Diagnostic Adjunct Techniques in the Assessment of Hypovolemia: A Prospective Pilot Project.

INTRODUCTION: Measuring the hypovolemic resuscitation end point remains a critical care challenge. Our project compared clinical hypovolemia (CH) with three diagnostic adjuncts: 1) noninvasive cardiac output monitoring (NICOM), 2) ultrasound (US) static IVC collapsibility (US-IVC), and 3) US dynamic carotid upstroke velocity (US-C). We hypothesized US measures would correlate more closely to CH than NICOM. METHODS: Adult trauma/surgical intensive care unit patients were prospectively screened for suspected hypovolemia after acute resuscitation, excluding patients with burns, known heart failure, or severe liver/kidney disease. Adjunct measurements were assessed up to twice a day until clinical improvement. Hypovolemia was defined as: 1) NICOM: ≥10% stroke volume variation with passive leg raise, 2) US-IVC: <2.1 cm and >50% collapsibility (nonventilated) or >18% collapsibility (ventilated), 3) US-C: peak systolic velocity increase 15 cm/s with passive leg raise. Previously unknown cardiac dysfunction seen on US was noted. Observation-level data were analyzed with a Cohen's kappa (κ). RESULTS: 44 patients (62% male, median age 60) yielded 65 measures. Positive agreement with CH was 47% for NICOM, 37% for US-IVC and 10% for US-C. None of the three adjuncts correlated with CH (κ -0.045 to 0.029). After adjusting for previously unknown cardiac dysfunction present in 10 patients, no adjuncts correlated with CH (κ -0.036 to 0.031). No technique correlated with any other (κ -0.118 to 0.083). CONCLUSIONS: None of the adjunct measurements correlated with CH or each other, highlighting that fluid status assessment remains challenging in critical care. US should assess for right ventricular dysfunction prior to resuscitation.

Functional Status is Key to Long-term Survival in Emergency General Surgery Conditions.

INTRODUCTION: Emergency General Surgery (EGS) conditions in older patients constitutes a substantial public health burden due to high morbidity and mortality. We sought to utilize a supervised machine learning method to determine combinations of factors with the greatest influence on long-term survival in older EGS patients. METHODS: We identified community dwelling participants admitted for EGS conditions from the Medicare Current Beneficiary Survey linked with claims (1992-2013). We categorized three binary domains of multimorbidity: chronic conditions, functional limitations, and geriatric syndromes (such as vision or hearing impairment, falls, incontinence). We also collected EGS disease type, age, and sex. We created a classification and regression tree (CART) model to identify groups of variables associated with our outcome of interest, three-year survival. We then performed Cox proportional hazards analysis to determine hazard ratios for each group with the lowest risk group as reference. RESULTS: We identified 1960 patients (median age 79 [interquartile range [IQR]: 73, 85], 59.5% female). The CART model identified the presence of functional limitations as the primary splitting variable. The lowest risk group were patient aged ≤81 y with biliopancreatic disease and without functional limitations. The highest risk group was men aged ≥75 y with functional limitations (hazard ratio [HR] 11.09 (95% confidence interval [CI] 5.91-20.83)). Notably absent from the CART model were chronic conditions and geriatric syndromes. CONCLUSIONS: More than the presence of chronic conditions or geriatric syndromes, functional limitations are an important predictor of long-term survival and must be included in presurgical assessment.

Development of Imaging Criteria for Geriatric Blunt Trauma Patients.

INTRODUCTION: Current decision tools to guide trauma computed tomography (CT) imaging were not validated for use in older patients. We hypothesized that specific clinical variables would be predictive of injury and could be used to guide imaging in this population to minimize risk of missed injury. METHODS: Blunt trauma patients aged 65 y and more admitted to a Level 1 trauma center intensive care unit from January 2018 to November 2020 were reviewed for histories, physical examination findings, and demographic information known at the time of presentation. Injuries were defined using the patient's final abbreviated injury score codes, obtained from the trauma registry. Abbreviated injury score codes were categorized by corresponding CT body region: Head, Face, Chest, C-Spine, Abdomen/Pelvis, or T/L-Spine. Variable groupings strongly predictive of injury were tested to identify models with high sensitivity and a negative predictive value. RESULTS: We included 608 patients. Median age was 77 y (interquartile range, 70-84.5) and 55% were male. Ground-level fall was the most common injury mechanism. The most commonly injured CT body regions were Head (52%) and Chest (42%). Variable groupings predictive of injury were identified in all body regions. We identified models with 97.8% sensitivity for Head and 98.8% for Face injuries. Sensitivities more than 90% were reached for all except C-Spine and Abdomen/Pelvis. CONCLUSIONS: Decision aids to guide imaging for older trauma patients are needed to improve consistency and quality of care. We have identified groupings of clinical variables that are predictive of injury to guide CT imaging after geriatric blunt trauma. Further study is needed to refine and validate these models.

High Dimensional Multiomics Reveals Unique Characteristics of Early Plasma Administration in Polytrauma Patients With TBI.

OBJECTIVES: The authors sought to identify causal factors that explain the selective benefit of prehospital administration of thawed plasma (TP) in traumatic brain injury (TBI) patients using mediation analysis of a multiomic database. BACKGROUND: The Prehospital Air Medical Plasma (PAMPer) Trial showed that patients with TBI and a pronounced systemic response to injury [defined as endotype 2 (E2)], have a survival benefit from prehospital administration of TP. An interrogation of high dimensional proteomics, lipidomics and metabolomics previously demonstrated unique patterns in circulating biomarkers in patients receiving prehospital TP, suggesting that a deeper analysis could reveal causal features specific to TBI patients. METHODS: A novel proteomic database (SomaLogic Inc., aptamer-based assay, 7K platform) was generated using admission blood samples from a subset of patients (n=149) from the PAMPer Trial. This proteomic dataset was combined with previously reported metabolomic and lipidomic datasets from these same patients. A 2-step analysis was performed to identify factors that promote survival in E2-TBI patients who had received early TP. First, features were selected using both linear and multivariate-latent-factor regression analyses. Then, the selected features were entered into the causal mediation analysis. RESULTS: Causal mediation analysis of observable features identified 16 proteins and 41 lipids with a high proportion of mediated effect (>50%) to explain the survival benefit of early TP in E2-TBI patients. The multivariate latent-factor regression analyses also uncovered 5 latent clusters of features with a proportion effect >30%, many in common with the observable features. Among the observable and latent features were protease inhibitors known to inhibit activated protein C and block fibrinolysis (SERPINA5 and CPB2), a clotting factor (factor XI), as well as proteins involved in lipid transport and metabolism (APOE3 and sPLA(2)-XIIA). CONCLUSIONS: These findings suggest that severely injured patients with TBI process exogenous plasma differently than those without TBI. The beneficial effects of early TP in E2-TBI patients may be the result of improved blood clotting and the effect of brain protective factors independent of coagulation.

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 .).

"What Are My Injuries?" Health Literacy and Patient Comprehension of Trauma Care and Injuries.

BACKGROUND: Trauma patients often have complex injuries treated by multidisciplinary providers with wide-ranging expertise. We hypothesized that trauma patients would frequently incorrectly identify both their injuries and care teams. We also hypothesized that low health literacy level would be correlated with low levels of comprehension about injuries or care teams. MATERIALS AND METHODS: We performed a prospective study of adult trauma inpatients >18 years. Participants were surveyed to report on 1) injured body regions 2) their care teams, and 3) health literacy via a validated survey. Self-reported injuries and care teams were compared to the patient's medical record. We also studied whether health literacy was associated with patient knowledge of injuries and care teams. RESULTS: Fifty participants were surveyed; thirty-two percent could not identify ≥50% of their injuries. Patients reliably identified injuries to the head, but injuries to other body areas were often misidentified. Forty-two percent of patients were not able to identify ≥50% of their medical teams, and 28% could not identify ≥75% of their medical teams. Patients often did not recognize teams such as nutrition, physical/occupationalt, or social work as part of their care. Thirteen participants reported adequate health literacy. Health literacy was not related to participant knowledge of injuries or care teams (both P = 0.9). CONCLUSION: Many trauma inpatients were unable to correctly identify their injuries and care teams despite a range of self-reported health literacy scores.

Goals of Care Discussions for the Imminently Dying Trauma Patient.

BACKGROUND: A structured family meeting (FM) is recommended within 72 h of admission for trauma patients with high risk of mortality or disability. Multidisciplinary FMs (MDFMs) may further facilitate decision-making. We hypothesized that FM within three hospital days (HDs) or MDFM would be associated with increased use of comfort measures. MATERIALS AND METHODS: We reviewed all adult trauma deaths at an academic level 1 trauma center from December 2014 to December 2017. Death in the first 24 h or on nonsurgical services were excluded. Demographics, injury characteristics, FM characteristics, and outcomes such as length of stay (LOS) were recorded. Early FM was defined as occurring within three HDs; MDFM required attendance by two or more specialty teams. RESULTS: A total of 177 patients were included. Median LOS was 6 d (interquartile range 4-12). FMs were documented in 166 patients (94%), with 57% occurring early. MDFM occurred in 49 (28%), but usually occurred later (median HD 5 and interquartile range 2-8). Early FM was associated with reduced LOS (5 versus 11 d, P < 0.001), ventilator days (4 versus 9 d, P < 0.001), and deaths during a code (1.2% versus 13.2%, P < 0.001). MDFM was associated with higher use of comfort measures (88% versus 68%, P < 0.05). Of patients who transitioned to comfort care status (n = 130, 73.4%), code status change occurred earlier if an early FM occurred (5 versus 13 d, P < 0.001). CONCLUSIONS: MDFM is associated with increased comfort care measures, whereas early FM is associated with reduced LOS, ventilator days, death during a code, and earlier comfort care transition.

Factors Influencing Nonadherence to Recommended Postdischarge Follow-Up After Trauma.

INTRODUCTION: Historically, trauma patients have low adherence to recommended outpatient follow-up plans, which is crucial for improved long-term clinical outcomes. We sought to identify characteristics associated with nonadherence to recommended outpatient follow-up visits. METHODS: This is a single-center retrospective examination of inpatient trauma survivors admitted to a level 1 trauma center (March 2017-March 2018). Patients with known alternative follow-up were excluded. All outpatient visits within 1 y from the index admission were identified. The primary outcome was nonadherence, which was noted if a patient failed to follow-up for any specialty recommended in the discharge instructions. Factors for nonadherence studied included age, injury severity score, mechanism, length of stay, number of referrals made, and involvement with a Trauma Recovery Services program. Bivariate and logistic regression analyses were performed. RESULTS: A total of498 patients were identified (69% men, median age 43 y [range, 26-58 y], median injury severity score 14 [range, 9-19]). Among them, 240 (47%) were nonadherent. The most common specialties recommended were orthopedic surgery (56% referred, 19% nonadherent), trauma (54% referred, 35% nonadherent), and neurosurgery (127 referred, 35% nonadherent). Lowest levels of follow-up were seen for nonsurgical referrals. In adjusted analysis, a higher number of referrals made (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.95-3.05) and older age (OR, 1.01; 95% CI, 1.00-1.02) were associated with nonadherence. Trauma Recovery Service participants and penetrating trauma patients were more likely to be adherent (OR, 0.60; 95% CI, 0.37-0.97). CONCLUSIONS: The largest contributor to nonadherence was the number of referrals made; patients who were referred to multiple specialists were more likely to be nonadherent. Peer support services may lower barriers to follow-up.

Trial of short-course antimicrobial therapy for intraabdominal infection.

BACKGROUND: The successful treatment of intraabdominal infection requires a combination of anatomical source control and antibiotics. The appropriate duration of antimicrobial therapy remains unclear. METHODS: We randomly assigned 518 patients with complicated intraabdominal infection and adequate source control to receive antibiotics until 2 days after the resolution of fever, leukocytosis, and ileus, with a maximum of 10 days of therapy (control group), or to receive a fixed course of antibiotics (experimental group) for 4±1 calendar days. The primary outcome was a composite of surgical-site infection, recurrent intraabdominal infection, or death within 30 days after the index source-control procedure, according to treatment group. Secondary outcomes included the duration of therapy and rates of subsequent infections. RESULTS: Surgical-site infection, recurrent intraabdominal infection, or death occurred in 56 of 257 patients in the experimental group (21.8%), as compared with 58 of 260 patients in the control group (22.3%) (absolute difference, -0.5 percentage point; 95% confidence interval [CI], -7.0 to 8.0; P=0.92). The median duration of antibiotic therapy was 4.0 days (interquartile range, 4.0 to 5.0) in the experimental group, as compared with 8.0 days (interquartile range, 5.0 to 10.0) in the control group (absolute difference, -4.0 days; 95% CI, -4.7 to -3.3; P<0.001). No significant between-group differences were found in the individual rates of the components of the primary outcome or in other secondary outcomes. CONCLUSIONS: In patients with intraabdominal infections who had undergone an adequate source-control procedure, the outcomes after fixed-duration antibiotic therapy (approximately 4 days) were similar to those after a longer course of antibiotics (approximately 8 days) that extended until after the resolution of physiological abnormalities. (Funded by the National Institutes of Health; STOP-IT ClinicalTrials.gov number, NCT00657566.).

Novel Method Suggests Global Superiority of Short-Duration Antibiotics for Intra-abdominal Infections.

Desirability of outcome ranking and response adjusted for duration of antibiotic risk (DOOR/RADAR) are novel and innovative methods of evaluating data in antibiotic trials. We analyzed data from a noninferiority trial of short-course antimicrobial therapy for intra-abdominal infection (STOP-IT), and results suggest global superiority of short-duration therapy for intra-abdominal infections.

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.

Trends in maxillofacial trauma: a comparison of two cohorts of patients at a single institution 20 years apart.

PURPOSE: The purpose of this study was to compare and characterize 2 cohorts of patients with maxillofacial fractures within the same institution over 2 6-year time frames 20 years apart. MATERIALS AND METHODS: A retrospective review of patients with maxillofacial fractures at the authors' institution from 2004 to 2010 was performed, and a comparison was made with the authors' experience from 1984 to 1990. RESULTS: The 1990 study showed 458 maxillofacial fractures (152 midface and 306 mandibular fractures). In the 2010 study, there were 1,731 maxillofacial fractures (1,313 midface and 418 mandibular fractures). There were significant differences in the mechanism of injury between the 1990 and 2010 studies: assaults decreased from 48.8% to 29.7%, motor vehicle collisions decreased from 39.1% to 29.6%, and falls increased from 3.6% to 22.1%. Comparison by age categories showed major changes in the following groups: maxillofacial fractures in patients 21 to 40 years old decreased from 61.7% to 35.3%, those in patients 41 to 65 years old increased from 13.1% to 35.4%, and those in patients at least 66 years old (elderly) increased from 0.2% to 14.5%. All these changes were statistically significant (P < .0001). CONCLUSION: Maxillofacial trauma has changed significantly over the past 2 decades in the authors' institution. A decrease in assault-related injuries in the younger populations and an increase in the incidence of falls in the elderly were the main differences. There was a significant increase in elderly patients with maxillofacial trauma. This change emphasizes the need for adequate prevention programs and appropriate maxillofacial surgery teams to manage these injuries in the older patient.

Fracture related infection and sepsis in orthopedic trauma: A review.

Trauma is a leading cause of death in the United States for people under 45. Amongst trauma-related injuries, orthopedic injuries represent a significant component of trauma-related morbidity. In addition to the potential morbidity and mortality secondary to the specific traumatic injury or injuries sustained, sepsis is a significant cause of morbidity and mortality in trauma patients as well, and infection related to orthopedic trauma can be especially devastating. Therefore, infection prevention and early recognition of infections is crucial to lowering morbidity and mortality in trauma. Risk factors for fracture-related infection include obesity, tobacco use, open fracture, and need for flap coverage, as well as fracture of the tibia and the degree of contamination. Timely administration of prophylactic antibiotics for patients presenting with open fractures has been shown to decrease the risk of fracture-related infection, and in patients that do experience sepsis from an orthopedic injury, prompt source control is critical, which may include the removal of implanted hardware in infections that occur more than 6 weeks from operative fixation. Given that orthopedic injury constitutes a significant proportion of traumatic injuries, and will likely continue to increase in number in the future, surgeons caring for patients with orthopedic trauma must be able to promptly recognize and manage sepsis secondary to orthopedic injury.

Mortality burden from variation in provision of surgical care in emergency general surgery: a cohort study using the National Inpatient Sample.

Background: The decision to undertake a surgical intervention for an emergency general surgery (EGS) condition (appendicitis, diverticulitis, cholecystitis, hernia, peptic ulcer, bowel obstruction, ischemic bowel) involves a complex consideration of factors, particularly in older adults. We hypothesized that identifying variability in the application of operative management could highlight a potential pathway to improve patient survival and outcomes. Methods: We included adults aged 65+ years with an EGS condition from the 2016-2017 National Inpatient Sample. Operative management was determined from procedure codes. Each patient was assigned a propensity score (PS) for the likelihood of undergoing an operation, modeled from patient and hospital factors: EGS diagnosis, age, gender, race, presence of shock, comorbidities, and hospital EGS volumes. Low and high probability for surgery was defined using a PS cut-off of 0.5. We identified two model-concordant groups (no surgery-low probability, surgery-high probability) and two model-discordant groups (no surgery-high probability, surgery-low probability). Logistic regression estimated the adjusted OR (AOR) of in-hospital mortality for each group. Results: Of 375 546 admissions, 21.2% underwent surgery. Model-discordant care occurred in 14.6%; 5.9% had no surgery despite a high PS and 8.7% received surgery with low PS. In the adjusted regression, model-discordant care was associated with significantly increased mortality: no surgery-high probability AOR 2.06 (1.86 to 2.27), surgery-low probability AOR 1.57 (1.49 to 1.65). Model-concordant care showed a protective effect against mortality (AOR 0.83, 0.74 to 0.92). Conclusions: Nearly one in seven EGS patients received model-discordant care, which was associated with higher mortality. Our study suggests that streamlined treatment protocols can be applied in EGS patients as a means to save lives. Level of evidence: III.

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.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Content and Accessibility of Surgical Critical Care Fellowship Websites in the United States.

BACKGROUND: Resident physicians are using the Internet to gather information about graduate medical education programs. The content of fellowship websites has been demonstrated to influence applicants' decisions. The purpose of this study was to evaluate the content of the surgical critical care fellowship (SCCF) program websites. METHODS: A list of Eastern Association for the Surgery of Trauma (EAST) and American Association for the Surgery of Trauma (AAST) SCCF programs was obtained, and compared to the Accreditation Council for Graduate Medical Education (ACGME) list of accredited programs. The accessibility of each website was assessed through Google®. Content areas were assessed for each SCCF website. RESULTS: At the time of this study, 76 SCCF were listed on the EAST website and an additional 14 were supplied by the AAST database. 125 programs were listed in the ACGME database. Of the 76 SCCF listed by EAST, 44 (58%), 32 (42%), and 7 (9%) of SCCF programs had an EAST listing that was 3, 5, or 10 years or more out of date, respectively. Of the 90 SCCF programs listed on EAST or AAST sites, 36 programs (40%) had an inaccurate PD named on their listing. One hundred and nineteen of the 125 (95%) SCCF programs had websites accessible through Google®. Only 25 (20%) programs had a website containing a program description, faculty list, curriculum, and current/past fellows list. CONCLUSIONS: Many SCCF websites lacked information regarding program specifics. Valuable information for potential applicants was inadequate across SCCF websites.

Time to early resuscitative intervention association with mortality in trauma patients at risk for hemorrhage.

BACKGROUND: Hemorrhage is the leading cause of preventable death after injury. Others have shown that delays in massive transfusion cooler arrival increase mortality, while prehospital blood product resuscitation can reduce mortality. Our objective was to evaluate if time to resuscitation initiation impacts mortality. METHODS: We combined data from the Prehospital Air Medical Plasma (PAMPer) trial in which patients received prehospital plasma or standard care and the Study of Tranexamic Acid during Air and ground Medical Prehospital transport (STAAMP) trial in which patients received prehospital tranexamic acid or placebo. We evaluated the time to early resuscitative intervention (TERI) as time from emergency medical services arrival to packed red blood cells, plasma, or tranexamic acid initiation in the field or within 90 minutes of trauma center arrival. For patients not receiving an early resuscitative intervention, the TERI was calculated based on trauma center arrival as earliest opportunity to receive a resuscitative intervention and were propensity matched to those that did to account for selection bias. Mixed-effects logistic regression assessed the association of 30-day and 24-hour mortality with TERI adjusting for confounders. We also evaluated a subgroup of only patients receiving an early resuscitative intervention as defined above. RESULTS: Among the 1,504 propensity-matched patients, every 1-minute delay in TERI was associated with 2% increase in the odds of 30-day mortality (adjusted odds ratio [aOR], 1.020; 95% confidence interval [CI], 1.006-1.033; p < 0.01) and 1.5% increase in odds of 24-hour mortality (aOR, 1.015; 95% CI, 1.001-1.029; p = 0.03). Among the 799 patients receiving an early resuscitative intervention, every 1-minute increase in TERI was associated with a 2% increase in the odds of 30-day mortality (aOR, 1.021; 95% CI, 1.005-1.038; p = 0.01) and 24-hour mortality (aOR, 1.023; 95% CI, 1.005-1.042; p = 0.01). CONCLUSION: Time to early resuscitative intervention is associated with morality in trauma patients with hemorrhagic shock. Bleeding patients need resuscitation initiated early, whether at the trauma center in systems with short prehospital times or in the field when prehospital time is prolonged. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Evaluation of critical care burden following traumatic injury from two randomized controlled trials.

Trauma resuscitation practices have continued to improve with new advances targeting prehospital interventions. The critical care burden associated with severely injured patients at risk of hemorrhage has been poorly characterized. We aim to describe the individual and additive effects of multiorgan failure (MOF) and nosocomial infection (NI) on delayed mortality and resource utilization. A secondary analysis of harmonized data from two large prehospital randomized controlled trials (Prehospital Air Medical Plasma (PAMPer) Trial and Study of Tranexamic Acid during Air and Ground Medical Prehospital Transport (STAAMP) Trial) was conducted. Only those patients who survived beyond the first 24 hours post-injury and spent at least one day in the ICU were included. Patients were stratified by development of MOF only, NI only, both, or neither and diagnosis of early (≤ 3 days) versus late MOF (> 3 days). Risk factors of NI and MOF, time course of these ICU complications, associated mortality, and hospital resource utilization were evaluated. Of the 869 patients who were enrolled in PAMPer and STAAMP and who met study criteria, 27.4% developed MOF only (n = 238), 10.9% developed NI only (n = 95), and 15.3% were diagnosed with both MOF and NI (n = 133). Patients developing NI and/or MOF compared to those who had an uncomplicated ICU course had greater injury severity, lower GCS, and greater shock indexes. Early MOF occurred in isolation, while late MOF more often followed NI. MOF was associated with 65% higher independent risk of 30-day mortality when adjusting for cofounders (OR 1.65; 95% CI 1.04-2.6; p = 0.03), however NI did not significantly affect odds of mortality. NI was individually associated with longer mechanical ventilation, ICU stay, hospital stay, and rehabilitation requirements, and the addition of MOF further increased the burden of inpatient and post-discharge care. MOF and NI remain common complications for those who survive traumatic injury. MOF is a robust independent predictor of mortality following injury in this cohort, and NI is associated with higher resource utilization. Timing of these ICU complications may reveal differences in pathophysiology and offer targets for continued advancements in treatment.