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

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

Direct Trauma Center Access by Helicopter Emergency Medical Services is Associated With Improved Survival After Severe Injury.

OBJECTIVE: Evaluate the association of survival with helicopter transport directly to a trauma center compared with ground transport to a non-trauma center (NTC) and subsequent transfer. SUMMARY BACKGROUND DATA: Helicopter transport improves survival after injury. One potential mechanism is direct transport to a trauma center when the patient would otherwise be transported to an NTC for subsequent transfer. METHODS: Scene patients 16 years and above with positive physiological or anatomic triage criteria within PTOS 2000-2017 were included. Patients transported directly to level I/II trauma centers by helicopter were compared with patients initially transported to an NTC by ground with a subsequent helicopter transfer to a level I/II trauma center. Propensity score matching was used to evaluate the association between direct helicopter transport and survival. Individual triage criteria were evaluated to identify patients most likely to benefit from direct helicopter transport. RESULTS: In all, 36,830 patients were included. Direct helicopter transport was associated with a nearly 2-fold increase in odds of survival compared with NTC ground transport and subsequent transfer by helicopter (aOR 2.78; 95% CI 2.24-3.44, P <0.01). Triage criteria identifying patients with a survival benefit from direct helicopter transport included GCS≤13 (1.71; 1.22-2.41, P <0.01), hypotension (2.56; 1.39-4.71, P <0.01), abnormal respiratory rate (2.30; 1.36-3.89, P <0.01), paralysis (8.01; 2.03-31.69, P <0.01), hemothorax/pneumothorax (2.34; 1.36-4.05, P <0.01), and multisystem trauma (2.29; 1.08-4.84, P =0.03). CONCLUSIONS: Direct trauma center access is a mechanism driving the survival benefit of helicopter transport. First responders should consider helicopter transport for patients meeting these criteria who would otherwise be transported to an NTC.

Inner Deliberations of Surgeons Treating Critically-ill Emergency General Surgery Patients: A Qualitative Analysis.

BACKGROUND: 30% of elderly patients who require emergency general surgery (EGS) die in the year after the operation. Preoperative discussions can determine whether patients receive preference-sensitive care. Theoretically, surgeons frame their conversations after systematically assessing the risks and benefits of management options based on the clinical characteristics of each case. However, little is known about how surgeons actually deliberate about those options. OBJECTIVE: To identify variables that influence surgeons' assessment of management options for critically-ill EGS patients. METHODS: We conducted semi-structured interviews with 40 general surgeons in western Pennsylvania who worked in a variety of hospital settings. Interviews explored perioperative decision-making by asking surgeons to think aloud about selected memorable cases and a standardized case vignette of a frail patient with acute mesenteric ischemia. We used constant comparative methods to analyze interview transcripts and inductively developed a framework for the decision-making process. RESULTS: Surgeons averaged 13 years (standard deviation (SD) 10.4) of experience; 40% specialized in trauma/acute care surgery. Important themes regarding the main topic of "perioperative decision-making" included many considerations beyond the clinical characteristics of cases. Surgeons described the importance of variables ranging from the availability of institutional resources to professional norms. Surgeons often remarked on their desire to achieve individual flow, team efficiency, and concordant expectations of treatment and prognosis with patients. CONCLUSIONS: This is the first study to explore how surgeons decide among management options for critically-ill EGS patients. Surgeons' decision-making reflected a broad array of clinical, personal, and institutional variables. Effective interventions to ensure preference-sensitive care for EGS patients must address all of these variables.

Prehospital Blood Product and Crystalloid Resuscitation in the Severely Injured Patient: A Secondary Analysis of the Prehospital Air Medical Plasma Trial.

OBJECTIVE: The aim of this study was to determine whether prehospital blood products reduce 30-day mortality in patients at risk for hemorrhagic shock compared with crystalloid only resuscitation. SUMMARY OF BACKGROUND DATA: Hemorrhage is the primary cause of preventable death after injury. Large volume crystalloid resuscitation can be deleterious. The benefits of prehospital packed red blood cells (PRBCs), plasma, or transfusion of both products among trauma patients is unknown compared with crystalloid. METHODS: Secondary analysis of the multicenter PAMPer trial was performed on hypotensive injured patients from the scene. The trial randomized 27 helicopter bases to prehospital plasma or standard resuscitation. Standard resuscitation at the sites was equally divided between crystalloid and crystalloid + PRBC. This led to 4 prehospital resuscitation groups: crystalloid only; PRBC; plasma; and PRBC+plasma. Cox regression determined the association between resuscitation groups and risk-adjusted 30-day mortality. The dose effect of resuscitation fluids was also explored. RESULTS: Four hundred seven patients were included. PRBC+plasma had the greatest benefit [hazard ratio (HR) 0.38; 95% confidence interval (95% CI) 0.26-0.55, P < 0.001], followed by plasma (HR 0.57; 95% CI 0.36-0.91, P = 0.017) and PRBC (HR 0.68; 95% CI 0.49-0.95, P = 0.025) versus crystalloid only. Mortality was lower per-unit of PRBC (HR 0.69; 95% CI 0.52-0.92, p = 0.009) and plasma (HR 0.68; 95% CI 0.54-0.88, P = 0.003). Crystalloid volume was associated with increased mortality among patients receiving blood products (HR 1.65; 95% CI 1.17-2.32, P = 0.004). CONCLUSION: Patients receiving prehospital PRBC+plasma had the greatest mortality benefit. Crystalloid only had the worst survival. Patients with hemorrhagic shock should receive prehospital blood products when available, preferably PRBC+plasma. Prehospital whole blood may be ideal in this population.

Prehospital Plasma during Air Medical Transport in Trauma Patients at Risk for Hemorrhagic Shock.

BACKGROUND: After a person has been injured, prehospital administration of plasma in addition to the initiation of standard resuscitation procedures in the prehospital environment may reduce the risk of downstream complications from hemorrhage and shock. Data from large clinical trials are lacking to show either the efficacy or the risks associated with plasma transfusion in the prehospital setting. METHODS: To determine the efficacy and safety of prehospital administration of thawed plasma in injured patients who are at risk for hemorrhagic shock, we conducted a pragmatic, multicenter, cluster-randomized, phase 3 superiority trial that compared the administration of thawed plasma with standard-care resuscitation during air medical transport. The primary outcome was mortality at 30 days. RESULTS: A total of 501 patients were evaluated: 230 patients received plasma (plasma group) and 271 received standard-care resuscitation (standard-care group). Mortality at 30 days was significantly lower in the plasma group than in the standard-care group (23.2% vs. 33.0%; difference, -9.8 percentage points; 95% confidence interval, -18.6 to -1.0%; P=0.03). A similar treatment effect was observed across nine prespecified subgroups (heterogeneity chi-square test, 12.21; P=0.79). Kaplan-Meier curves showed an early separation of the two treatment groups that began 3 hours after randomization and persisted until 30 days after randomization (log-rank chi-square test, 5.70; P=0.02). The median prothrombin-time ratio was lower in the plasma group than in the standard-care group (1.2 [interquartile range, 1.1 to 1.4] vs. 1.3 [interquartile range, 1.1 to 1.6], P<0.001) after the patients' arrival at the trauma center. No significant differences between the two groups were noted with respect to multiorgan failure, acute lung injury-acute respiratory distress syndrome, nosocomial infections, or allergic or transfusion-related reactions. CONCLUSIONS: In injured patients at risk for hemorrhagic shock, the prehospital administration of thawed plasma was safe and resulted in lower 30-day mortality and a lower median prothrombin-time ratio than standard-care resuscitation. (Funded by the U.S. Army Medical Research and Materiel Command; PAMPer ClinicalTrials.gov number, NCT01818427 .).

The Whole is Greater Than the Sum of its Parts: GCS Versus GCS-Motor for Triage in Geriatric Trauma.

BACKGROUND: Trauma field triage matches injured patients to the appropriate level of care. Prior work suggests the Glasgow Coma Scale motor (GCSm) is as accurate as the total GCS (GCSt) and easier to use. However, older patients present with higher GCS for a given injury, and as such, it is unclear if this substitution is advisable. Our objective was to compare the GCS deficit patterns between geriatric and adult patients presenting with severe traumatic brain injury (TBI), as well as the diagnostic performance of the GCSm versus GCSt within the field triage criteria in these populations. MATERIALS AND METHODS: We conducted a retrospective, observational cohort study of patients ≥16 y in the National Trauma Data Bank 2007-2015. GCS deficit patterns were compared between adults (16-65) and geriatric patients (>65). Measures of diagnostic performance of GCSt≤13 versus GCSm≤5 criteria to predict trauma center need (TCN) were compared. RESULTS: In total, 4,480,185 patients were analyzed (28% geriatric). Geriatric patients more frequently presented with non-motor-only deficits than adults (16.4% versus 12.4%, P < 0.001), and these patients demonstrated higher severe TBI (40.3% versus 36.7%, P < 0.001) and craniotomy (5.8% versus 5.1%, P < 0.001) rates. GCSt was more sensitive and accurate in predicting TCN for geriatric patients and had lower rates of undertriage as compared to GCSm. CONCLUSIONS: Geriatric patients more frequently present with non-motor-only deficits after injury, and this is associated with severe head injury. Substitution of GCSm for GCSt would exacerbate undertriage in geriatric patients and, thus, the total GCS should be maintained for field triage in geriatric patients.

Impact of Volume Change Over Time on Trauma Mortality in the United States.

OBJECTIVE: To evaluate the association of trauma center volume change over time with mortality. BACKGROUND: Regionalization of trauma systems assumes a volume-outcome relationship for severe injury. Whereas this has been shown for cross-sectional volume, it is unclear whether volume changes over time translate into predictable outcome changes. METHODS: Retrospective cohort study of severely injured (injury severity score >15) patients from the National Trauma Databank 2000 to 2012. A center-level standardized mortality ratio (SMR) was constructed (ratio of observed to expected deaths). Expected mortality was obtained from multilevel logistic regression model, adjusting for demographics, mechanism, vital signs, and injury severity. Center-level percent volume change was assessed across early (2000-2006) and late (2007-2012) periods. Longitudinal panel modeling evaluated association between annual SMR change and volume change over preceding years. RESULTS: There were 839,809 patients included from 287 centers. Each 1% increase in volume was associated with 73% increased odds of improving SMR over time [odds ratio (OR) 1.73; 95% confidence interval (CI) 1.03-2.91; P = 0.03]. Each 1% decrease in volume was associated with 2-fold increase in odds of worsening SMR over time (OR 2.14; 95% CI 1.07-4.26, P = 0.03). Significant improvement in the SMR emerged after 3 or more preceding years of increasing volume (SMR change -0.008; 95% CI -0.015, -0.002; P = 0.01). This benefit occurred only in centers that were level I or II verified. CONCLUSIONS: Increasing volume was associated with improving outcomes, whereas decreasing volume was associated with worsening outcomes. High-level trauma center infrastructure seems to facilitate the volume-outcome relationship. The trauma center designation process should consider volume changes in the overall system.

Should All Massively Transfused Patients Be Treated Equally? An Analysis of Massive Transfusion Ratios in the Nontrauma Setting.

OBJECTIVES: Although balanced resuscitation has become integrated into massive transfusion practice, there is a paucity of evidence supporting the delivery of high ratios of plasma and platelet to RBCs in the nontrauma setting. This study investigated the administration of blood component ratios in the massively transfused nontrauma demographic. DESIGN: Retrospective analysis of a prospective, observational cohort of massively bleeding patients. SETTING: Surgical and critically ill patients at a tertiary medical center between 2011 and 2015. PATIENTS: Massively transfused nontrauma patients. INTERVENTIONS: Patients receiving plasma, platelet, and RBC transfusions were categorized into high and low ratio groups and analyzed for differences in characteristics and clinical outcomes. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 30-day mortality. Secondary outcomes included 48-hour mortality, hospital length of stay, ICU length of stay, and ventilator-free days. Among 601 massively transfused nontrauma patients, cardiothoracic surgery and gastrointestinal or hepato-pancreatico-biliary bleeds were the most common indications for massive transfusion. Higher fresh frozen plasma ratios (> 1:2) were not associated with increased 30-day mortality. A high platelets-to-packed RBCs ratio (> 1:2) was associated with decreased 48-hour mortality (10.5% vs 19.3%; p = 0.032), but not 30-day mortality. Fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs ratios were not associated with 30-day mortality hazard ratios after controlling for baseline characteristics and disease severity. CONCLUSIONS: The benefits of higher ratios of fresh frozen plasma-to-packed RBCs and platelets-to-packed RBCs described in trials of trauma patients were not observed in this analysis of a nontrauma, massively transfused population. These data suggest that greater than 1:2 ratio transfusion in the setting of massive hemorrhage may not be appropriate for all patients, and that further research to guide appropriate resuscitation strategies in nontrauma patients is warranted.

Development and Validation of the Air Medical Prehospital Triage Score for Helicopter Transport of Trauma Patients.

OBJECTIVE: The aim of this study was to develop and internally validate a triage score that can identify trauma patients at the scene who would potentially benefit from helicopter emergency medical services (HEMS). SUMMARY BACKGROUND DATA: Although survival benefits have been shown at the population level, identification of patients most likely to benefit from HEMS transport is imperative to justify the risks and cost of this intervention. METHODS: Retrospective cohort study of subjects undergoing scene HEMS or ground emergency medical services (GEMS) in the National Trauma Databank (2007-2012). Data were split into training and validation sets. Subjects were grouped by triage criteria in the training set and regression used to determine which criteria had a survival benefit associated with HEMS. Points were assigned to these criteria to develop the Air Medical Prehospital Triage (AMPT) score. The score was applied in the validation set to determine whether subjects triaged to HEMS had a survival benefit when actually transported by helicopter. RESULTS: There were 2,086,137 subjects included. Criteria identified for inclusion in the AMPT score included GCS <14, respiratory rate <10 or >29, flail chest, hemo/pneumothorax, paralysis, and multisystem trauma. The optimal cutoff for triage to HEMS was ≥2 points. In subjects triaged to HEMS, actual transport by HEMS was associated with an increased odds of survival (AOR 1.28; 95% confidence interval [CI] 1.21-1.36, P < 0.01). In subjects triaged to GEMS, actual transport mode was not associated with survival (AOR 1.04; 95% CI 0.97-1.11, P = 0.20). CONCLUSIONS: The AMPT score identifies patients with improved survival following HEMS transport and should be considered in air medical triage protocols.

Geographic Variation in Outcome Benefits of Helicopter Transport for Trauma in the United States: A Retrospective Cohort Study.

OBJECTIVE: Evaluate the effect of US geographic region on outcomes of helicopter transport (HT) for trauma. BACKGROUND: HT is an integral component of trauma systems. Evidence suggests that HT is associated with improved outcomes; however, no studies examine the impact of geographic variation on outcomes for HT. METHODS: Retrospective cohort study of patients undergoing scene HT or ground transport in the National Trauma Databank (2009-2012). Subjects were divided by US census region. HT and ground transport subjects were propensity-score matched based on prehospital physiology and injury severity. Conditional logistic regression was used to evaluate the effect of HT on survival and discharge to home in each region. Region-level characteristics were assessed as potential explanatory factors. RESULTS: A total of 193,629 pairs were matched. HT was associated with increased odds of survival and discharge to home; however, the magnitude of these effects varied significantly across regions (P < 0.01). The South had the greatest survival benefit (odds ratio: 1.44; 95% confidence interval: 1.39-1.49, P < 0.01) and the Northeast had the greatest discharge to home benefit (odds ratio: 1.29; 95% confidence interval: 1.18-1.41, P < 0.01). A subset of region-level characteristics influenced the effect of HT on each outcome, including helicopter utilization, injury severity, trauma center and helicopter distribution, trauma center access, traffic congestion, and urbanicity (P < 0.05). CONCLUSIONS: Geographic region impacts the benefits of HT in trauma. Variations in resource allocation partially account for outcome differences. Policy makers should consider regional factors to better assess and allocate resources within trauma systems to optimize the role of HT.

Temporal Patterns of Circulating Inflammation Biomarker Networks Differentiate Susceptibility to Nosocomial Infection Following Blunt Trauma in Humans.

BACKGROUND: Severe traumatic injury can lead to immune dysfunction that renders trauma patients susceptible to nosocomial infections (NI) and prolonged intensive care unit (ICU) stays. We hypothesized that early circulating biomarker patterns following trauma would correlate with sustained immune dysregulation associated with NI and remote organ failure. METHODS: In a cohort of 472 blunt trauma survivors studied over an 8-year period, 127 patients (27%) were diagnosed with NI versus 345 trauma patients without NI. To perform a pairwise, case-control study with 1:1 matching, 44 of the NI patients were compared with 44 no-NI trauma patients selected by matching patient demographics and injury characteristics. Plasma obtained upon admission and over time were assayed for 26 inflammatory mediators and analyzed for the presence of dynamic networks. RESULTS: Significant differences in ICU length of stay (LOS), hospital LOS, and days on mechanical ventilation were observed in the NI patients versus no-NI patients. Although NI was not detected until day 7, multiple mediators were significantly elevated within the first 24 hours in patients who developed NI. Circulating inflammation biomarkers exhibited 4 distinct dynamic patterns, of which 2 clearly distinguish patients destined to develop NI from those who did not. Mediator network connectivity analysis revealed a higher, coordinated degree of activation of both innate and lymphoid pathways in the NI patients over the initial 24 hours. CONCLUSIONS: These studies implicate unique dynamic immune responses, reflected in circulating biomarkers that differentiate patients prone to persistent critical illness and infections following injury, independent of mechanism of injury, injury severity, age, or sex.

Elevated Admission Base Deficit Is Associated with a Complex Dynamic Network of Systemic Inflammation Which Drives Clinical Trajectories in Blunt Trauma Patients.

We hypothesized that elevated base deficit (BD) ≥ 4 mEq/L upon admission could be associated with an altered inflammatory response, which in turn may impact differential clinical trajectories. Using clinical and biobank data from 472 blunt trauma survivors, 154 patients were identified after excluding patients who received prehospital IV fluids or had alcohol intoxication. From this subcohort, 84 patients had a BD ≥ 4 mEq/L and 70 patients with BD < 4 mEq/L. Three samples within the first 24 h were obtained from all patients and then daily up to day 7 after injury. Twenty-two cytokines and chemokines were assayed using Luminex™ and were analyzed using two-way ANOVA and dynamic network analysis (DyNA). Multiple mediators of the innate and lymphoid immune responses in the BD ≥ 4 group were elevated differentially upon admission and up to 16 h after injury. DyNA revealed a higher, sustained degree of interconnectivity of the inflammatory response in the BD ≥ 4 patients during the initial 16 h after injury. These results suggest that elevated admission BD is associated with differential immune/inflammatory pathways, which subsequently could predispose patients to follow a complicated clinical course.

Pretrauma center red blood cell transfusion is associated with reduced mortality and coagulopathy in severely injured patients with blunt trauma.

OBJECTIVE: To evaluate the association of pretrauma center (PTC) red blood cell (RBC) transfusion with outcomes in severely injured patients. BACKGROUND: Hemorrhage remains a major driver of mortality. Little evidence exists supporting PTC interventions to mitigate this. METHODS: Blunt injured patients in shock arriving at a trauma center within 2 hours of injury were included from the Glue Grant database. Subjects were dichotomized by PTC RBC transfusion. Outcomes included 24-hour mortality, 30-day mortality, and trauma-induced coagulopathy [(TIC), admission international normalized ratio >1.5]. Cox regression and logistic regression determined the association of PTC RBC transfusion with outcomes. To address baseline differences, propensity score matching was used. RESULTS: Of 1415 subjects, 50 received PTC RBC transfusion. Demographics and injury severity score were similar. The PTC RBC group received 1.3 units of RBCs (median), and 52% were scene transports. PTC RBC transfusion was associated with a 95% reduction in odds of 24-hour mortality [odds ratio (OR) = 0.05; 95% confidence interval (CI), 0.01-0.48; P < 0.01], 64% reduction in the risk of 30-day mortality [hazard ratio = 0.36; 95% CI, 0.15-0.83; P = 0.02], and 88% reduction in odds of TIC (OR = 0.12; 95% CI, 0.02-0.79; P = 0.03). The matched cohort included 113 subjects (31% PTC RBC group). Baseline characteristics were similar. PTC RBC transfusion was associated with a 98% reduction in odds of 24-hour mortality (OR = 0.02; 95% CI, 0.01-0.69; P = 0.04), 88% reduction in the risk of 30-day mortality (hazard ratio = 0.12; 95% CI, 0.03-0.61; P = 0.01), and 99% reduction in odds of TIC (OR = 0.01; 95% CI, 0.01-0.95; P = 0.05). CONCLUSIONS: PTC RBC administration was associated with a lower risk of 24-hour mortality, 30-day mortality, and TIC in severely injured patients with blunt trauma, warranting further prospective study.

Design of the Study of Tranexamic Acid during Air Medical Prehospital Transport (STAAMP) Trial: Addressing the Knowledge Gaps.

Abstract Hemorrhage and coagulopathy remain major drivers of early preventable mortality in military and civilian trauma. The development of trauma-induced coagulopathy and hyperfibrinolysis is associated with poor outcomes. Interest in the use of tranexamic acid (TXA) in hemorrhaging patients as an antifibrinolytic agent has grown recently. Additionally, several reports describe immunomodulatory effects of TXA that may confer benefit independent of its antifibrinolytic actions. A large trial demonstrated a mortality benefit for early TXA administration in patients at risk for hemorrhage; however, questions remain about the applicability in developed trauma systems and the mechanism by which TXA reduces mortality. We describe here the rationale, design, and challenges of the Study of Tranexamic Acid during Air Medical Prehospital transport (STAAMP) trial. The primary objective is to determine the effect of prehospital TXA infusion during air medical transport on 30-day mortality in patients at risk of traumatic hemorrhage. This study is a multicenter, placebo-controlled, double-blind, randomized clinical trial. The trial will enroll trauma patients with hypotension and tachycardia from 4 level I trauma center air medical transport programs. It includes a 2-phase intervention, with a prehospital and in-hospital phase to investigate multiple dosing regimens. The trial will also explore the effects of TXA on the coagulation and inflammatory response following injury. The trial will be conducted under exception for informed consent for emergency research and thus required an investigational new drug approval from the U.S. Food and Drug Administration as well as a community consultation process. It was designed to address several existing knowledge gaps and research priorities regarding TXA use in trauma.

Taking the Blood Bank to the Field: The Design and Rationale of the Prehospital Air Medical Plasma (PAMPer) Trial.

Hemorrhage and trauma induced coagulopathy remain major drivers of early preventable mortality in military and civilian trauma. Interest in the use of prehospital plasma in hemorrhaging patients as a primary resuscitation agent has grown recently. Trauma center-based damage control resuscitation using early and aggressive plasma transfusion has consistently demonstrated improved outcomes in hemorrhaging patients. Additionally, plasma has been shown to have several favorable immunomodulatory effects. Preliminary evidence with prehospital plasma transfusion has demonstrated feasibility and improved short-term outcomes. Applying state-of-the-art resuscitation strategies to the civilian prehospital arena is compelling. We describe here the rationale, design, and challenges of the Prehospital Air Medical Plasma (PAMPer) trial. The primary objective is to determine the effect of prehospital plasma transfusion during air medical transport on 30-day mortality in patients at risk for traumatic hemorrhage. This study is a multicenter cluster randomized clinical trial. The trial will enroll trauma patients with profound hypotension (SBP ≤ 70 mmHg) or hypotension (SBP 71-90 mmHg) and tachycardia (HR ≥ 108 bpm) from six level I trauma center air medical transport programs. The trial will also explore the effects of prehospital plasma transfusion on the coagulation and inflammatory response following injury. The trial will be conducted under exception for informed consent for emergency research with an investigational new drug approval from the U.S. Food and Drug Administration utilizing a multipronged community consultation process. It is one of three ongoing Department of Defense-funded trials aimed at expanding our understanding of the optimal therapeutic approaches to coagulopathy in the hemorrhaging trauma patient.

X chromosome-linked IRAK-1 polymorphism is a strong predictor of multiple organ failure and mortality postinjury.

OBJECTIVE(S): Clinical research characterizing the mechanisms responsible for sex-based outcome differences postinjury remain conflicting. We sought to characterize an X chromosome-linked IRAK-1 (IL-1 receptor-associated kinase) polymorphism as an alternative mechanism responsible for sex differences postinjury. IRAK-1 is key intermediate in the toll-like receptor (TLR) pathway thought to drive inflammation postinjury. METHODS: A prospective cohort study was performed over a 24-month period. Bluntly injured patients requiring intensive care unit admission were enrolled, whereas patients with isolated brain and spinal cord injuries were excluded. Outcomes of interest included multiple organ failure (MOF, Marshall MOD score > 5) and mortality. Logistic regression was utilized to determine the independent risk of poor outcome associated with the IRAK-1 variant after controlling for important differences. RESULTS: In an enrolled cohort of 321 patients, the IRAK-1 variant was common (12.5%). Patients with and without the variant were similar in age, injury severity, and 24hr blood transfusion. After controlling for important confounders, the IRAK1 variant was independently associated with more than eightfold (OR = 8.4, P = 0.005, 95% CI: 1.9-37.1) and 11-fold (OR = 11.8, P = 0.037, 95% CI: 1.1-121) greater risk of MOF and mortality, respectively. These differences were most prominent in men, whereas women heterozygous for the variant demonstrated worse outcome in a dose-dependent fashion. CONCLUSIONS: The IRAK1 polymorphism is a strong independent predictor of MOF and mortality postinjury and represents a common variant with prognostic potential. These data demonstrate the importance of TLR signaling postinjury and supports that a genetic mechanism may drive sex outcome differences postinjury.

Prehospital use of nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with a reduced incidence of trauma-induced coagulopathy.

OBJECTIVE: To determine whether prehospital nonsteroidal anti-inflammatory drug (NSAID) use may lead to a reduced incidence of trauma-induced coagulopathy (TIC) in severely injured patients. BACKGROUND: TIC is present in up to a quarter of severely injured trauma patients and is linked to worse outcomes after injury. Evidence linking TIC to inflammation has emerged; however, the mechanism behind this association is still under investigation. NSAIDs are commonly used anti-inflammatory drugs, but their effects on TIC and outcomes after injury are largely unexplored. METHODS: We performed a secondary analysis of the Inflammation and the Host Response to Injury Large Scale Collaborative Program (Glue Grant) data set. Prehospital medications and comorbidities were analyzed by logistic regression analysis for association with TIC as defined by laboratory (international normalized ratio >1.5) or clinical (transfusion >2 units of fresh frozen plasma or >1 pack of platelets in 6 hours) parameters. RESULTS: Prehospital NSIAD use was independently associated with a 72% lower risk of TIC and was the only medication among 15 analyzed to retain significance in the model. Stepwise logistic regression also demonstrated that preadmission use of NSAIDs was independently associated with a 66% lower risk of clinically significant coagulopathy. These findings were independent of comorbid conditions linked to NSAID use. CONCLUSIONS: NSAID use before admission for severe injury is associated with a reduced incidence of TIC. These findings provide further evidence to a potential leak between TIC and inflammation.

The Difficult Cholecystectomy: What You Need to Know.

ABSTRACT: This review discusses the grading of cholecystitis, the optimal timing of cholecystectomy, adopting a culture of safe cholecystectomy, understanding the common error traps that can lead to intraoperative complications and how to avoid them. The Tokyo Guidelines, AAST, Nassar and Parkland scoring systems are discussed. The patient factors, physiologic status and operative findings that predict a difficult cholecystectomy or conversion from laparoscopic to open cholecystectomy are reviewed. With laparoscopic expertise and patient conditions that are not prohibitive, early laparoscopic cholecystectomy is recommended. This is ideally within 72 hours of admission but supported up to the seventh hospital day. The majority of bile duct injuries (BDI) are due to misidentification of normal anatomy. Strasberg's four error traps and the zones of danger to avoid during a cholecystectomy are described. The review emphasizes the importance of a true critical view of safety (CVS) for identification of the anatomy. In up to 15% of operations for acute cholecystitis, a CVS cannot be achieved safely. Recognizing these conditions and changing your operative strategy are mandatory to avoid harm. The principles to follow for a safe cholecystectomy are discussed in detail. The cardinal message of this review is "under challenging conditions, BDI can be minimized via either a subtotal cholecystectomy or top-down cholecystectomy if dissection in the hepatocystic triangle is avoided." (28) The most severe biliary/vascular injuries usually occur after conversion from laparoscopic cholecystectomy. Indications and techniques for bailout procedures including the fenestrating and reconstituting subtotal cholecystectomy are presented. Seven to ten percent of cholecystectomies for acute cholecystitis currently result in subtotal cholecystectomy.

Evaluating potential disparities in geospatial access to American College of Surgeons/American Association for the Surgery of Trauma-verified emergency general surgery centers.

BACKGROUND: The American Association for the Surgery of Trauma and the American College of Surgeons have recently introduced emergency general surgery (EGS) center verification, which could enhance patient outcomes. Distance and resource availability may affect access to these centers, which has been linked to higher mortality. Although many patients can receive adequate care at community centers, those with critical conditions may require specialized treatment at EGS-verified centers. We aimed to evaluate geospatial access to potential EGS-verified centers and identify disparities across different scenarios of EGS verification program uptake in the United States. METHODS: We used hospital capabilities and verified pilot centers to estimate potential patterns of which centers would become EGS verified under four scenarios (EGS centers, high-volume EGS centers, high-volume EGS plus level 1 trauma centers, and quaternary referral centers). We calculated the spatial accessibility index using an enhanced two-step floating catchment technique to determine geospatial access for each scenario. We also evaluated social determinants of health across geospatial access using the Area Deprivation Index (ADI). RESULTS: A total of 1,932 hospitals were categorized as EGS centers, 307 as high-volume EGS centers, 401 as high-volume EGS plus level 1trauma centers, and 146 as quaternary centers. Spatial accessibility index decreased as the stringency of EGS verification increased in each scenario (226.6 [111.7-330.7], 51.8 [0-126.1], 71.52 [3.34-164.56], 6.2 [0-62.2]; p < 0.001). Within each scenario, spatial accessibility index also declined as the ADI quartile increased ( p < 0.001). The high-volume EGS plus level 1trauma center scenario had the most significant disparity in access between the first and fourth ADI quartiles (-54.68). CONCLUSION: Access to EGS-verified centers may vary considerably based on the program's implementation. Disadvantaged communities may be disproportionately affected by limited access. Further work to study regional needs can allow a strategic implementation of the EGS verification program to optimize outcomes while minimizing disparities. LEVEL OF EVIDENCE: Prognostic and Epidemiological; Level IV.

Association between timing of operative interventions and mortality in emergency general surgery.

Background: Emergency general surgery (EGS) often demands timely interventions, yet data for triage and timing are limited. This study explores the relationship between hospital arrival-to-operation time and mortality in EGS patients. Study design: We performed a retrospective cohort study using an EGS registry at four hospitals, enrolling adults who underwent operative intervention for a primary American Association for the Surgery of Trauma-defined EGS diagnosis between 2021 and 2023. We excluded patients undergoing surgery more than 72 hours after admission as non-urgent and defined our exposure of interest as the time from the initial vital sign capture to the skin incision timestamp. We assessed the association between operative timing quintiles and in-hospital mortality using a mixed-effect hierarchical multivariable model, adjusting for patient demographics, comorbidities, organ dysfunction, and clustering at the hospital level. Results: A total of 1199 patients were included. The median time to operating room (OR) was 8.2 hours (IQR 4.9-20.5 hours). Prolonged time to OR increased the relative likelihood of in-hospital mortality. Patients undergoing an operation between 6.7 and 10.7 hours after first vitals had the highest odds of in-hospital mortality compared with operative times <4.2 hours (reference quintile) (adjusted OR (aOR) 68.994; 95% CI 4.608 to 1032.980, p=0.002). A similar trend was observed among patients with operative times between 24.4 and 70.9 hours (aOR 69.682; 95% CI 2.968 to 1636.038, p=0.008). Conclusion: Our findings suggest that prompt operative intervention is associated with lower in-hospital mortality rates among EGS patients. Further work to identify the most time-sensitive populations is warranted. These results may begin to inform benchmarking for triaging interventions in the EGS population to help reduce mortality rates. Level of evidence: IV.