Early Glasgow Coma Scale Score and Prediction of Traumatic Brain Injury: A Secondary Analysis of Three Harmonized Prehospital Randomized Clinical Trials.

OBJECTIVES: The prehospital prediction of the radiographic diagnosis of traumatic brain injury (TBI) in hemorrhagic shock patients has the potential to promote early therapeutic interventions. However, the identification of TBI is often challenging and prehospital tools remain limited. While the Glasgow Coma Scale (GCS) score is frequently used to assess the extent of impaired consciousness after injury, the utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is poorly understood. METHODS: We performed a post-hoc, secondary analysis utilizing data derived from three randomized prehospital clinical trials: the Prehospital Air Medical Plasma trial (PAMPER), the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport trial (STAAMP), and the Pragmatic Prehospital Type O Whole Blood Early Resuscitation (PPOWER) trial. Patients were dichotomized into two cohorts based on the presence of TBI and then further stratified into three groups based on prehospital GCS score: GCS 3, GCS 4-12, and GCS 13-15. The association between prehospital GCS score and clinical documentation of TBI was assessed. RESULTS: A total of 1,490 enrolled patients were included in this analysis. The percentage of patients with documented TBI in those with a GCS 3 was 59.5, 42.4% in those with a GCS 4-12, and 11.8% in those with a GCS 13-15. The positive predictive value (PPV) of the prehospital GCS score for the diagnosis of TBI is low, with a GCS of 3 having only a 60% PPV. Hypotension and prehospital intubation are independent predictors of a low prehospital GCS. Decreasing prehospital GCS is strongly associated with higher incidence or mortality over time, irrespective of the diagnosis of TBI. CONCLUSIONS: The ability to accurately predict the presence of TBI in the prehospital phase of care is essential. The utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is limited. The use of novel scoring systems and improved technology are needed to promote the accurate early diagnosis of TBI.

Activation and On-Scene Intervals for Severe Trauma EMS Interventions: An Analysis of the NEMSIS Database.

Objective: Time to care is a determinant of trauma patient outcomes, and timely delivery of trauma care to severely injured patients is critical in reducing mortality. Numerous studies have analyzed access to care using prehospital intervals from a Carr et al. meta-analysis of studies from 1975 to 2005. Carr et al.'s research sought to determine national mean activation and on-scene intervals for trauma patients using contemporary emergency medical services (EMS) records. Since the Carr et al. meta-analysis was published, the National Highway Traffic Safety Administration (NHTSA) created and refined the National Emergency Medical Services Information System (NEMSIS) database. We sought to perform a modern analysis of prehospital intervals to establish current standards and temporal patterns.Methods: We utilized NEMSIS to analyze EMS data of trauma patients from 2016 to 2019. The dataset comprises more than 94 million EMS records, which we filtered to select for severe trauma and stratified by type of transport and rurality to calculate mean activation and on-scene intervals. Furthermore, we explored the impact of basic life support (BLS) and advanced life support (ALS) of ground units on activation and on-scene time intervals.Results: Mean activation and on-scene intervals for ground transport were statistically different when stratified by rurality. Urban, suburban, and rural ground activation intervals were 2.60 ± 3.94, 2.88 ± 3.89, and 3.33 ± 4.58 minutes, respectively. On-scene intervals were 15.50 ± 10.46, 17.56 ± 11.27, and 18.07 ± 16.13 minutes, respectively. Mean helicopter transport activation time was 13.75 ± 7.44 minutes and on-scene time was 19.42 ± 16.09 minutes. This analysis provides an empirically defined mean for activation and on-scene times for trauma patients based on transport type and rurality. Results from this analysis proved to be significantly longer than the previous analysis, except for helicopter transport on-scene time. Shorter mean intervals were seen in ALS compared to BLS for activation intervals, however ALS on-scene intervals were marginally longer than BLS.Conclusions: With the increasing sophistication of geospatial technologies employed to analyze access to care, these intervals are the most accurate and up-to-date and should be included in access to care models.

Compensatory reserve and pulse character: Enhanced potential to predict urgency for transfusion and other life-saving interventions after traumatic injury.

BACKGROUND: Field triage of trauma patients requires timely assessment of physiologic status to determine resuscitative needs. Vital signs and rudimentary assessments such as pulse character (PC) are used by first responders to guide decision making. The compensatory reserve measurement (CRM) has demonstrated utility as an easily interpretable method for assessing patient status. We hypothesized that the ability to identify injured patients requiring transfusion and other life-saving interventions (LSI) using a measurement of pulse character could be enhanced by the addition of the CRM. METHODS: We performed a prospective observational study on 300 trauma patients admitted to a level I trauma center. CRM was recorded continuously after device placement on arrival. Patient demographics, field and trauma resuscitation unit vital signs, therapeutic interventions, and outcomes were collected. A field SBP <100 mmHg was utilized as a surrogate for abnormal PC as previously validated. A patient with a CRM threshold value of <60% was considered clinically compromised with a risk of onset of decompensated shock. Data were analyzed to assess the capacity of CRM and pulse character separately or in combination to predict LSI defined as need for transfusion, intubation, tube thoracostomy, or operative/ angiographic hemorrhage control. RESULTS: An improvement in the predictive capability for LSI, transfusion, or a composite outcome was demonstrated by the combination of CRM and PC compared to either measure alone. CONCLUSIONS: Combining PC assessment with CRM has the potential to enhance the recognition of injured patients requiring life-saving intervention thus improving sensitivity of decision support for prehospital providers.

The regional whole blood program in San Antonio, TX: A 3-year update on prehospital and in-hospital transfusion practices for traumatic and non-traumatic hemorrhage.

Low titer type O Rh-D + whole blood (LTO + WB) has become a first-line resuscitation medium for hemorrhagic shock in many centers around the World. Showing early effectiveness on the battlefield, LTO + WB is used in both the pre-hospital and in-hospital settings for traumatic and non-traumatic hemorrhage resuscitation. Starting in 2018, the San Antonio Whole Blood Collaborative has worked to provide LTO + WB across Southwest Texas, initially in the form of remote damage control resuscitation followed by in-hospital trauma resuscitation. This program has since expanded to include pediatric trauma resuscitation, obstetric hemorrhage, females of childbearing potential, and non-traumatic hemorrhage. The objective of this manuscript is to provide a three-year update on the successes and expansion of this system and outline resuscitation challenges in special populations.

Timing of repair of blunt thoracic aortic injuries in the thoracic endovascular aortic repair era.

OBJECTIVE: Thoracic endovascular aortic repair (TEVAR) is the preferred operative treatment of blunt thoracic aortic injuries (BTAIs). Its use is associated with improved outcomes compared with open surgical repair and nonoperative management. However, the optimal time from injury to repair is unknown and remains a subject of debate across different societal practice guidelines. The purpose of this study was to evaluate national trends in the management of BTAI, with a specific focus on the impact of timing of repair on outcomes. METHODS: Using the National Trauma Data Bank, we identified adult patients with BTAI between 2012 and 2017. Patients with prehospital or emergency department cardiac arrest or incomplete data sets were excluded from analysis. Patients were classified according to timing of repair: group 1, <24 hours; and group 2, ≥24 hours. The primary outcome evaluated was in-hospital mortality; secondary outcomes included overall hospital and intensive care unit length of stay. Multivariable logistic regression was performed to identify independent predictors of mortality. RESULTS: The analysis was completed for 2821 patients who underwent TEVAR for BTAI with known operative times. The overall mortality in the patient cohort was 8.4% (238/2821); 75% of patients undergoing TEVAR were repaired within 24 hours. Mortality was more than twofold greater in group 1 compared with group 2 (9.8% [207/2118] vs 4.4% [31/703]; P = .001). This mortality benefit persisted across injury severity groups and was independent of the presence of serious extrathoracic injuries. Logistic regression analysis, adjusting for age ≥65 years, Glasgow Coma Scale score ≤8, systolic blood pressure ≤90 mm Hg at admission, and serious extrathoracic injuries, showed a higher adjusted mortality in group 1 (odds ratio, 2.54; 95% confidence interval, 1.66-3.91; P = .001). CONCLUSIONS: The majority of patients with BTAI undergo endovascular repair within 24 hours of injury. Patients undergoing delayed repair have improved survival compared with those repaired within the first 24 hours of injury in spite of similar injury patterns and severity. In patients with BTAIs without signs of imminent rupture, delaying endovascular repair beyond 24 hours after injury should be considered.

Compensatory reserve detects subclinical shock with more expeditious prediction for need of life-saving interventions compared to systolic blood pressure and blood lactate.

INTRODUCTION: We conducted a prospective observational study on 205 trauma patients at a level I trauma facility to test the hypothesis that a compensatory reserve measurement (CRM) would identify higher risk for progression to shock and/or need a life-saving interventions (LSIs) earlier than systolic blood pressure (SBP) and blood lactate (LAC). METHODS: A composite outcome metric included blood transfusion, procedural LSI, and mortality. Discrete measures assessed as abnormal (ab) were SBP <90 mmHg, CRM <60%, and LAC >2.0. A graded categorization of shock was defined as: no shock (normal [n] SBP [n-SBP], n-CRM, n-LAC); sub-clinical shock (ab-CRM, n-SBP, n-LAC); occult shock (n-SBP, ab-CRM, ab-LAC); or overt shock (ab-SBP, ab-CRM, ab-LAC). RESULTS: Three patients displayed overt shock, 53 displayed sub-clinical shock, and 149 displayed no shock. After incorporating lactate into the analysis, 86 patients demonstrated no shock, 25 were classified as sub-clinical shock, 91 were classified as occult shock, and 3 were characterized as overt shock. Each shock subcategory revealed a graded increase requiring LSI and transfusion. Initial CRM was associated with progression to shock (odds ratio = 0.97; p < .001) at an earlier time than SBP or LAC. CONCLUSIONS: Initial CRM uncovers a clinically relevant subset of patients who are not detected by SBP and LAC. Our results suggest CRM could be used to more expeditiously identify injured patients likely to deteriorate to shock, with requirements for blood transfusion or procedural LSI.

Prehospital whole blood reduces early mortality in patients with hemorrhagic shock.

BACKGROUND: Low titer O+ whole blood (LTOWB) is being increasingly used for resuscitation of hemorrhagic shock in military and civilian settings. The objective of this study was to identify the impact of prehospital LTOWB on survival for patients in shock receiving prehospital LTOWB transfusion. STUDY DESIGN AND METHODS: A single institutional trauma registry was queried for patients undergoing prehospital transfusion between 2015 and 2019. Patients were stratified based on prehospital LTOWB transfusion (PHT) or no prehospital transfusion (NT). Outcomes measured included emergency department (ED), 6-h and hospital mortality, change in shock index (SI), and incidence of massive transfusion. Statistical analyses were performed. RESULTS: A total of 538 patients met inclusion criteria. Patients undergoing PHT had worse shock physiology (median SI 1.25 vs. 0.95, p < .001) with greater reversal of shock upon arrival (-0.28 vs. -0.002, p < .001). In a propensity-matched group of 214 patients with prehospital shock, 58 patients underwent PHT and 156 did not. Demographics were similar between the groups. Mean improvement in SI between scene and ED was greatest for patients in the PHT group with a lower trauma bay mortality (0% vs. 7%, p = .04). No survival benefit for patients in prehospital cardiac arrest receiving LTOWB was found (p > .05). DISCUSSION: This study demonstrated that trauma patients who received prehospital LTOWB transfusion had a greater improvement in SI and a reduction in early mortality. Patient with prehospital cardiac arrest did not have an improvement in survival. These findings support LTOWB use in the prehospital setting. Further multi-institutional prospective studies are needed.

From battlefront to homefront: creation of a civilian walking blood bank.

Hemorrhagic shock remains the leading cause of preventable death on the battlefield, despite major advances in trauma care. Early initiation of balanced resuscitation has been shown to decrease mortality in the hemorrhaging patient. To address transfusion limitations in austere environments or in the event of multiple casualties, walking blood banks have been used in the combat setting with great success. Leveraging the success of the region-wide whole blood program in San Antonio, Texas, we report a novel plan that represents a model response to mass casualty incidents.

Impact of time to repair on outcomes in patients with lower extremity arterial injuries.

BACKGROUND: Six hours has long been considered the threshold of ischemia after peripheral artery injury. However, there is a paucity of evidence regarding the impact of operative delays on morbidity and mortality in patients with lower extremity arterial injuries. METHODS: We analyzed the records of 3,441,259 injured patients entered into the National Trauma Data Bank Research Dataset from 2012 to 2015. Patients (≥16 years) with lower extremity arterial injuries were identified by International Classification of Diseases, Ninth Revision injury and procedure codes. Patients with crush injuries, patients with prehospital or emergency department cardiac arrest, those not transferred directly from point of injury, and patients in whom a nonoperative management strategy was attempted were excluded from analysis. RESULTS: We examined the data from 4406 patients with lower extremity arterial injuries; 85% of the patients were male, with a mean age of 35 years. The overall mortality in this cohort was 3.2% (143/4406); the amputation rate was 11.3% (499/4406). Using a multivariate logistic regression model, blunt mechanisms of injury, increased time from injury to operating room arrival, nerve injury, associated lower extremity fractures, increased age, and Injury Severity Score were associated with increased amputation risk. The amputation rate in those undergoing repair within 60 minutes was 6% compared with 11.7% and 13.4% in those undergoing repair after 1 to 3 hours and 3 to 6 hours, respectively. CONCLUSIONS: Optimal limb salvage is achieved when revascularization of lower extremity arterial injury occurs within 1 hour of injury. To improve survival and recovery after extremity arterial injury, efforts should be focused on strategies to expedite reperfusion of the injured limb.

Outcomes of traumatic hemorrhagic shock and the epidemiology of preventable death from injury.

The majority of potentially preventable deaths after trauma are related to hemorrhage and occur early after injury, with the largest number of deaths occurring before hospital arrival. Approximately one-fourth of trauma deaths may be potentially preventable through early medical and surgical interventions. Interventions dedicated to bleeding control and hemostatic resuscitation have demonstrated merit in decreasing hemorrhagic injury mortality. Advancing these novel strategies to the casualty in the prehospital phase of care, particularly in tactical or austere environments, may prove beneficial for hemorrhage mitigation to temporize the window of survival to definitive care. Future studies of resuscitation and survival after traumatic injury must include analysis of prehospital deaths to fully understand the outcomes of early interventions.

Give the trauma patient what they bleed, when and where they need it: establishing a comprehensive regional system of resuscitation based on patient need utilizing cold-stored, low-titer O+ whole blood.

BACKGROUND: Despite countless advancements in trauma care a survivability gap still exists in the prehospital setting. Military studies clearly identify hemorrhage as the leading cause of potentially survivable prehospital death. Shifting resuscitation from the hospital to the point of injury has shown great promise in decreasing mortality among the severely injured. MATERIALS AND METHODS: Our regional trauma network (Southwest Texas Regional Advisory Council) developed and implemented a multiphased approach toward facilitating remote damage control resuscitation. This approach required placing low-titer O+ whole blood (LTO+ WB) at helicopter emergency medical service bases, transitioning hospital-based trauma resuscitation from component therapy to the use of whole blood, modifying select ground-based units to carry and administer whole blood at the scene of an accident, and altering the practices of our blood bank to support our new initiative. In addition, we had to provide information and training to an entire large urban emergency medical system regarding changes in policy. RESULTS: Through a thorough, structured program we were able to successfully implement point-of-injury resuscitation with LTO+ WB. Preliminary evaluation of our first 25 patients has shown a marked decrease in mortality compared to our historic rate using component therapy or crystalloid solutions. Additionally, we have had zero transfusion reactions or seroconversions. CONCLUSION: Transfusion at the scene within minutes of injury has the potential to save lives. As our utilization expands to our outlying network we expect to see a continued decrease in mortality among significantly injured trauma patients.

Left atrial thrombi following tranexamic acid in a bleeding trauma patient-A word of caution.

We describe the case of a bleeding trauma patient who received tranexamic acid (TXA) during air transport who subsequently developed multiple intra-cardiac thrombi. The administration of TXA during transport may be associated with this unusual presentation.

Remote Damage Control Resuscitation in Austere Environments.

Hemorrhage is the leading cause of preventable military and civilian trauma death. Damage control resuscitation with concomitant mechanical hemorrhage control has become the preferred in-hospital treatment of hemorrhagic shock. In particular, plasma-based resuscitation with decreased volumes of crystalloids and artificial colloids as part of damage control resuscitation has improved outcomes in the military and civilian sectors. However, translation of these principles and techniques to the prehospital, remote, and austere environments, known as remote damage control resuscitation, is challenging given the resource limitations in these settings. Rapid administration of tranexamic acid and reconstituted freeze-dried (lyophilized) plasma as early as the point of injury are feasible and likely beneficial, but comparative studies in the literature are lacking. Whole blood is likely the best fluid therapy for traumatic hemorrhagic shock, but logistical hurdles need to be addressed. Rapid control of external hemorrhage with hemostatic dressings and extremity tourniquets are proven therapies, but control of noncompressible hemorrhage (ie, torso hemorrhage) remains a significant challenge.

Implications of humanitarian orthopaedic surgery in a combat zone: Operation Enduring Freedom and Iraqi Freedom experience.

The primary mission of deployed military orthopaedic surgeons in a combat zone is to treat musculoskeletal battlefield trauma and associated wartime injuries. The role of humanitarian surgical care during combat operations has not been defined. An anonymous online survey was sent to databases containing all U.S. military active-duty orthopaedic surgeons as well as to members of the Society of Military Orthopaedic Surgeons. Inclusion criteria for the study were defined as at least one deployment to Iraq (Operation Iraqi Freedom, OIF) or Afghanistan (Operation Enduring Freedom, OEF). Three hundred fifty-six invitations were sent with 107 orthopaedic surgeons completing the survey. Respondents reported approximately 3,000 humanitarian surgeries performed in the combat zone, with 70% to 80% involving chronic deformity and nonunion surgeries. Seventy-nine percent of the respondents believed that humanitarian surgery was a key component of the mission, improved skills (73%), benefited population (76%), and improved security (61%). A significant amount of humanitarian surgery in the combat zone has been performed in OEF/OIF.

Immediate Angiography and Decreased In-Hospital Mortality of Adult Trauma Patients: A Nationwide Study.

PURPOSE: This study aimed to elucidate whether immediate angiography within 30 min is associated with lower in-hospital mortality compared with non-immediate angiography. MATERIALS AND METHODS: We conducted a retrospective cohort study using a nationwide trauma databank (2019-2020). Adult trauma patients who underwent emergency angiography within 12 h after hospital arrival were included. Patients who underwent surgery before angiography were excluded. Immediate angiography was defined as one performed within 30 min after arrival (door-to-angio time ≤ 30 min). In-hospital mortality and non-operative management (NOM) failure were compared between patients with immediate and non-immediate angiography. Inverse probability weighting with propensity scores was conducted to adjust patient demographics, injury mechanism and severity, vital signs on hospital arrival, and resuscitative procedures. A restricted cubic spline curve was drawn to reveal survival benefits by door-to-angio time. RESULTS: Among 1,455 patients eligible for this study, 92 underwent immediate angiography. Angiography ≤ 30 min was associated with decreased in-hospital mortality (5.0% vs 11.1%; adjusted odds ratio [OR], 0.42 [95% CI, 0.31-0.56]; p < 0.001), as well as lower frequency of NOM failure: thoracotomy and laparotomy after angiography (0.8% vs. 1.8%; OR, 0.44 [0.22-0.89] and 2.6% vs. 6.5%; OR, 0.38 [0.26-0.56], respectively). The spline curve showed a linear association between increasing mortality and prolonged door-to-angio time in the initial 100 min after arrival. CONCLUSION: In trauma patients, immediate angiography ≤ 30 min was associated with lower in-hospital mortality and fewer NOM failures. LEVEL OF EVIDENCE: Level 3b, non randomized controlled cohort/follow up study.

Follow-up computed tomography and unexpected hemostasis in non-operative management of pediatric blunt liver and spleen injury.

PURPOSE: While follow-up CT and prophylactic embolization with angiography are often conducted during non-operative management (NOM) for BLSI, particularly in a high-grade injury, the utility of early repeated CT for preventing unexpected hemorrhage remains unclear. This study aimed to elucidate whether early follow-up computerized tomography (CT) within 7 days after admission would decrease unexpected hemostatic procedures on pediatric blunt liver and spleen injury (BLSI). METHODS: A post-hoc analysis of a multicenter observational cohort study on pediatric patients with BLSI (2008-2019) was conducted on those who underwent NOM, in whom the timing of follow-up CT were decided by treating physicians. The incidence of unexpected hemostatic procedure (laparotomy and/or emergency angiography for ruptured pseudoaneurysm) and complications related to BLSI were compared between patients with and without early follow-up CT within 7 days. Inverse probability weighting with propensity scores adjusted patient demographics, comorbidities, mechanism and severity of injury, initial resuscitation, and institutional characteristics. RESULTS: Among 1320 included patients, 552 underwent early follow-up CT. Approximately 25% of patients underwent angiography on the day of admission. The incidence of unexpected hemostasis was similar between patients with and without early repeat CT (8 [1.4%] vs. 6 [0.8%]; adjusted OR, 1.44 [0.62-3.34]; p = 0.40). Patients with repeat CT scans more frequently underwent multiple angiographies (OR, 2.79 [1.32-5.88]) and had more complications related to BLSI, particularly bile leak (OR, 1.73 [1.04-2.87]). CONCLUSION: Follow-up CT scans within 7 days was not associated with reduced unexpected hemostasis in NOM for pediatric BLSI.

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial.

Background: Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. Methods: We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. Results: NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (ß=-27.6, 95% CI (-51.3 to -3.9), p=0.02). Conclusions: Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. Level of evidence: Level II.

Prehospital tranexamic acid is associated with a survival benefit without an increase in complications: results of two harmonized randomized clinical trials.

INTRODUCTION: Recent randomized clinical trials have demonstrated that prehospital tranexamic acid (TXA) administration following injury is safe and improves survival. However, the effect of prehospital TXA on adverse events, transfusion requirements and any dose response relationships require further elucidation. METHODS: A secondary analysis was performed using harmonized data from two large, double-blinded, randomized prehospital TXA trials. Outcomes, including 28-day mortality, pertinent adverse events and 24-hour red cell transfusion requirements were compared between TXA and placebo groups. Regression analyses were utilized to determine the independent associations of TXA after adjusting for study enrollment, injury characteristics and shock severity across a broad spectrum of injured patients. Dose response relationships were similarly characterized based upon grams of prehospital TXA administered. RESULTS: A total of 1744 patients had data available for secondary analysis and were included in the current harmonized secondary analysis. The study cohort had an overall mortality of 11.2% and a median injury severity score of 16 (IQR: 5-26). TXA was independently associated with a lower risk of 28-day mortality (HR: 0.72, 95% CI 0.54, 0.96, p = 0.03). Prehospital TXA also demonstrated an independent 22% lower risk of mortality for every gram of prehospital TXA administered (HR: 0.78, 95% CI 0.63, 0.96, p = 0.02). Multivariable linear regression verified that patients who received TXA were independently associated with lower 24-hour red cell transfusion requirements (ß: -0.31, 95% CI -0.61, -0.01, p = 0.04) with a dose-response relationship (ß: -0.24, 95% CI -0.45, -0.02, p = 0.03). There was no independent association of prehospital TXA administration on VTE, seizure, or stroke. CONCLUSIONS: In this secondary analysis of harmonized data from two large randomized interventional trials, prehospital TXA administration across a broad spectrum of injured patients is safe. Prehospital TXA is associated with a significant 28-day survival benefit, lower red cell transfusion requirements at 24 hours and demonstrates a dose-response relationship. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Advancing Combat Casualty Care Statistics and Other Battlefield Care Metrics.

Aggregate statistics can provide intra-conflict and inter-conflict mortality comparisons and trends within and between U.S. combat operations. However, capturing individual-level data to evaluate medical and non-medical factors that influence combat casualty mortality has historically proven difficult. The Department of Defense (DoD) Trauma Registry, developed as an integral component of the Joint Trauma System during recent conflicts in Afghanistan and Iraq, has amassed individual-level data that have afforded greater opportunity for a variety of analyses and comparisons. Although aggregate statistics are easily calculated and commonly used across the DoD, other issues that require consideration include the impact of individual medical interventions, non-medical factors, non-battle-injured casualties, and incomplete or missing medical data, especially for prehospital care and forward surgical team care. Needed are novel methods to address these issues in order to provide a clearer interpretation of aggregate statistics and to highlight solutions that will ultimately increase survival and eliminate preventable death on the battlefield. Although many U.S. military combat fatalities sustain injuries deemed non-survivable, survival among these casualties might be improved using primary and secondary prevention strategies that prevent injury or reduce injury severity. The current commentary proposes adjustments to traditional aggregate combat casualty care statistics by integrating statistics from the DoD Military Trauma Mortality Review process as conducted by the Joint Trauma System and Armed Forces Medical Examiner System.

Characterization of adverse events in injured patients at risk of hemorrhagic shock: a secondary analysis of three harmonized prehospital randomized clinical trials.

Background: The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness. Methods: We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes. Results: We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ2=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as 'definitely not related' or 'probably not related' to the intervention. Conclusions: AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials. Trial registration numbers: NCT01818427, NCT02086500 and NCT03477006. Level of evidence: II.