFF.MA), citrated kaolin percent clot lysis at 30 minutes (CK.LY30), citrated RapidTEG maximum amplitude (CRT.MA), and citrated kaolin maximum amplitude (CK.MA) parameters in adults meeting full or limited trauma team criteria. Blood was drawn ≤1 hour after admission. Assays were repeated in duplicate. Reliability (TEG 5000 vs. TEG 6s analyzers) and repeatability (interdevice comparison) was quantified. Linear regression was used to define the relationship between TEG 6s and TEG 5000 devices. RESULTS A total of 475 patients were enrolled. The cohort was predominantly male (68.6%) with a median age of 49 years. Regression line slope estimates (ß) and linear correlation estimates (p) were as follows: CK.R (ß = 1.05, ρ = 0.9), CFF.MA (ß = 0.99, ρ = 0.95), CK.LY30 (ß = 1.01, ρ = 0.91), CRT.MA (TEG 6s) versus CK.MA (TEG 5000) (ß = 1.06, ρ = 0.86) as well as versus CRT.MA (TEG 5000) (ß = 0.93, ρ = 0.93), indicating strong reliability between the devices. Overall, within-device repeatability was better for TEG 6s versus TEG 5000, particularly for CFF.MA and CK.LY30. CONCLUSION The TEG 6s device appears to be highly reliable for use in trauma patients, with close correlation to the TEG 5000 device and equivalent/improved within-device reliability. Given the potential advantages of using the TEG 6s device at the site of care, confirmation of agreement between the devices represents an important advance in diagnostic testing. LEVEL OF EVIDENCE Diagnostic test, level II.

Background End-tidal carbon dioxide (ETCO2) is routinely used during elective surgery to monitor ventilation. The role of ETCO2 monitoring in emergent trauma operations is poorly understood. We hypothesized that ETCO2 values underestimate plasma carbon dioxide (pCO2) values during resuscitation for hemorrhagic shock. Methods Multicenter trial was performed analyzing the correlation between ETCO2 and pCO2 levels. Results Two hundred fifty-six patients resulted in 587 matched pairs of ETCO2 and pCO2. Correlation between these two values was very poor with an R of 0.04. 40.2% of patients presented to the operating room acidotic and hypercarbic with a pH less than 7.30 and a pCO2 greater than 45 mm Hg. Correlation was worse in patients that were either acidotic or hypercarbic. Forty-five percent of patients have a difference greater than 10 mm Hg between ETCO2 and pCO2. A pH less than 7.30 was predictive of an ETCO2 to pCO2 difference greater than 10 mm Hg. A difference greater than 10 mm Hg was predictive of mortality independent of confounders. Conclusion Nearly one half (45%) of patients were found to have an ETCO2 level greater than 10 mm Hg discordant from their PCO2 level. Reliance on the discordant values may have contributed to the 40% of patients in the operating room that were both acidotic and hypercarbic. Early blood gas analysis is warranted, and a lower early goal of ETCO2 should be considered. Level of evidence Therapeutic, level IV.

BackgroundTrauma-induced coagulopathy can present as abnormalities in a conventional or viscoelastic coagulation assay or both. We hypothesized that patients with discordant coagulopathies reflect different clinical phenotypes.MethodsBlood samples were collected prospectively from critically injured patients upon arrival at two urban Level I trauma centers. International normalized ratio (INR), partial thromboplastin time (PTT), thromboelastography (TEG), and coagulation factors were assayed.Results278 patients (median ISS 17, mortality 26%) were coagulopathic: 20% with isolated abnormal INR and/or PTT (CONVENTIONAL), 49% with isolated abnormal TEG (VISCOELASTIC), and 31% with abnormal INR/PTT and TEG (BOTH). Compared with VISCOELASTIC, CONVENTIONAL and BOTH had higher ISS, lower GCS, larger base deficit, and decreased factor activities (all p

BackgroundAcute respiratory distress syndrome (ARDS) following trauma is historically associated with crystalloid and blood product exposure. Advances in resuscitation have occurred over the last decade, but their impact on ARDS is unknown. We sought to investigate predictors of postinjury ARDS in the era of hemostatic resuscitation.MethodsData were prospectively collected from arrival to 28 days for 914 highest-level trauma activations who required intubation and survived more than 6 hours from 2005 to 2016 at a Level I trauma center. Patients with ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 mmHg or less during the first 8 days were identified. Two blinded expert clinicians adjudicated all chest radiographs for bilateral infiltrates in the first 8 days. Those with left-sided heart failure detected were excluded. Multivariate logistic regression was used to define predictors of ARDS.ResultsOf the 914 intubated patients, 63% had a ratio of partial pressure of oxygen to fraction of inspired oxygen of 300 or less, and 22% developed ARDS; among the ARDS cases, 57% were diagnosed early (in the first 24 hours), and 43% later. Patients with ARDS diagnosed later were more severely injured (ISS 32 vs. 20, p = 0.001), with higher rates of blunt injury (84% vs. 72%, p = 0.008), chest injury (58% vs. 36%, p < 0.001), and traumatic brain injury (72% vs. 48%, p < 0.001) compared with the no ARDS group. In multivariate analysis, head/chest Abbreviated Injury Score scores, crystalloid from 0 to 6 hours, and platelet transfusion from 0 to 6 hours and 7 to 24 hours were independent predictors of ARDS developing after 24 hours.ConclusionsBlood and plasma transfusion were not independently associated with ARDS. However, platelet transfusion was a significant independent risk factor. The role of platelets warrants further investigation but may be mechanistically explained by lung injury models of pulmonary platelet sequestration with peripheral thrombocytopenia.Level of evidencePrognostic study, level IV.

Objective We aimed to examine biomarkers for screening unhealthy alcohol use in the trauma setting. Summary and background data Self-report tools are the practice standard for screening unhealthy alcohol use; however, their collection suffers from recall bias and incomplete collection by staff. Methods We performed a multi-center prospective clinical study of 251 adult patients who arrived within 24 hours of injury with external validation in another 60 patients. The Alcohol Use Disorders Identification Test served as the reference standard. The following biomarkers were measured: (1) phosphatidylethanol (PEth); (2) ethyl glucuronide; (3) ethyl sulfate; (4) gamma-glutamyl-transpeptidase; (5) carbohydrate deficient transferrin; and (6) blood alcohol concentration (BAC). Candidate single biomarkers and multivariable models were compared by considering discrimination (AUROC). The optimal cutpoint for the final model was identified using a criterion for setting the minimum value for specificity at 80% and maximizing sensitivity. Decision curve analysis was applied to compare to existing screening with BAC. Results PEth alone had an AUROC of 0.93 (95% CI: 0.92-0.93) in internal validation with an optimal cutpoint of 25 ng/mL. A 4-variable biomarker model as well as the addition of any single biomarker to PEth did not improve AUROC over PEth alone (p > 0.05). Decision curve analysis showed better performance of PEth over BAC across most predicted probability thresholds. In external validation, sensitivity and specificity were 76.0% (95% CI: 53.0%-92.0%) and 73.0% (95% CI: 56.0%-86.0%), respectively. Conclusion and relevance PEth alone proved to be the single best biomarker for screening of unhealthy alcohol use and performed better than existing screening systems with BAC. PEth may overcome existing screening barriers.

BackgroundMobilization of intra and extracellular calcium is required for platelet activation, aggregation, and degranulation. However, the importance of alterations in the calcium-platelet axis after injury is unknown. We hypothesized that in injured patients, in vivo initial calcium concentrations (pretransfusion) predict ex vivo platelet activation and aggregation, viscoelastic clot strength, and transfusion of blood products. We additionally hypothesized that increasing calcium concentrations ex vivo increases the expression of platelet activation surface receptors and platelet aggregation responses to agonist stimulation in healthy donor blood.MethodsBlood samples were collected from 538 trauma patients on arrival to the emergency department. Standard assays (including calcium), platelet aggregometry (PA) and thromboelastometry (ROTEM) were performed. In PA, platelet activation (prestimulation impedance [Ω]) and aggregation responses to agonist stimulation (area under the aggregation curve [AUC]) with adenosine diphosphate (ADP), thrombin receptor-activating peptide, arachidonic acid (AA), and collagen (COL) were measured. Multivariable regression tested the associations of calcium with PA, ROTEM, and transfusions. To further examine the calcium-platelet axis, calcium was titrated in healthy blood. Platelet aggregometry and ROTEM were performed, and expression of platelet glycoprotein IIb/IIIa and P-selectin was measured by flow cytometry.ResultsThe patients were moderately injured with normal calcium and platelet counts. Higher calcium on arrival (pretransfusion) was independently associated with increased platelet activation (prestimulation, Ω; p < 0.001), aggregation (ADP-stimulated, AUC; p = 0.002; thrombin receptor-activating peptide-stimulated, AUC; p = 0.038), and clot strength (ROTEM max clot firmness; p < 0.001), and inversely associated with 24-hour transfusions of blood, plasma, and platelets (all p < 0.005). Up-titrating calcium in healthy blood increased platelet activation (prestimulation, Ω; p < 0.001), aggregation (ADP, AA, COL-stimulated AUCs; p < 0.050), and expression of P-selectin (p = 0.003).ConclusionInitial calcium concentrations (pretransfusion) are independently associated with platelet activation, aggregation, clot-strength, and transfusions after injury. These changes may be mediated by calcium driven expression of surface receptors necessary for platelet activation and aggregation. However, the therapeutic benefit of early, empiric calcium repletion in trauma patients remains undefined.Level of evidencePrognostic, level V.

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.

IntroductionWomen are under-represented in the surgical disciplines and gender bias is believed to play a factor. We aimed to understand the gender distribution of membership, leadership opportunities, and scientific contributions to annual trauma professional meetings as a case study of gender issues in trauma surgery.MethodsRetrospective collection of membership, leadership, presentation and publication data from 2016 to 2018 Trauma/Acute Care Surgery/Surgical Critical Care (TACSCC) Annual Meetings. Gender was assigned based on self-identification in demographic information, established relationships, or public sources.ResultsWomen remain under-represented with only 28.1% of those ascertaining American Board of Surgery certification in critical care self-identifying as female. The proportion of female members in Eastern Association for the Surgery of Trauma (EAST) was comparable (29.4%), slightly lower for Western Trauma Association (WTA) (19.0%), and lowest for American Association for the Surgery of Trauma (AAST) (12.8%, pConclusionFewer women than men pursue careers in the trauma field. Continuing to provide mentorship, leadership, and scientific recognition will increase gender diversity in TACSCC. We must continue to promote, sponsor, recognize, invite, and elect ‘her’.Level of evidenceIII, Epidemiology.

Screening for blunt cerebrovascular injuries (BCVIs) in asymptomatic high-risk patients has become routine. To date, the length of this asymptomatic period has not been defined. Determining the time to stroke could impact therapy including earlier initiation of antithrombotics in multiply injured patients. The purpose of this study was to determine the time to stroke in patients with a BCVI-related stroke. We hypothesized that the majority of patients suffer stroke between 24 hours and 72 hours after injury.Patients with a BCVI-related stroke from January 2007 to January 2017 from 37 trauma centers were reviewed.During the 10-year study, 492 patients had a BCVI-related stroke; the majority were men (61%), with a median age of 39 years and ISS of 29. Stroke was present at admission in 182 patients (37%) and occurred during an Interventional Radiology procedure in six patients. In the remaining 304 patients, stroke was identified a median of 48 hours after admission: 53 hours in the 144 patients identified by neurologic symptoms and 42 hours in the 160 patients without a neurologic examination and an incidental stroke identified on imaging. Of those patients with neurologic symptoms, 88 (61%) had a stroke within 72 hours, whereas 56 had a stroke after 72 hours; there was a sequential decline in stroke occurrence over the first week. Of the 304 patients who had a stroke after admission, 64 patients (22%) were being treated with antithrombotics when the stroke occurred.The majority of patients suffer BCVI-related stroke in the first 72 hours after injury. Time to stroke can help inform clinicians about initiation of treatment in the multiply injured patient.Prognostic/Epidemiologic, level III.

Background Mortality prediction aids clinical decision making and is necessary for quality improvement initiatives. Validated metrics rely on prespecified variables and often require advanced diagnostics, which are unfeasible in resource-constrained contexts. We hypothesize that machine learning will generate superior mortality prediction in both high-income and low- and middle-income country cohorts. Methods SuperLearner, an ensemble machine-learning algorithm, was applied to data from three prospective trauma cohorts: a highest-activation cohort in the United States, a high-volume center cohort in South Africa (SA), and a multicenter registry in Cameroon. Cross-validation was used to assess model discrimination of discharge mortality by site using receiver operating characteristic curves. SuperLearner discrimination was compared with standard scoring methods. Clinical variables driving SuperLearner prediction at each site were evaluated. Results Data from 28,212 injured patients were used to generate prediction. Discharge mortality was 17%, 1.3%, and 1.7% among US, SA, and Cameroonian cohorts. SuperLearner delivered superior prediction of discharge mortality in the United States (area under the curve [AUC], 94-97%) and vastly superior prediction in Cameroon (AUC, 90-94%) compared with conventional scoring algorithms. It provided similar prediction to standard scores in the SA cohort (AUC, 90-95%). Context-specific variables (partial thromboplastin time in the United States and hospital distance in Cameroon) were prime drivers of predicted mortality in their respective cohorts, whereas severe brain injury predicted mortality across sites. Conclusions Machine learning provides excellent discrimination of injury mortality in diverse settings. Unlike traditional scores, data-adaptive methods are well suited to optimizing precise site-specific prediction regardless of diagnostic capabilities or data set inclusion allowing for individualized decision making and expanded access to quality improvement programming. Level of evidence Prognostic and therapeutic, level II and III.

Goal-directed hemostatic resuscitation based on thrombelastography (TEG) has a survival benefit compared with conventional coagulation assays such as international normalized ratio, activated partial thromboplastin time, fibrinogen level, and platelet count. While TEG-based transfusion thresholds for patients at risk for massive transfusion (MT) have been defined using rapid TEG, cutoffs have not been defined for TEG using other activators such as kaolin. The purpose of this study was to develop thresholds for blood product transfusion using citrated kaolin TEG (CK-TEG) in patients at risk for MT.CK-TEG was assessed in trauma activation patients at two Level 1 trauma centers admitted between 2010 and 2017. Receiver operating characteristic (ROC) curve analyses were performed to test the predictive performance of CK-TEG measurements in patients requiring MT, defined as10 units of red blood cells or death within the first 6 hours. The Youden Index defined optimal thresholds for CK-TEG-based resuscitation.Of the 825 trauma activations, 671 (81.3%) were men, 419 (50.8%) suffered a blunt injury, and 62 (7.5%) received a MT. Patients who had a MT were more severely injured, had signs of more pronounced shock, and more abnormal coagulation assays. CK-TEG R-time was longer (4.9 vs. 4.4 min, p = 0.0084), angle was lower (66.2 vs. 70.3 degrees, p0.0001), maximum amplitude was lower in MT (57 vs. 65.5 mm, p0.0001), and LY30 was greater (1.8% vs. 1.2%, p = 0.0012) in patients with MT compared with non-MT. To predict MT, R-time yielded an area under the ROC curve (AUROC) = 0.6002 and a cut point of4.45 min. Angle had an AUROC = 0.6931 and a cut point of67 degrees. CMA had an AUROC = 0.7425, and a cut point of60 mm. LY30 had an AUROC = 0.623 with a cut point of4.55%.We have identified CK-TEG thresholds that can guide MT in trauma. We propose plasma transfusion for R-time4.45 min, fibrinogen products for an angle67 degrees, platelet transfusion for MA60 mm, and antifibrinolytics for LY304.55%.Therapeutic study, level V.

Background Posttraumatic acute respiratory distress syndrome (ARDS) is associated with prolonged mechanical ventilation and longer hospitalizations. The relationship between posttraumatic ARDS severity and financial burden has not been previously studied. We hypothesized that increasing ARDS severity is associated with incrementally higher health care costs. Methods Adults arriving as the highest level of trauma activation were enrolled in an ongoing prospective cohort study. Patients who survived 6 hours or longer are included in the analysis. Blinded review of chest radiographs was performed by two independent physicians for any intubated patient with PaO2:FIO2 ratio of 300 mmHg or lower during the first 8 days of admission. The severity of ARDS was classified by the Berlin criteria. Hospital charge data were used to perform standard costing analysis. Results Acute respiratory distress syndrome occurred in 13% (203 of 1,586). The distribution of disease severity was 33% mild, 42% moderate, and 25% severe. Patients with ARDS were older (41 years vs. 35 years, p Conclusion The development of posttraumatic ARDS is associated with higher health care costs. Among trauma patients who develop ARDS, total hospital charges per day increase with worsening severity of disease. Prevention, early recognition, and treatment of ARDS after trauma are potentially important objectives for efforts to control health care costs in this population. Level of evidence Economic and value-based evaluations, level IV.

BACKGROUND:Alcohol has been associated with altered viscoelastic testing in trauma, indicative of impaired coagulation. Such alterations, however, show no correlation to coagulopathy-related outcomes. Other data suggest that alcohol may inhibit fibrinolysis. We sought to clarify these mechanisms after traumatic injury using thromboelastometry (ROTEM), hypothesizing that alcohol-related clot formation impairment may be counter-balanced by inhibited fibrinolysis. METHODS:Laboratory, demographic, clinical, and outcome data were prospectively collected from 406 critically injured trauma patients at a Level I trauma center. ROTEM and standard coagulation measures were conducted in parallel. Univariate comparisons were performed by alcohol level (EtOH), with subsequent regression analysis. RESULTS:Among 274 (58%) patients with detectable EtOH, median EtOH was 229 mg/dL. These patients were primarily bluntly injured and had lower GCS (p < 0.05) than EtOH-negative patients, but had similar admission pH and injury severity (p = NS). EtOH-positive patients had prolonged ROTEM clotting time and rate of clot formation time (CFT/α); they also had decreased fibrinolysis (max lysis %; all p < 0.05). In linear regression, for every 100 mg/dL increase in EtOH, clotting time increased by 13 seconds and fibrinolysis decreased by 1.5% (both p < 0.05). However, EtOH was not an independent predictor of transfusion requirements or mortality. In high-EtOH patients with coagulopathic ROTEM tracings, transfusion rates were significantly lower than expected, relative to EtOH-negative patients with similar ROTEM findings. CONCLUSION:As assayed by ROTEM, alcohol appears to have a bidirectional effect on coagulation in trauma, both impairing initial clot formation and inhibiting fibrinolysis. This balancing of mechanisms may explain lack of correlation between altered ROTEM and coagulopathy-related outcomes. Viscoelastic testing should be used with caution in intoxicated trauma patients. LEVEL OF EVIDENCE:Epidemiological study, level III.

BACKGROUND Impaired postinjury platelet aggregation is common, but the effect of transfusion on this remains unclear. Data suggest that following injury platelet transfusion may not correct impaired platelet aggregation, and impaired platelet aggregation may not predict the need for platelet transfusion. We sought to further investigate platelet aggregation responses to transfusions, using regression statistics to isolate the independent effects of transfusions given in discrete time intervals from injury on both immediate and longitudinal platelet aggregation. We hypothesized that platelet aggregation response to platelet transfusion increases over time from injury. METHODS Serial (0-96 hours) blood samples were collected from 248 trauma patients. Platelet aggregation was assessed in vitro with impedance aggregometry stimulated by adenosine diphosphate, collagen, and thrombin receptor-activating peptide-6. Using regression, transfusion exposure was modeled against platelet aggregation at each subsequent timepoint and adjusted for confounders (Injury Severity Score, international normalized ratio (INR), base deficit, platelet count, and interval transfusions). The expected change in platelet aggregation at each timepoint under the intervention of transfusion exposure was calculated and compared with the observed platelet aggregation. RESULTS The 248 patients analyzed were severely injured (Injury Severity Score, 21 ± 19), with normal platelet counts (mean, 268 × 10/L ± 90), and 62% were transfused in 24 hours. The independent effect of transfusions on subsequent platelet aggregation over time was modeled with observed platelet aggregation under hypothetical treatment of one unit transfusion of blood, plasma, or platelets. Platelet transfusions had increasing expected effects on subsequent platelet aggregation over time, with the maximal expected effect occurring late (4-5 days from injury). CONCLUSION Controversy exists on whether transfusions improve impaired postinjury platelet aggregation. Using regression modeling, we identified that expected transfusion effects on subsequent platelet aggregation are maximal with platelet transfusion given late after injury. This is critical for tailored resuscitation, identifying a potential early period of resistance to platelet transfusion that resolves by 96 hours. LEVEL OF EVIDENCE Therapeutic, level V.

Examine the effect of different types of firearms on readmission due to acute stress disorder (ASD) and/or post-traumatic stress disorder (PTSD) in firearm-injury victims.Survivors of firearm-related injuries suffer long-term sequelae such as disability, work loss, and deterioration in the quality of life. There is a paucity of data describing the long-term mental health outcomes in these patients.We performed a 5-year (2011-2015) analysis of the Nationwide Readmission Database. All adult patients with firearm injuries were stratified into 3 groups by firearm type: handgun, shotgun, and semiautomatic rifle. Outcome measures were the incidence and predictors of ASD/PTSD.A total of 100,704 victims of firearm-related injuries were identified, of which 13.3% (n = 13,393) were readmitted within 6 months of index hospitalization, 6.7% (n = 8970) of these due to ASD/PTSD. Mean age was 34 ± 14 years, 88% were men. Of those readmitted due to ASD/PTSD, 24% (n = 2153) sustained a handgun-related injury on index hospitalization, 12% (n = 1076) shotgun, and 64% (n = 5741) semiautomatic gun (P = 0.039). On regression analysis, semiautomatic gun and shotgun victims had higher odds of developing ASD/PTSD upon readmission [odds ratio (OR): 2.05 (1.10-4.12) and OR: 1.41 (1.08-2.11)] compared to handgun. Female sex [OR: 1.79 (1.05-3.05)] and younger age representing those younger than 25 years [OR: 4.66 (1.12-6.74)] were also independently associated with higher odds of ASD/PTSD.Apart from the lives lost, survivors of semiautomatic rifle- and shotgun-related injuries suffer long-term mental health sequalae. These secondary and debilitating mental health outcomes are important considerations for capturing the overall burden of the disease.

BACKGROUND:Platelet (Plt) derived-extracellular vesicles (Plt-EVs) have hemostatic properties similar to Plts. In addition to hemostasis, Plts also function to stabilize the vasculature and maintain endothelial cell (EC) barrier integrity. We hypothesized that Plt-EVs would inhibit vascular endothelial cell permeability, similar to fresh Plts. To investigate this hypothesis we utilized in vitro and in vivo models of vascular endothelial compromise and bleeding. METHODS:In vitro: Plt-EVs were isolated by ultracentrifugation and characterized for Plt markers and particle size distribution. Effects of Plts and Plt-EVs on endothelial barrier function was assessed by trans - endothelial electrical resistance (TEER) measurements and histological analysis of endothelial junction proteins. Hemostatic potential of Plt-EVs and Plts were assessed by multiple electrode Plt aggregometry. In vivo: The effects of Plts and Plt-EVs on vascular permeability and bleeding were assessed in NOD-SCID mice by an established Miles Assay of vascular permeability and a tail snip bleeding assay. RESULTS:In vitro: Plt-EVs displayed exosomal size distribution and expressed Plt specific surface markers. Plts and Plt-EVs decreased EC permeability and restored EC junctions after thrombin challenge. Multiplate aggregometry revealed that Plt-EVs enhanced Thrombin Receptor Activating Peptide (TRAP) mediated aggregation of whole blood, whereas Plts enhanced TRAP, Arachidonic Acid (ASPI), Collagen, and Adenosine Diphosphate (ADP) mediated aggregation. In vivo: Plt-EVs are equivalent to Plts in attenuating VEGF-A induced vascular permeability and uncontrolled blood loss in a tail snip hemorrhage model. CONCLUSION:Our study is the first to report that Plt-EVs might provide a feasible product for transfusion in trauma patients to attenuate bleeding, inhibit vascular permeability and mitigate the endotheliopathy of trauma (EOT). STUDY TYPE:Original Article LEVEL OF EVIDENCE: This is a pre-clinical study so it does not confirm to the level of evidence table for all clinical studies and case reports.

BACKGROUND Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality. METHODS Eighteen trauma centers prospectively enrolled all adult trauma patients at the time of death during December 2015 to August 2017. Immediately following death, attending providers adjudicated the primary and contributing secondary COD using standardized definitions. Data were confirmed by autopsies, if performed. RESULTS One thousand five hundred thirty-six patients were enrolled with a median age of 55 years (interquartile range, 32-75 years), 74.5% were male. Penetrating mechanism (n = 412) patients were younger (32 vs. 64, p < 0.0001) and more likely to be male (86.7% vs. 69.9%, p < 0.0001). Falls were the most common mechanism of injury (26.6%), with gunshot wounds second (24.3%). The most common overall primary COD was traumatic brain injury (TBI) (45%), followed by exsanguination (23%). Traumatic brain injury was nonsurvivable in 82.2% of cases. Blunt patients were more likely to have TBI (47.8% vs. 37.4%, p < 0.0001) and penetrating patients exsanguination (51.7% vs. 12.5%, p < 0.0001) as the primary COD. Exsanguination was the predominant prehospital (44.7%) and early COD (39.1%) with TBI as the most common later. Penetrating mechanism patients died earlier with 80.1% on day 0 (vs. 38.5%, p < 0.0001). Most deaths were deemed disease-related (69.3%), rather than by limitation of further aggressive care (30.7%). Hemorrhage was a contributing cause to 38.8% of deaths that occurred due to withdrawal of care. CONCLUSION Exsanguination remains the predominant early primary COD with TBI accounting for most deaths at later time points. Timing and primary COD vary significantly by mechanism. Contemporaneous adjudication of COD is essential to elucidate the true understanding of patient outcome, center performance, and future research. LEVEL OF EVIDENCE Epidemiologic, level II.

Background Trauma has long been considered unpredictable. Artificial neural networks (ANN) have recently shown the ability to predict admission volume, acuity, and operative needs at a single trauma center with very high reliability. This model has not been tested in a multicenter model with differing climate and geography. We hypothesize that an ANN can accurately predict trauma admission volume, penetrating trauma admissions, and mean Injury Severity Score (ISS) with a high degree of reliability across multiple trauma centers. Methods Three years of admission data were collected from five geographically distinct US Level I trauma centers. Patients with incomplete data, pediatric patients, and primary thermal injuries were excluded. Daily number of traumas, number of penetrating cases, and mean ISS were tabulated from each center along with National Oceanic and Atmospheric Administration data from local airports. We trained a single two-layer feed-forward ANN on a random majority (70%) partitioning of data from all centers using Bayesian Regularization and minimizing mean squared error. Pearson's product-moment correlation coefficient was calculated for each partition, each trauma center, and for high- and low-volume days (>1 standard deviation above or below mean total number of traumas). Results There were 5,410 days included. There were 43,380 traumas, including 4,982 penetrating traumas. The mean ISS was 11.78 (SD = 6.12). On the training partition, we achieved R = 0.8733. On the testing partition (new data to the model), we achieved R = 0.8732, with a combined R = 0.8732. For high- and low-volume days, we achieved R = 0.8934 and R = 0.7963, respectively. Conclusion An ANN successfully predicted trauma volumes and acuity across multiple trauma centers with very high levels of reliability. The correlation was highest during periods of peak volume. This can potentially provide a framework for determining resource allocation at both the trauma system level and the individual hospital level. Level of evidence Care Management, level IV.

BackgroundPrevious work proposed a Massive Transfusion Score (MTS) calculated from values obtained in the emergency department to predict likelihood of massive transfusion (MT). We hypothesized the MTS could be used at Hour 6 to differentiate who continues to require balanced resuscitation in Hours 7 to 24 and to predict death at 28 days.MethodsWe prospectively enrolled patients in whom the MT protocol was initiated from 2005 to 2011. Data including timing of blood products were determined at Hours 0, 6, 12, and 24. For each patient, transfusion needs were defined based on either an inappropriately low hemoglobin response to transfusion or a hemoglobin decrease of greater than 1 g/dL if no transfusion. Timing and cause of death were used to account for survivor bias. Multivariate logistic regression was used to determine independent predictors of outcome.ResultsA total of 190 MT protocol activations were included, and by Hour 6, 61% required 10 U or greater packed red blood cells. Calculated at initial presentation, a revised MTS (systolic blood pressure < 90 mm Hg, base deficit ≥ 6, temperature < 35.5°C, international normalized ratio > 1.5, hemoglobin < 11 g/dL) was superior to the original MTS (including heart rate ≥ 120 beats per minute, Focused Assessment With Sonography in Trauma [FAST] status, mechanism) or the Assessment of Blood Consumption (ABC) score for predicting MT (area under the curve [AUC] MT at 6 hours, 0.68; 95% confidence interval [CI], 0.57-0.79; at 24 hours, 0.72; 0.61-0.83; p < 0.05). For those alive at Hour 6, the revised MTS was predictive of future packed red blood cell need (AUC, 0.87) in Hours 7 to 12, 24-hour mortality (AUC, 0.95), and 28-day mortality (AUC, 0.77). For each additional positive trigger of the MTS at Hour 6, the odds of death at 24 hours and 28 days were substantially increased (24-hour odds ratio, 4.6; 95% CI, 2.3-9.3; 28-day odds ratio, 2.2; 95% CI, 1.5-3.2; p < 0.0001).ConclusionEarly end points of resuscitation adopted from the components of the revised MTS are predictive of ongoing transfusion. Failure to normalize these components by Hour 6 portends a particularly poor prognosis.Level of evidencePrognostic study, level 3.

BACKGROUND: Payers have approached select complications as never events, yet there is rationale that achieving a zero incidence of these events is impractical. Prior 2005 National Trauma Data Bank (NTDB) analysis showed high rates (37%) of centers reporting no complications data making national estimates for determining standardized complication rates difficult to ascertain. METHODS: The 2008–2012 NTDB National Sample Program nationally weighted files were used to calculate yearly national estimates. Rates were compared in all centers and those reporting complications data. Hospital characteristics were compared using Student t test. In 2011, an other complication category was introduced; overall rates were calculated with and without this category. Yearly estimates were reported for patients receiving care within centers reporting complications data. RESULTS: From 2008–2012 NTDB, there were raw data on 3,657,884 patients. A total of 594,894 patients (16.3%) experienced one or more complications (82.7% one complication; 17.3% two or more complications). Excluding the other complication category, the overall weighted rate was 8.4% to 9.2%. Pneumonia was the most common complication (2.7–3.0%), occurring at twice the 2005 rate. The number of centers reporting no complications data dropped to 8.1% in 2011 (2008, 14.5%; 2009, 18.2%; 2010, 15.9%; 2012, 8.9%). By 2012, nearly all level I centers reported complications, whereas 46.4% of level IVs reported none (I 0.5%, II 2.7%, III 8.5%, p = 0.04). Data were reported the least frequently in nonteaching hospitals (15.8%, p = 0.007), those in the South (19.6%, p = 0.007), and those with less than 200 beds (23.6%, p = 0.005). CONCLUSION: Overall rates of complications from 2008 to 2012 were nearly twofold higher than 2005 data. Reporting has increased, and NTDB may provide a valuable platform for establishing rational and achievable measures for specific complications. LEVEL OF EVIDENCE: Prognostic and epidemiological, level IV.

BACKGROUND:Severely injured patients often progress from early hypocoagulable to normal and eventually hypercoagulable states, developing increased risk for venous thromboembolism (VTE). Prophylactic anticoagulation can decrease this risk, but its initiation is frequently delayed for extended periods due to concerns for bleeding. To facilitate timely introduction of VTE chemoprophylaxis, we characterized the transition from hypo- to hypercoagulability and hypothesized that trauma-induced coagulopathy resolves within 24 hours after injury. METHODS:Serial blood samples were collected prospectively from critically injured patients for 120 hours after arrival at an urban Level I trauma center. Extrinsic thromboelastometry maximum clot firmness was used to classify patients as hypocoagulable (HYPO, 71 mm) at each time point. Changes in coagulability over hospital course, VTE occurrence, and timing of prophylaxis initiation were analyzed. RESULTS:898 patients (median Injury Severity Score, 13; mortality, 12%; VTE, 8%) were enrolled. Upon arrival, 3% were HYPO (90% NORM, 7% HYPER), which increased to 9% at 6 hours before down-trending. Ninety-seven percent were NORM by 24 hours, and 53% were HYPER at 120 hours. Median maximum clot firmness began in the NORM range, up-trended gradually, and entered the HYPER range at 120 hours. Patients with traumatic brain injury (TBI) followed a similar course and were not more HYPO at any time point than those without TBI. Failure to initiate prophylaxis by 72 hours was predicted by TBI and associated with VTE development (27% vs 16%, p < 0.05). CONCLUSIONS:Regardless of injury pattern, trauma-induced coagulopathy largely resolves within 24 hours, after which hypercoagulability becomes increasingly more prevalent. Deferring initiation of chemoprophylaxis, which is often biased toward patients with intracranial injuries, is associated with VTE development. LEVEL OF EVIDENCE:Prognostic study, level III; Therapeutic, level IV.

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.

Background Injury to the blood-brain barrier exposes endothelium rich in von Willebrand factor (vWF), which may play a role in altered platelet aggregation following traumatic brain injury (TBI). Ristocetin is an antimicrobial substance that induces vWF-mediated aggregation of platelets. We examined these mechanisms in injured patients by measuring the aggregation response of platelets to stimulating agonists (including ristocetin) via whole-blood multiple-electrode platelet aggregometry. We hypothesized that patients with TBI have an altered platelet aggregation response to ristocetin stimulation compared with patients without TBI. Methods Blood was collected from 233 trauma patients without thrombocytopenia. Platelet aggregation was assessed using multiple-electrode platelet aggregometry (Multiplate). Platelet aggregation response to stimulating agonists collagen, thrombin receptor-activating peptide 6, adenosine diphosphate, arachidonic acid, and ristocetin was measured. Factor activity was measured. Results Of the 233 patients, 23% had TBI. There were no differences in platelet aggregation responses to any agonists between TBI and non-TBI patients except ristocetin. Platelet aggregation response to ristocetin stimulation was significantly lower in TBI patients (p = 0.03). Patients with TBI also had higher factor VIII activity (215% vs. 156%, p = 0.01). In multivariate analysis, there was a significant independent association of impaired platelet aggregation response to ristocetin stimulation with TBI (odds ratio, 3.05; p = 0.04). Conclusions Given the importance of platelets in hemostasis, understanding the mechanisms of impaired platelet aggregation following injury is critical. The impaired platelet aggregation response to ristocetin stimulation and corresponding increase in factor VIII activity in TBI patients may be secondary to a TBI-induced effect on vWF quantity (due to injury-driven consumption of vWF) or vWF function with resultant increase in circulating factor VIII activity (due to impaired carrying capacity of vWF). Given there are multiple known therapies for vWF deficits including desmopressin, purified and recombinant vWF, and estrogens, these lines of investigation are particularly compelling in patients with TBI and hemorrhage. Level of evidence Prognostic study, level II.

BackgroundSince 1967, in California it has been illegal to openly carry a loaded firearm in public except when engaged in hunting or law enforcement. However, beginning January 1, 2012, public open carry of unloaded handguns also became illegal. Fatal and non-fatal (NF) firearm injuries were examined before and after adoption of the 2012 ban to quantify the effect of the new law on public health.MethodsState-level data were obtained directly from California and nine other US state inpatient and emergency department (ED) discharge databases, and the Centers for Disease Control Web-Based Injury Statistics Query and Reporting System. Case numbers of firearm fatalities, NF hospitalizations, NF ED visits, and state-level population estimates were extracted. Each incident was classified as unintentional, self-inflicted, or assault. Crude incidence rates were calculated. The strength of gun laws was quantified using the Brady grade. There were no changes to open carry in these nine states during the study. Using a difference-in-difference technique, the rate trends 3 years preban and postban were compared.ResultsThe 2012 open carry ban resulted in a significantly lower incident rate of both firearm-related fatalities and NF hospitalizations (pDiscussionOpen carry ban decreases fatalities and healthcare utilization even in a state with baseline strict gun laws. The most significant impact is from decreasing firearm-related fatal and NF assaults.Level of evidenceIII, epidemiology.

BackgroundOutcome after traumatic injury has typically been limited to the determination at time of discharge or brief follow-up. This study investigates the natural history of long-term survival after trauma.MethodsAll highest-level activation patients prospectively enrolled in an ongoing cohort study from 2005 to 2012 were selected. To allow for long-term follow-up, patients had to be enrolled at least 1 year before the latest available data from the National Death Index (NDI, 2013). Time and cause of mortality was determined based on death certificates. Survival status was determined by the latest date of either care in our institution or NDI query. Kaplan-Meier curves were created stratified for Injury Severity Score (ISS). Survival was compared with estimated actuarial survival based on age, sex, and race.ResultsA total of 908 highest-level activation patients (median ISS, 18) were followed up for a median 1.7 years (interquartile range 1.0-2.9; maximum, 9.8 years). Survival data were available on 99.8%. Overall survival was 73% (663 of 908). For those with at least 2-year follow-up, survival was only 62% (317 of 509). Severity of injury predicted long-term survival (p < 0.0001) with those having ISS of 25 or greater with the poorest outcome (57% survival at 5 years). For all ISS groups, survival was worse than predicted actuarial survival (p < 0.001). When excluding early deaths (≤30 days), observed survival was still significantly lower than estimated actuarial survival (p < 0.002). Eighteen percent (44 of 245 deaths) of all deaths occurred after 30 days. Among late deaths, 53% occurred between 31 days and 1 year after trauma. Trauma-related mortality was the leading cause of postdischarge death, accounting for 43% of the late deaths.ConclusionPostdischarge deaths represent a significant percentage of total trauma-related mortality. Despite having "survived" to leave the hospital, long-term survival was worse than predicted actuarial survival, suggesting that the mortality from injury does not end at "successful" hospital discharge.Level of evidencePrognostic study, level III.

BACKGROUND: Unconscious patients who present after being "found down" represent a unique triage challenge. These patients are selected for either trauma or medical evaluation based on limited information and have been shown in a single-center study to have significant occult injuries and/or missed medical diagnoses. We sought to further characterize this population in a multicenter study and to identify predictors of mistriage. METHODS: The Western Trauma Association Multicenter Trials Committee conducted a retrospective study of patients categorized as found down by emergency department triage diagnosis at seven major trauma centers. Demographic, clinical, and outcome data were collected. Mistriage was defined as patients being admitted to a non-triage-activated service. Logistic regression was used to assess predictors of specified outcomes. RESULTS: Of 661 patients, 33% were triaged to trauma evaluations, and 67% were triaged to medical evaluations; 56% of all patients had traumatic injuries. Trauma-triaged patients had significantly higher rates of combined injury and a medical diagnosis and underwent more computed tomographic imaging; they had lower rates of intoxication and homelessness. Among the 432 admitted patients, 17% of them were initially mistriaged. Even among properly triaged patients, 23% required cross-consultation from the non-triage-activated service after admission. Age was an independent predictor of mistriage, with a doubling of the rate for groups older than 70 years. Combined medical diagnosis and injury was also predictive of mistriage. Mistriaged patients had a trend toward increased late-identified injuries, but mistriage was not associated with increased length of stay or mortality. CONCLUSION: Patients who are found down experience significant rates of mistriage and triage discordance requiring cross-consultation. Although the majority of found down patients are triaged to nontrauma evaluation, more than half have traumatic injuries. Characteristics associated with increased rates of mistriage, including advanced age, may be used to improve resource use and minimize missed injury in this vulnerable patient population. LEVEL OF EVIDENCE: Epidemiologic study, level III. Language: en

BACKGROUND: Although obese patients have high thrombosis rates following injury, the role of obesity in coagulation after trauma remains unknown. We hypothesized that body mass index (BMI) is independently associated with increased measures of hypercoagulability longitudinally after injury. METHODS: Data were prospectively collected for 377 consecutive highest-level trauma activation patients with a BMI of 18.5 kg/m 2 or greater. Standard coagulation measures, citrated kaolin and functional fibrinogen thromboelastography, as well as clotting factors were measured at 0 hour to 120 hours. BMI categories were defined as normal weight (18.5Y24.99 kg/m 2 ), overweight (25Y29.99 kg/m 2 ), and obese (Q30 kg/m 2 ). RESULTS: The 377 patients were mostly male (81%) and had blunt injury (61%), with a median BMI of 25.8 kg/m 2 . Of the patients, 42% were normal weight (median BMI, 22.5 kg/m 2 ). There were no differences in age, sex, Injury Severity Score (ISS), or base deficit between groups. There were no differences in admission international normalized ratio/partial thromboplastin time or factors II, V, VII, VIII, and X; antithrombin III; or protein C. However, obese patients had higher admission platelet counts (303 10 9 /L vs. 269 10 9 /L, p = 0.004), lower D-dimer (1.88 Kg/mL vs. 4.00 Kg/mL, p = 0.004), and a trend toward higher factor IX (134% vs. 119% activity, p = 0.042) compared with normal weight patients. Measured by thromboelastography, clot strength (maximum amplitude) and functional fibrinogen level (FLEV) were also higher on admission for obese patients (maximum amplitude, 65.7 mm vs. 63.4 mm, p = 0.016; FLEV, 407 mg/dL vs. 351 mg/dL, p = 0.008). In multiple linear regression, the relationship of BMI to clot strength, FLEV, and factor IX persisted through 24 hours. Similarly, the relationship of BMI and platelet count persisted through 120 hours (all p G 0.05). In multiple logistic regression, for every 5-kg/m 2 increase in BMI, there was an 85% increase in odds of thromboembolic complication (odds ratio, 1.85; 95% confidence interval, 1.13Y3.08; p = 0.017). CONCLUSION: Obese trauma patients are hypercoagulable compared with their similarly injured normal-weight counterparts, which persists longitudinally after injury. The significance of this hypercoagulability requires elucidation for guidance of anticoagulation in this at-risk group. (J Trauma Acute Care Surg. 2015;78: 30Y38. Copyright* 2015 Wolters Kluwer Health, Inc. All rights reserved.) LEVEL OF EVIDENCE: Prognostic study, level III.

OBJECTIVESThe mortality of patients with Clostridium difficile–associated disease (CDAD) requiring surgery continues to be very high. Loop ileostomy (LI) was introduced as an alternative procedure to total colectomy (TC) for CDAD by a single-center study. To date, no reproducible results have been p

BACKGROUND International normalized ratio (INR) and partial thromboplastin time (PTT) are used interchangeably to diagnose acute traumatic coagulopathy but reflect disparate activation pathways. In this study, we identified injury/patient characteristics and coagulation factors that drive contact pathway, tissue factor pathway (TF), and common pathway dysfunction by examining injured patients with discordant coagulopathies. We hypothesized that patients with INR/PTT discordance reflect differing phenotypes representing contact versus tissue factor pathway perturbations and that characterization will provide targets to guide individualized resuscitation. METHODS Plasma samples were prospectively collected from 1,262 critically injured patients at a single Level I trauma center. Standard coagulation measures and an extensive panel of procoagulant and anticoagulant factors were assayed and analyzed with demographic and outcome data. RESULTS Fourteen percent of patients were coagulopathic on admission. Among these, 48% had abnormal INR and PTT (BOTH), 43% had isolated prolonged PTT (PTT-CONTACT), and 9% had isolated elevated INR (INR-TF). PTT-CONTACT and BOTH had lower Glasgow Coma Scale score than INR-TF (p < 0.001). INR-TF had decreased factor VII activity compared with PTT-CONTACT, whereas PTT-CONTACT had decreased factor VIII activity compared with INR-TF. All coagulopathic patients had factor V deficits, but activity was lowest in BOTH, suggesting an additive downstream effect of disordered activation pathways. Patients with PTT-CONTACT received half as much packed red blood cell and fresh frozen plasma as did the other groups (p < 0.001). Despite resuscitation, mortality was higher for coagulopathic patients; mortality was highest in BOTH and higher in PTT-CONTACT than in INR-TF (71%, 60%, 41%; p = 0.04). CONCLUSIONS Discordant phenotypes demonstrate differential factor deficiencies consistent with dysfunction of contact versus tissue factor pathways with additive effects from common pathway dysfunction. Recognition and treatment of pathway-specific factor deficiencies driving different coagulopathic phenotypes in injured patients may individualize resuscitation and improve outcomes. LEVEL OF EVIDENCE Prognostic/epidemiological study, level II.

Background Mounting evidence highlighting the benefits of hemostatic resuscitation has led to a renewed interest in whole blood (WB) and reconstituted WB (RWB). However, few data exist to characterize the clotting profiles of these variants. This study characterizes banked WB variants and RWB in standard 1:1:1 and 2:1:1 transfusion ratios of packed red blood cells, fresh frozen plasma, and platelets (PLTs). We hypothesized that the global hemostatic profile of 1:1:1 RWB is superior to 2:1:1 RWB and that PLT-modified WB (MWB) is superior to 1:1:1 RWB. Methods Twenty-three units of packed red blood cells, fresh frozen plasma, and PLTs were obtained from the regional blood collection center and mixed to create 23 1:1:1 and 23 2:1:1 RWB units. Freshly donated WB units were obtained and used to create 11 of each nonmodified WB (NMWB) (room temperature and cooled) and MWB (room temperature and cooled) variants. International normalized ratio (INR)/partial thromboplastin time (PTT), complete blood cell count, functional studies, and an extensive panel of procoagulant and anticoagulant factor assays were performed on all products. Results The 1:1:1 RWB had significantly lower INR and PTT (1.31 vs. 1.55, p = 0.0029; 42 seconds vs. 50 seconds, p = 0.0008) and higher activity of factors II, V, VII, VIII, IX, and X; antithrombin III, as well as protein C and higher fibrinogen levels than did 2:1:1 RWB (factor IX, 86% vs. 70%, p = 0.0313; fibrinogen, 242 mg/dL vs. 202 mg/dL, p = 0.0385). There were no differences in INR/PTT or factor activity between MWB and NMWB. However, MWB had greater maximum clot firmness (MCF) by rotational thromboelastometry tissue factor-activated extrinsic clotting cascade measures than did NMWB (MCF, 61 mm vs. 50 mm, p = 0.0031). MWB also had greater MCF by rotational thromboelastometry tissue factor-activated extrinsic clotting cascade measures than did 1:1:1 RWB (MCF, 61 mm vs. 45 mm, p = 0.0005). Conclusion Although 1:1:1 RWB had a superior clotting profile relative to 2:1:1 RWB, MWB exhibited even better global hemostasis than did 1:1:1 RWB. Characterization of factor-level and functional clotting differences between WB variants is imperative for understanding the clinical benefits of hemostatic resuscitation.

BACKGROUND Respiratory failure after acute spinal cord injury (SCI) is well recognized, but data defining which patients need long-term ventilator support and criteria for weaning and extubation are lacking. We hypothesized that many patients with SCI, even those with cervical SCI, can be successfully managed without long-term mechanical ventilation and its associated morbidity. METHODS Under the auspices of the Western Trauma Association Multi-Center Trials Group, a retrospective study of patients with SCI at 14 major trauma centers was conducted. Comprehensive injury, demographic, and outcome data on patients with acute SCI were compiled. The primary outcome variable was the need for mechanical ventilation at discharge. Secondary outcomes included the use of tracheostomy and development of acute lung injury and ventilator-associated pneumonia. RESULTS A total of 360 patients had SCI requiring mechanical ventilation. Sixteen patients were excluded for death within the first 2 days of hospitalization. Of the 344 patients included, 222 (64.5%) had cervical SCI. Notably, 62.6% of the patients with cervical SCI were ventilator free by discharge. One hundred forty-nine patients (43.3%) underwent tracheostomy, and 53.7% of them were successfully weaned from the ventilator, compared with an 85.6% success rate among those with no tracheostomy (p < 0.05). Patients who underwent tracheostomy had significantly higher rates of ventilator-associated pneumonia (61.1% vs. 20.5%, p < 0.05) and acute lung injury (12.8% vs. 3.6%, p < 0.05) and fewer ventilator-free days (1 vs. 24 p < 0.05). When controlled for injury severity, thoracic injury, and respiratory comorbidities, tracheostomy after cervical SCI was an independent predictor of ventilator dependence with an associated 14-fold higher likelihood of prolonged mechanical ventilation (odds ratio, 14.1; 95% confidence interval, 2.78-71.67; p < 0.05). CONCLUSION While many patients with SCI require short-term mechanical ventilation, the majority can be successfully weaned before discharge. In patients with SCI, tracheostomy is associated with major morbidity, and its use, especially among patients with cervical SCI, deserves further study. LEVEL OF EVIDENCE Prognostic study, level III.

Early diagnosis and intervention are paramount for improving the likelihood of a favorable outcome for traumatic vascular injuries. As technology has rapidly diversified, the diagnostic and therapeutic approaches available for vascular injuries have evolved. Mortality and morbidity from vascular injury have declined over the last decade. The use of vascular shunts and tourniquets has become standard of care in military medicine.

Acute lung injury following trauma resuscitation remains a concern despite recent advances. With the use of the PROMMTT study population, the risk of hypoxemia and potential modifiable risk factors are studied.Patients with survival for 24 hours or greater with at least one intensive care unit day were included in the analysis. Hypoxemia was categorized using the Berlin definition for adult respiratory distress syndrome: none (PaO₂-to-FIO₂ ratio [P/F]300 mm Hg), mild (P/F, 201-300 mm Hg), moderate (P/F, 101-200 mm Hg) or severe (P/F ≤ 100 mm Hg). The cohort was dichotomized into those with none or mild hypoxemia and those with moderate or severe injury. Early resuscitation was defined as that occurring 0 hour to 6 hours from arrival; late resuscitation was defined as that occurring 7 hours to 24 hours. Multivariate logistic regression models were developed controlling for age, sex, mechanisms of injury, arrival physiology, individual Abbreviated Injury Scale (AIS) scores, blood transfusions, and crystalloid administration.Of the patients 58.7% (731 of 1,245) met inclusion criteria. Hypoxemia occurred in 69% (mild, 24%; moderate, 28%; severe, 17%). Mortality was highest (24%) in the severe group. During early resuscitation (0-6 h), logistic regression revealed age (odd ratio [OR], 1.02; 95% confidence interval [CI], 1.00-1.04), chest AIS score (OR, 1.31; 95% CI, 1.10-1.57), and intravenously administered crystalloid fluids given in 500 mL increments (OR, 1.12; 95% CI, 1.01-1.25) as predictive of moderate or severe hypoxemia. During late resuscitation, age (OR, 1.02; 95% CI, 1.00-1.04), chest AIS score (OR, 1.33; 95% CI, 1.11-1.59), and crystalloids given during this period (OR, 1.05; 95% CI, 1.01-1.10) were also predictive of moderate-to-severe hypoxemia. Red blood cell, plasma, and platelet transfusions (whether received during early or late resuscitation) failed to demonstrate an increased risk of developing moderate/severe hypoxemia.Severe chest injury, increasing age, and crystalloid-based resuscitation, but not blood transfusions, were associated with increased risk of developing moderate-to-severe hypoxemia following injury.

BACKGROUND Acute traumatic coagulopathy affects 20% to 30% of trauma patients, but the extensive collinearity of the coagulation cascade complicates attempts to clarify global clotting factor dysfunction. This study aimed to characterize phenotypes of clotting factor dysfunction and their contributions to mortality after major trauma. METHODS This prospective cohort study examines all adult trauma patients of the highest activation level presenting to San Francisco General Hospital between February 2005 and February 2015. Factors II, V, VII, VIII, IX, and X and protein C activity on admission and mortality status at 28 days were assessed. Predictors of 28-day mortality in univariate analysis were included in multiple logistic regression controlling for traumatic brain injury (TBI), acidosis, age, and mechanism of injury. Principal component analysis was utilized to identify phenotypic coagulation. RESULTS Complete coagulation factor data were available for 876 (61%) of 1,429 patients. In multiple logistic regression, factors V (odds ratio [OR], 0.86; 95% confidence interval [CI], 0.76-0.97), VIII (OR, 0.97; 95% CI, 0.95-0.99), and X (OR, 0.79; 95% CI, 0.68-0.92) and protein C (OR, 1.17; 95% CI, 1.05-1.30) significantly predicted 28-day mortality after controlling for age, base deficit, mechanism of injury, and TBI. Principal component analysis identified two significant principal components (Phenotypes 1 and 2) that accounted for 66.3% of the total variance. Phenotype 1 (factors II, VII, IX, and X and protein C abnormalities) explained 49.3% and was associated with increased injury, coagulopathy, TBI, and mortality. Phenotype 2 (factors V and VIII abnormalities) explained 17.0% and was associated with increased coagulopathy, blunt injury, and mortality. Only Phenotype 2 remained significantly associated with 28-day mortality in multiple logistic regression. CONCLUSIONS Principal component analysis identified two distinct phenotypes within the entirety of global clotting factor abnormalities, and these findings substantiate the crucial association of factors V and VIII on mortality following trauma. This may be the first step toward identifying unique phenotypes after injury and personalizing hemostatic resuscitation. LEVEL OF EVIDENCE Prognostic study, level III.

Background Recent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury. Methods Trauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs. Results Critically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly. Discussion In this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories. Level of evidence III Study type Prognostic/epidemiological

Sepsis remains a highly lethal entity resulting in more than 200 000 deaths in the USA each year. The in-hospital mortality approaches 30% despite advances in critical care during the last several decades. The direct health care costs in the USA exceed $24 billion dollars annually and continue to escalate each year especially as the population ages. The Surviving Sepsis Campaign published their initial clinical practice guidelines for the management of severe sepsis and septic shock in 2004. Updated versions were published in 2008, 2012 and most recently in 2016 following the convening of the Third International Consensus Definitions Task Force. This task force was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine to address prior criticisms of the multiple definitions used clinically for sepsis-related illnesses. In the 2016 guidelines, sepsis is redefined by the taskforce as a life-threatening organ dysfunction caused by a dysregulated host response to infection. In addition to using the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score to more rapidly identify patients with sepsis, the task force also proposed a novel scoring system to rapidly screen for patients outside the ICU who are at risk of developing sepsis: the 'quickSOFA' (qSOFA) score. To date, the largest reductions in mortality have been associated with early identification of sepsis, initiation of a 3-hour care bundle and rapid administration of broad-spectrum antibiotics. The lack of progress in mortality reduction in sepsis treatment despite extraordinary investment of research resources underscores the variability in patients with sepsis. No single solution is likely to be universally beneficial, and sepsis continues to be an entity that should receive high priority for the development of precision health approaches for treatment.

Early predictors of massive transfusion (MT) would prevent undertriage of patients likely to require MT. This study validates triggers using the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study.All enrolled patients in PROMMTT were analyzed. The initial emergency department value for each trigger (international normalized ratio [INR], systolic blood pressure, hemoglobin, base deficit, positive result for Focused Assessment for the Sonography of Trauma examination, heart rate, temperature, and penetrating injury mechanism) was compared for patients receiving MT (≥ 10 U of packed red blood cells in 24 hours) versus no MT. Adjusted odds ratios (ORs) for MT are reported using multiple logistic regression. If all triggers were known, a Massive Transfusion Score (MTS) was created, with 1 point assigned for each met trigger.A total of 1,245 patients were prospectively enrolled with 297 receiving an MT. Data were available for all triggers in 66% of the patients including 67% of the MTs (199 of 297). INR was known in 87% (1,081 of 1,245). All triggers except penetrating injury mechanism and heart rate were valid individual predictors of MT, with INR as the most predictive (adjusted OR, 2.5; 95% confidence interval, 1.7-3.7). For those with all triggers known, a positive INR trigger was seen in 49% receiving MT. Patients with an MTS of less than 2 were unlikely to receive MT (negative predictive value, 89%). If any two triggers were present (MTS ≥ 2), sensitivity for predicting MT was 85%. MT was present in 33% with an MTS of 2 greater compared with 11% of those with MTS of less than 2 (OR, 3.9; 95% confidence interval, 2.6-5.8; p0.0005).Parameters that can be obtained early in the initial emergency department evaluation are valid predictors for determining the likelihood of MT.Diagnostic, level II.