The employment of resuscitative endovascular balloon occlusion of the aorta in deployed settings.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has been often used in place of open aortic occlusion for management of hemorrhagic shock in trauma. There is a paucity of data evaluating REBOA usage in military settings. STUDY DESIGN AND METHODS: We queried the Department of Defense Trauma Registry (DODTR) for all cases with at least one intervention or assessment available within the first 72 h after injury between 2007 and 2023. We used relevant procedural codes to identify the use of REBOA within the DODTR, and we used descriptive statistics to characterize its use. RESULTS: We identified 17 cases of REBOA placed in combat settings from 2017 to 2019. The majority of these were placed in the operating room (76%) and in civilian patients (70%). A penetrating mechanism caused the injury in 94% of cases with predominantly the abdomen and extremities having serious injuries. All patients subsequently underwent an exploratory laparotomy after REBOA placement, with moderate numbers of patients having spleen, liver, and small bowel injuries. The majority (82%) of included patients survived to hospital discharge. DISCUSSION: We describe 17 cases of REBOA within the DODTR from 2007 to 2023, adding to the limited documentation of patients undergoing REBOA in military settings. We identified patterns of injury in line with previous studies of patients undergoing REBOA in military settings. In this small sample of military casualties, we observed a high survival rate.

A prospective, pragmatic non-inferiority study of emergency intubation success with the single-use i-view versus standard reusable video laryngoscope.

INTRODUCTION: Video laryngoscope (VL) technology improves first-pass success. The novel i-view VL device is inexpensive and disposable. We sought to determine the first-pass intubation success with the i-view VL device versus the standard reusable VL systems in routine use at each site. METHODS: We performed a prospective, pragmatic study at two major emergency departments (EDs) when VL was used. We rotated i-view versus reusable VL as the preferred device of the month based on an a priori schedule. An investigator-initiated interim analysis was performed. Our primary outcome was a first-pass success with a non-inferiority margin of 10% based on the per-protocol analysis. RESULTS: There were 93 intubations using the reusable VL devices and 81 intubations using the i-view. Our study was stopped early due to futility in reaching our predetermined non-inferiority margin. Operator and patient characteristics were similar between the two groups. The first-pass success rate for the i-view group was 69.1% compared to 84.3% for the reusable VL group. A non-inferiority analysis indicated that the difference (-15.1%) and corresponding 90% confidence limits (-25.3% to -5.0%) did not fall within the predetermined 10% non-inferiority margin. CONCLUSIONS: The i-view device failed to meet our predetermined non-inferiority margin when compared to the reusable VL systems with the study stopping early due to futility. Significant crossover occurred at the discretion of the intubating operator during the i-view month.

Association of freeze-dried plasma with 24-h mortality among trauma patients at risk for hemorrhage.

BACKGROUND: Blood products form the cornerstone of contemporary hemorrhage control but are limited resources. Freeze-dried plasma (FDP), which contains coagulation factors, is a promising adjunct in hemostatic resuscitation. We explore the association between FDP alone or in combination with other blood products on 24-h mortality. STUDY DESIGN AND METHODS: This is a secondary data analysis from a cross-sectional prospective observational multicenter study of adult trauma patients in the Western Cape of South Africa. We compare mortality among trauma patients at risk of hemorrhage in three treatment groups: Blood Products only, FDP + Blood Products, and FDP only. We apply inverse probability of treatment weighting and fit a multivariable Cox proportional hazards model to assess the hazard of 24-h mortality. RESULTS: Four hundred and forty-eight patients were included, and 55 (12.2%) died within 24 h of hospital arrival. Compared to the Blood Products only group, we found no difference in 24-h mortality for the FDP + Blood Product group (p = .40) and a lower hazard of death for the FDP only group (hazard = 0.38; 95% CI, 0.15-1.00; p = .05). However, sensitivity analyses showed no difference in 24-h mortality across treatments in subgroups with moderate and severe shock, early blood product administration, and accounting for immortal time bias. CONCLUSION: We found insufficient evidence to conclude there is a difference in relative 24-h mortality among trauma patients at risk for hemorrhage who received FDP alone, blood products alone, or blood products with FDP. There may be an adjunctive role for FDP in hemorrhagic shock resuscitation in settings with significantly restricted access to blood products.

Association of Prehospital Neck Wound Survivability and Battlefield Medical Evacuation Time in Afghanistan.

INTRODUCTION: The U.S. Military's Golden Hour policy led to improved warfighter survivability during the Global War on Terror. The policy's success is well-documented, but a categorical evaluation and stratification of medical evacuation (MEDEVAC) times based on combat injury is lacking. METHODS: We queried the Department of Defense Joint Trauma System Prehospital Trauma Registry for casualties with documented penetrating neck trauma in Afghanistan requiring battlefield MEDEVAC from June 15, 2009, through February 1, 2021. Casualties were excluded if the time from the point of injury to reach higher level medical care was not documented, listed as zero, or exceeded 4 hours. They were also excluded if demographic data were incomplete or deemed unreliable or if their injuries occurred outside of Afghanistan.We designed a logistic regression model to test for associations in survivability, adjusting for composite injury severity score, patient age group, and type of next higher level of care reached. We then used our model to interpolate MEDEVAC times associated with 0.1%, 1%, and 10% increased risk of death for an incapacitated casualty with penetrating neck trauma. RESULTS: Of 1,147 encounters, 444 casualties met inclusion criteria. Of these casualties, 430 (96.9%) survived to discharge. Interpolative analysis of our multivariable logistic regression model showed that MEDEVAC times ≥8 minutes, ≥53 minutes, and ≥196 minutes are associated with a 0.1%, 1%, and 10% increased risk of mortality from baseline, respectively. CONCLUSIONS: Our data characterize the maximum MEDEVAC times associated with 0.1%, 1%, and 10% increased risk of death from baseline survivability for penetrating battlefield neck trauma in Afghanistan.

Intramuscular Administration of Tranexamic Acid in a Large Swine Model of Hemorrhage with Hyperfibrinolysis.

BACKGROUND: Traumatic injury with subsequent hemorrhage is one of the leading causes of mortality among military personnel and civilians alike. Post traumatic hemorrhage accounts for 40-50% of deaths in severe trauma patients occurring secondary to direct vessel injury or the development of trauma induced coagulopathy (TIC). Hyperfibrinolysis plays a major role in TIC and its presence increases a patient's risk of mortality. Early therapeutic intervention with intravenous (IV) tranexamic acid (TXA) prevents development of hyperfibrinolysis and subsequent TIC leading to decreased mortality. However, obtaining IV access in an austere environment can be challenging. In this study, we evaluated the efficacy of intramuscular (IM) versus IV TXA at preventing hyperfibrinolysis in a hemorrhaged swine. METHODS: Yorkshire cross swine were randomized on the day of study to receive IM or IV TXA or no treatment. Swine were sedated, intubated, and determined to be hemodynamically stable prior to experimentation. Controlled hemorrhaged was induced by the removal of 30% total blood volume. After hemorrhage, swine were treated with 1000 mg of IM or IV TXA. Control animals received no treatment. Thirty minutes post TXA treatment, fibrinolysis was induced with a 50 mg bolus of tissue plasminogen activator (tPA). Blood samples were collected to evaluate blood TXA concentrations, blood gases, blood chemistry, and fibrinolysis. RESULTS: Blood TXA concentrations were significantly different between administration routes at the early timepoints, but were equivalent by 20 minutes after injection, remaining consistently elevated for up to three hours post administration. Induction of fibrinolysis resulted in 87.18 ± 4.63% lysis in control animals, compared to swine treated with IM TXA 1.96 ± 2.66 % and 1.5 ± 0.42% lysis in the IV TXA group. CONCLUSION: In the large swine model of hemorrhage with hyperfibrinolysis, IM TXA is bioequivalent and equally efficacious in preventing hyperfibrinolysis as IV TXA administration.

Seasonal Association With Hypothermia in Combat Trauma.

INTRODUCTION: Hypothermia increases mortality in trauma populations and frequently occurs in military casualties due to the nature of combat environments. The association between hypothermia and the time of year when injured remains unclear. We sought to determine the association between seasonal changes in temperature and hypothermia among combat casualties. MATERIALS AND METHODS: This observational study was a secondary analysis of a previously described Department of Defense Trauma Registry dataset which included U.S. military and Coalition casualties who received prehospital care from January 2007 to March 2020 in Afghanistan and Iraq. We tested for associations between hypothermia (<36.2°C) and seasonal ambient temperatures by constructing multivariable logistic regression models. Summer was defined as June through August and winter as December through February. We assumed that the combat operations occurred in the area near the point of first contact with the deployed military treatment facilities. This study was determined to be exempt from Institutional Review Board oversight. RESULTS: There were 5,821 that met inclusion for this study. Within the multivariable logistic regression model, we adjusted for injury severity score, mechanism of injury, and imputed transport time, finding that combat casualties were 2.28 (odds ratio, 95% confidence interval 1.93-2.69) times more likely to develop hypothermia in the winter versus summer. When using temperature as a continuous outcome, casualties had a lower emergency department temperature during the winter (parameter estimate -0.133°C, P < 0.001) after adjusting for confounders. In casualties experiencing hypothermia, mortality was higher (4% versus 1%, P < 0.001), and composite median injury severity score values were higher (10 versus 5, P < 0.001). Among hypothermic casualties, serious injuries were significantly more common (all P < 0.001) to the head (15% versus 7%), thorax (15% versus 7%), abdomen (9% versus 6%), extremities (35% versus 22%), and skin (4% versus 2%). CONCLUSIONS: We found a seasonal variation in the occurrence of hypothermia in a large cohort of trauma casualties. Despite adjustment for multiple known confounders, our findings substantiate probable ambient temperature variations to trauma-induced hypothermia. Furthermore, our findings, when taken in the context of other studies on the efficacy of current hypothermia prevention and treatment strategies, support the need for better methods to mitigate hypothermia in future cold-weather operations.

Application Times, Placement Accuracy, and User Ratings of Commercially Available Manual and Battery-Powered Intraosseous Catheters in a High Bone Density Cadaveric Swine Model.

INTRODUCTION: Intraosseous (IO) infusion, the pressurized injection of fluids into bone through a catheter, is a life-preserving resuscitative technique for treating trauma patients with severe hemorrhage. However, little is known regarding the application times, placement accuracy, and end-user ratings of battery-powered and manual IO access devices. This study was specifically designed to fill these knowledge gaps on six FDA-approved IO access devices. MATERIALS AND METHODS: Three experienced U.S. Navy Emergency Medicine residents each placed commercially available 15-gauge IO catheters in cadaveric swine (Sus scrofa) proximal humeri and sternums in a randomized prospective experimental design. Devices included the battery-powered EZ-IO Rapid Infuser and the manual Jamshidi IO, PerSys NIO, SAM Manual IO, Tactical Advanced Lifesaving IO Needle (TALON), and PYNG First Access for Shock and Trauma 1 (30 trials per device, 10 per user, 210 total trials). Application times, placement accuracy in medullary (zone 1) and trabecular (zone 2) bone while avoiding cortical (zone 3) bone, and eight subjective user ratings were analyzed using ANOVA and nonparametric statistics at P < .05. RESULTS: The EZ-IO demonstrated the fastest application times, high rates in avoiding zone 3, and the highest user ratings (P < .0001). The TALON conferred intermediate placement times, highest rates of avoiding zone 3, and second-highest user ratings. The SAM Manual IO and Jamshidi performed poorly, with mixed results for the PerSys NIO and PYNG First Access for Shock and Trauma 1. CONCLUSIONS: The battery-powered EZ-IO performed best and remains the IO access device of choice. The present findings suggest that the TALON should be considered as a manual backup to the EZ-IO.

Concurrent determination of cyanide and thiocyanate in human and swine antemortem and postmortem blood by high-performance liquid chromatography-tandem mass spectrometry.

Cyanide (in the form of cyanide anion (CN-) or hydrogen cyanide (HCN), inclusively represented as CN) can be a rapidly acting and deadly poison, but it is also a common chemical component of a variety of natural and anthropogenic substances. The main mechanism of acute CN toxicity is based on blocking terminal electron transfer by inhibiting cytochrome c oxidase, resulting in cellular hypoxia, cytotoxic anoxia, and potential death. Due to the well-established link between blood CN concentrations and the manifestation of symptoms, the determination of blood concentration of CN, along with the major metabolite, thiocyanate (SCN-), is critical. Because currently there is no method of analysis available for the simultaneous detection of CN and SCN- from blood, a sensitive method for the simultaneous analysis of CN and SCN- from human ante- and postmortem blood via liquid chromatography-tandem MS analysis was developed. For this method, sample preparation for CN involved active microdiffusion with subsequent chemical modification using naphthalene-2,3-dicarboxaldehyde (NDA) and taurine (i.e., the capture solution). Preparation for SCN- was accomplished via protein precipitation and monobromobimane (MBB) modification. The method produced good sensitivity for CN with antemortem limit of detection (LODs) of 219 nM and 605 nM for CN and SCN-, respectively, and postmortem LODs of 352 nM and 509 nM. The dynamic ranges of the method were 5-500 µM and 10-500 µM in ante- and postmortem blood, respectively. In addition, the method produced good accuracy (100 ± 15%) and precision (≤ 15.2% relative standard deviation). The method was able to detect elevated levels of CN and SCN- in both antemortem (N = 5) and postmortem (N = 4) blood samples from CN-exposed swine compared to nonexposed swine.

A Descriptive Study of Casualties Evacuated Out of Afghanistan by Critical Care Air Transport Teams During the Withdrawal of U.S. Troops.

INTRODUCTION: The War in Afghanistan ended in August 2021. Evacuation from the country was a large effort during the last days of the conflict. During evacuation efforts at Kabul Hamid Karzai International Airport, a suicide bombing occurred necessitating emergent medical care for many injured troops and civilians. The U.S. Air Force Critical Care Air Transport Teams (CCATTs) played a role in the medical care provided during the operations in Afghanistan. We report on in-flight events and interventions that took place during the final days of the Afghanistan withdrawal. MATERIALS AND METHODS: We performed a retrospective chart review of patients requiring aeromedical evacuation from the Afghanistan theater of operations by CCATT from July 1 to August 30, 2021. From the CCATT patient care record, data abstractors collected patient characteristics, flight information, vital signs, laboratory values, in-flight interventions, and in-flight events in a study-specific electronic database. We performed descriptive analyses of patient characteristics and in-flight interventions. This study was approved by the San Antonio Institutional Review Board. RESULTS: Nine patients were included in this analysis. Seven out of nine patients were foreign nationals; the remaining two were U.S. Marines. Five patients suffered penetrating injuries from gunshot wounds and four suffered blast injuries. Six received intravenous narcotic analgesia. Four received intravenous sedatives, and four received antibiotics in flight. Two patients required chest tube management. One patient received blood. Three patients were in acute respiratory distress. CONCLUSIONS: Severe injuries were sustained during the withdrawal efforts at the end of the War in Afghanistan. Critical Care Air Transport Teams played a role in the care and evacuation of patients out of theater during this unique and unprecedented time. Even given the limitations associated with retrospective studies and a small sample size, information reported in this study can help inform future decisions, and aid in preparatory efforts for future operations, that may require medical care by CCATT.

Market Analysis of Video Laryngoscopy Equipment for the Role 1 Setting.

INTRODUCTION: Airway compromise is the second leading cause of potentially preventable prehospital combat death. Endotracheal intubation (ETI) remains the most common role 1 airway intervention. Video laryngoscopy (VL) is superior to direct laryngoscopy (DL) for first-attempt intubation, especially in less-experienced providers and for trauma patients. The cost has been a major challenge in pushing VL technology far-forward; however, the cost of equipment continues to become more affordable. We conducted a market analysis of VL devices under $10,000 for possible options for role 1. MATERIALS AND METHODS: We searched Google, PubMed, and the Food and Drug Administration database from August 2022 to January 2023 with a combination of several keywords to identify current VL market options under $10,000. After identifying relevant manufacturers, we then reviewed individual manufacturer or distributor websites for pricing data and system specifications. We noted several characteristics regarding VL device design for comparison. These include monitor features, size, modularity, system durability, battery life, and reusability. When necessary, we requested formal price quotes from respective companies. RESULTS: We identified 17 VL options under $10,000 available for purchase, 14 of which were priced below $5,000 for individual units. Infium (n = 3) and Vimed Medical (n = 4) provided the largest number of unique models. VL options under $10,000 exist in both reusable and disposable modalities. These modalities included separate monitors as well as monitors attached to the VL handle. Disposable options, on a per-unit basis, cost less than reusable options. CONCLUSIONS: Several VL options exist within our goal price point in both reusable and disposable options. Clinical studies assessing the technology performance of ETI and deliberate downselection are needed to identify the most cost-effective solution for role 1 dispersion.

Feasibility of conducting a military-relevant multicenter cohort study to assess outcomes of early trauma resuscitative interventions in a prolonged care civilian setting.

BACKGROUND: The Epidemiology and Outcomes of Prolonged Trauma Care (EpiC) study is a 4-year, prospective, observational, large-scale epidemiologic study in South Africa. It will provide novel evidence on how early resuscitation impacts postinjury mortality and morbidity in patients experiencing prolonged care. A pilot study was performed to inform the main EpiC study. We assess outcomes and experiences from the pilot to evaluate overall feasibility of conducting the main EpiC study. METHODS: The pilot was a prospective, multicenter, cohort study at four ambulance bases, four hospitals, and two mortuaries from March 25 to August 27, 2021. Trauma patients 18 years or older were included. Data were manually collected via chart review and abstraction from clinical records at all research sites and inputted into Research Electronic Data Capture. Feasibility metrics calculated were as follows: screening efficiency, adequate enrollment, availability of key exposure and outcome data, and availability of injury event date/time. RESULTS: A total of 2,303 patients were screened. Of the 981 included, 70% were male, and the median age was 31.4 years. Six percent had one or more trauma relevant comorbidity. Fifty-five percent arrived by ambulance. Forty percent had penetrating injuries. Fifty-three percent were critically injured. Thirty-three percent had one or more critical interventions performed. Mortality was 5%. Four of the eight feasibility metrics exceed the predetermined threshold: screening ratio, monthly enrollment, percentage with significant organ failure, and missing injury date/time for emergency medical services patients. Two feasibility metrics were borderline: key exposure and primary outcome. Two feasibility metrics fell below the feasibility threshold, which necessitate changes to the main EpiC study: percentage with infections and missing injury date/time for walk-in patients. CONCLUSION: The EpiC pilot study suggests that the main EpiC study is overall feasible. Improved data collection for infections and methods for missing data will be developed for the main study. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level V.

Improving prehospital traumatic shock care: implementation and clinical effectiveness of a pragmatic, quasi-experimental trial in a resource-constrained South African setting.

OBJECTIVES: This project seeks to improve providers' practices and patient outcomes from prehospital (ie, ambulance-based) trauma care in a middle-income country using a novel implementation strategy to introduce a bundled clinical intervention. DESIGN: We conduct a two-arm, controlled, mixed-methods, hybrid type II study. SETTING: This study was conducted in the Western Cape Government Emergency Medical Services (EMS) system of South Africa. INTERVENTIONS: We pragmatically implemented a simplified prehospital bundle of trauma care (with five core elements) using a novel workplace-based, peer-to-peer, rapid training format. We assigned the intervention and control sites. OUTCOME MEASURES: We assessed implementation effectiveness among EMS providers and stakeholders, using the RE-AIM framework. Clinical effectiveness was assessed at the patient level, using changes in Shock Index x Age (SIxAge). Indices and cut-offs were established a priori. We performed a difference-in-differences (D-I-D) analysis with a multivariable mixed effects model. RESULTS: 198 of 240 (82.5%) EMS providers participated, 93 (47%) intervention and 105 (53%) control, with similar baseline characteristics. The overall implementation effectiveness was excellent (80.6%): reach was good (65%), effectiveness was excellent (87%), implementation fidelity was good (72%) and adoption was excellent (87%). Participants and stakeholders generally reported very high satisfaction with the implementation strategy citing that it was a strong operational fit and effective educational model for their organisation. A total of 770 patients were included: 329 (42.7%) interventions and 441 (57.3%) controls, with no baseline differences. Intervention arm patients had more improved SIxAge compared with control at 4 months, which was not statistically significant (-1.4 D-I-D; p=0.35). There was no significant difference in change of SIxAge over time between the groups for any of the other time intervals (p=0.99). CONCLUSIONS: In this quasi-experimental trial of bundled care using the novel workplace rapid training approach, we found overall excellent implementation effectiveness but no overall statistically significant clinical effectiveness.

Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory in mice and is neuroprotective in pigs.

The Ca2+/calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses a problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological CaMKII inhibition with the neuroprotective peptide tatCN19o interfered with learning in mice only mildly and transiently (for less than 1 h) and did not at all reverse pre-formed memories. These results were obtained with ≥500-fold of the dose that protected hippocampal neurons from cell death after a highly clinically relevant pig model of transient global cerebral ischemia: ventricular fibrillation followed by advanced life support and electrical defibrillation to induce the return of spontaneous circulation. Of additional importance for therapy development, our preliminary cardiovascular safety studies in mice and pig did not indicate any concerns with acute tatCN19o injection. Taken together, although prolonged interference with CaMKII signaling can erase memory, acute short-term CaMKII inhibition with tatCN19o did not cause such retrograde amnesia that would pose a contraindication for therapy.

Hyperoxia is associated with a greater risk for mortality in critically ill traumatic brain injury patients than in critically ill trauma patients without brain injury.

OBJECTIVE: The role of hyperoxia in patients with traumatic brain injury (TBI) remains controversial. The objective of this study was to determine the association between hyperoxia and mortality in critically ill TBI patients compared to critically ill trauma patients without TBI. DESIGN: Secondary analysis of a multicenter retrospective cohort study. SETTING: Three regional trauma centers in Colorado, USA, between October 1, 2015, and June 30, 2018. PATIENTS: We included 3464 critically injured adults who were admitted to an intensive care unit (ICU) within 24 h of arrival and qualified for inclusion into the state trauma registry. We analyzed all available SpO2 values during the first seven ICU days. The primary outcome was in-hospital mortality. Secondary outcomes included the proportion of time spent in hyperoxia (defined as SpO2 > 96%) and ventilator-free days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: In-hospital mortality occurred in 163 patients (10.7%) in the TBI group and 101 patients (5.2%) in the non-TBI group. After adjusting for ICU length of stay, TBI patients spent a significantly greater amount of time in hyperoxia versus non-TBI patients (p = 0.024). TBI status significantly modified the effect of hyperoxia on mortality. At each specific SpO2 level, the risk of mortality increases with increasing FiO2 for both patients with and without TBI. This trend was more pronounced at lower FiO2 and higher SpO2 values, where a greater number of patient observations were obtained. Among patients who required invasive mechanical ventilation, TBI patients required significantly more days of ventilation to day 28 than non-TBI patients. CONCLUSIONS: Critically ill trauma patients with a TBI spend a greater proportion of time in hyperoxia compared to those without a TBI. TBI status significantly modified the effect of hyperoxia on mortality. Prospective clinical trials are needed to better assess a possible causal relationship.

Trends in Traumatic Brain Injury Among U.S. Service Members Deployed in Iraq and Afghanistan, 2002-2016.

INTRODUCTION: Traumatic brain injury (TBI) is a major health issue for service members deployed and is more common in recent conflicts; however, a thorough understanding of risk factors and trends is not well described. This study aims to characterize the epidemiology of TBI in U.S. service members and the potential impacts of changes in policy, care, equipment, and tactics over the 15 years studied. METHODS: Retrospective analysis of U.S. Department of Defense Trauma Registry data (2002-2016) was performed on service members treated for TBI at Role 3 medical treatment facilities in Iraq and Afghanistan. Risk factors and trends in TBI were examined in 2021 using Joinpoint regression and logistic regression. RESULTS: Nearly one third of 29,735 injured service members (32.4%) reaching Role 3 medical treatment facilities had TBI. The majority sustained mild (75.8%), followed by moderate (11.6%) and severe (10.6%) TBI. TBI proportion was higher in males than in females (32.6% vs 25.3%; p<0.001), in Afghanistan than in Iraq (43.8% vs 25.5%; p<0.001), and in battle than in nonbattle (38.6% vs 21.9%; p<0.001). Patients with moderate or severe TBI were more likely to have polytrauma (p<0.001). TBI proportion increased over time, primarily in mild TBI (p=0.02), slightly in moderate TBI (p=0.04), and most rapidly between 2005 and 2011, with a 2.48% annual increase. CONCLUSIONS: One third of injured service members at Role 3 medical treatment facilities experienced TBI. Findings suggest that additional preventive measures may decrease TBI frequency and severity. Clinical guidelines for field management of mild TBI may reduce the burden on evacuation and hospital systems. Additional capabilities may be needed for military field hospitals.

Short-term CaMKII inhibition with tatCN19o does not erase pre-formed memory and is neuroprotective in non-rodents.

The Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) is a central regulator of learning and memory, which poses a problem for targeting it therapeutically. Indeed, our study supports prior conclusions that long-term interference with CaMKII signaling can erase pre-formed memories. By contrast, short-term pharmacological CaMKII inhibition with tatCN19o interfered with learning in mice only mildly and transiently (for less than 1 h) and did not at all reverse pre-formed memories. This was at ≥500fold of the dose that protected hippocampal neurons from cell death after a highly clinically relevant pig model of transient global cerebral ischemia: ventricular fibrillation followed by advanced life support and electrical defibrillation to induce return of spontaneous circulation. Of additional importance for therapeutic development, cardiovascular safety studies in mice and pig did not indicate any concerns with acute tatCN19o injection. Taken together, even though prolonged interference with CaMKII signaling can erase memory, acute short-term CaMKII inhibition with tatCN19o did not cause such retrograde amnesia that would pose a contraindication for therapy.

Prehospital Pharmacotherapy in Moderate and Severe Traumatic Brain Injury: A Systematic Review.

BACKGROUND: Traumatic brain injury (TBI) affects civilian and military populations with high morbidity and mortality rates and devastating sequelae. As the US military shifts its operational paradigm to prepare for future large-scale combat operations, the need for prolonged casualty care is expected to intensify. Identifying efficacious prehospital TBI management strategies is therefore vital. Numerous pharmacotherapies are beneficial in the inpatient management of TBI, including beta blockers, calcium channel blockers, statins, and other agents. However, their utility in prehospital management of moderate or severe TBI is not well understood. We performed a systematic review to elucidate agents of potential prehospital benefit in moderate and severe TBI. METHODS: We searched 6 databases from January 2000 through December 2021 without limitations in outcome metrics using a variety of search terms designed to encapsulate all studies pertaining to prehospital TBI management. We identified 2,142 unique articles, which netted 114 studies for full review. Seven studies met stringent inclusion criteria for our aims. RESULTS: Studies meeting inclusion criteria assessed tranexamic acid (TXA) (n=6) and ethanol (n=1). Of the TXA studies, 3 were randomized controlled trials, 2 were retrospective cohort studies, 1 was a prospective cohort study, and 1 was a meta-analysis. Notably absent were papers investigating therapeutics shown to be beneficial in inpatient hospital treatment of TBI. Overall, data suggest TXA administration is potentially beneficial in moderate or severe TBI with or without intracranial hemorrhage. Severe TBI with or without penetrating trauma was associated with worse overall outcomes, regardless of TXA use. CONCLUSION: Effective interventions for treating moderate or severe TBI are lacking. TXA is the most widely studied pharmacologic intervention and appears to offer some benefit without adverse effects in moderate TBI (with or without intracranial hemorrhage) in the pre-hospital setting despite heterogeneous results. Limitations of these studies include heterogeneity in outcome metrics, patient populations, and circumstances of TXA use. We identified a gap in the literature in translating agents with demonstrated inpatient benefit to the prehospital setting. Further investigation into these and other novel therapeutic options in the prehospital arena is crucial to improving clinical outcomes in TBI.

Clinical Assessment of Low Calcium In traUMa (CALCIUM).

Major trauma frequently occurs in the deployed, combat setting and is especially applicable in the recent conflicts with explosives dominating the combat wounded. In future near-peer conflicts, we will likely face even more profound weapons including mortars and artillery. As such, the number of severely wounded will likely increase. Hypocalcemia frequently occurs after blood transfusions, secondary to the preservatives in the blood products; however, recent data suggests major trauma in and of itself is a risk factor for hypocalcemia. Calcium is a major ion involved in heart contractility; thus, hypocalcemia can lead to poor contractility. Smaller studies have linked hypocalcemia to worse outcomes, but it remains unclear what causes hypocalcemia and if intervening could potentially save lives. The objective of this study is to determine the incidence of hypocalcemia on hospital arrival and the association with survival. We are seeking to address the following scientific questions, (1) Is hypocalcemia present following traumatic injury prior to transfusion during resuscitation? (2) Does hypocalcemia influence the amount of blood products transfused? (3) To what extent is hypocalcemia further exacerbated by transfusion? (4) What is the relationship between hypocalcemia following traumatic injury and mortality? We will conduct a multicenter, prospective, observational study. We will gather ionized calcium levels at 0, 3, 6, 12, 18, and 24 hours as part of scheduled calcium measurements. This will ensure we have accurate data to assess the early and late effects of hypocalcemia throughout the course of resuscitation and hemorrhage control. These data will be captured by a trained study team at every site. Our findings will inform clinical practice guidelines and optimize the care delivered in the combat and civilian trauma setting. We are seeking 391 patients with complete data to meet our a priori inclusion criteria. Our study will have major immediate short-term findings including risk prediction modeling to assess who is at risk for hypocalcemia, data assessing interventions associated with the incidence of hypocalcemia, and outcome data including mortality and its link to early hypocalcemia.