Selective aortic arch perfusion with fresh whole blood or HBOC-201 reverses hemorrhage-induced traumatic cardiac arrest in a lethal model of noncompressible torso hemorrhage BACKGROUND Hemorrhage-induced traumatic cardiac arrest (HiTCA) has a dismal survival rate. Previous studies demonstrated selective aortic arch perfusion (SAAP) with fresh whole blood (FWB) improved the rate of return of spontaneous circulation (ROSC) after HiTCA, compared with resuscitative endovascular balloon occlusion of the aorta and cardiopulmonary resuscitation (CPR). Hemoglobin-based oxygen carriers, such as hemoglobin-based oxygen carrier (HBOC)-201, may alleviate the logistical constraints of using FWB in a prehospital setting. It is unknown whether SAAP with HBOC-201 is equivalent in efficacy to FWB, whether conversion from SAAP to extracorporeal life support (ECLS) is feasible, and whether physiologic derangement post-SAAP therapy is reversible. METHODS Twenty-six swine (79 ± 4 kg) were anesthetized and underwent HiTCA which was induced via liver injury and controlled hemorrhage. Following arrest, swine were randomly allocated to resuscitation using SAAP with FWB (n = 12) or HBOC-201 (n = 14). After SAAP was initiated, animals were monitored for a 20-minute prehospital period prior to a 40-minute damage control surgery and resuscitation phase, followed by 260 minutes of critical care. Primary outcomes included rate of ROSC, survival, conversion to ECLS, and correction of physiology. RESULTS Baseline physiologic measurements were similar between groups. ROSC was achieved in 100% of the FWB animals and 86% of the HBOC-201 animals (p = 0.483). Survival (t = 320 minutes) was 92% (11/12) in the FWB group and 67% (8/12) in the HBOC-201 group (p = 0.120). Conversion to ECLS was successful in 100% of both groups. Lactate peaked at 80 minutes in both groups, and significantly improved by the end of the experiment in the HBOC-201 group (p = 0.001) but not in the FWB group (p = 0.104). There was no significant difference in peak or end lactate between groups. CONCLUSION Selective aortic arch perfusion is effective in eliciting ROSC after HiTCA in a swine model, using either FWB or HBOC-201. Transition from SAAP to ECLS after definitive hemorrhage control is feasible, resulting in high overall survival and improvement in lactic acidosis over the study period.

Four-factor prothrombin complex concentrate is associated with improved survival in trauma-related hemorrhage: A nationwide propensity-matched analysis INTRODUCTION Post-traumatic hemorrhage is the most common preventable cause of death in trauma. Numerous small single-center studies have shown the superiority of four-factor prothrombin complex concentrate (4-PCC) along with fresh frozen plasma (FFP) over FFP alone in resuscitation of trauma patients. The aim of our study was to evaluate outcomes of severely injured trauma patients who received 4-PCC + FFP compared to FPP alone. METHODS Two-year (2015–2016) analysis of the American College of Surgeons-Trauma Quality Improvement Program database. All adult (age ≥18 years) trauma patients who received 4-PCC + FFP or FFP alone were included. We excluded patients who were on preinjury anticoagulants. Patients were stratified into two groups: 4-PCC + FFP versus FFP alone and were matched in a 1:1 ratio using propensity score matching for demographics, vitals, injury parameters, comorbidities, and level of trauma centers. Outcome measures were packed red blood cells, plasma and platelets transfused, complications, and mortality. RESULTS A total of 468 patients (4-PCC + FFP, 234; FFP alone, 234) were matched. Mean age was 50 ± 21 years; 70% were males; median injury severity score was 27 [20–36], and 86% had blunt injuries. Four-PCC + FFP was associated with a decreased requirement for packed red blood cells (6 units vs. 10 units; p = 0.02) and FFP (3 units vs. 6 units; p = 0.01) transfusion compared to FFP alone. Patients who received 4-PCC + FFP had a lower mortality (17.5% vs. 27.7%, p = 0.01) and lower rates of acute respiratory distress syndrome (1.3% vs. 4.7%, p = 0.04) and acute kidney injury (2.1% vs. 7.3%, p = 0.01). There was no difference in the rates of deep venous thrombosis (p = 0.11) and pulmonary embolism (p = 0.33), adverse discharge disposition (p = 0.21), and platelets transfusion (p = 0.72) between the two groups. CONCLUSIONS Our study demonstrates that the use of 4-PCC as an adjunct to FFP is associated with improved survival and reduction in transfusion requirements compared to FFP alone in resuscitation of severely injured trauma patients. Further studies are required to evaluate the role of addition of PCC to the massive transfusion protocol. LEVEL OF EVIDENCE Therapeutic studies, level III.

Effect of damage control laparotomy on major abdominal complications and lengths of stay: A propensity score matching and Bayesian analysis BACKGROUND In patients for whom surgical equipoise exists for damage control laparotomy (DCL) and definitive laparotomy (DEF), the effect of DCL and its associated resource utilization are unknown. We hypothesized that DEF would be associated with fewer abdominal complications and less resource utilization. METHODS In 2016, six US Level I trauma centers performed a yearlong, prospective, quality improvement project with the primary aim to safely decrease the use of DCL. From this cohort of patients undergoing emergent trauma laparotomy, those who underwent DCL but were judged by majority faculty vote at each center to have been candidates for potential DEF (pDEF) were prospectively identified. These pDEF patients were matched 1:1 using propensity scoring to the DEF patients. The primary outcome was the incidence of major abdominal complications (MAC). Deaths within 5 days were excluded. Outcomes were assessed using both Bayesian generalized linear modeling and negative binomial regression. RESULTS Eight hundred seventy-two total patients were enrolled, 639 (73%) DEF and 209 (24%) DCL. Of the 209 DCLs, 44 survived 5 days and were judged to be patients who could have safely been closed at the primary laparotomy. Thirty-nine pDEF patients were matched to 39 DEF patients. There were no differences in demographics, mechanism of injury, Injury Severity Score, prehospital/emergency department/operating room vital signs, laboratory values, resuscitation, or procedures performed during laparotomy. There was no difference in MAC between the two groups (31% DEF vs. 21% pDEF, relative risk 0.99, 95% credible interval 0.60–1.54, posterior probability 56%). Definitive laparotomy was associated with a 72%, 77%, and 72% posterior probability of more hospital-free, intensive care unit-free, and ventilator-free days, respectively. CONCLUSION In patients for whom surgeons have equipoise for DCL versus definitive surgery, definitive abdominal closure was associated with a similar probability of MAC, but a high probability of fewer hospital-free, intensive care unit-free, and ventilator-free days. LEVEL OF EVIDENCE Therapeutic/care management, level III.

Top-tier emergency general surgery hospitals: Good at one operation, good at them all BACKGROUND There is a longstanding interest in the field of management science to study high performance organizations. Applied to medicine, research on hospital performance indicates that some hospitals are high performing, while others are not. The objective of this study was to identify a cluster of high-performing emergency general surgery (EGS) hospitals and assess whether high performance at one EGS operation was associated with high performance on all EGS operations. METHODS Adult patients who underwent one of eight EGS operations were identified in the California State Inpatient Database (2010–2011), which we linked to the American Hospital Association database. Beta regression was used to estimate a hospital's risk-adjusted mortality, accounting for patient- and hospital-level factors. Centroid cluster analysis grouped hospitals by patterns of mortality rates across the eight EGS operations using z scores. Multinomial logistic regression compared hospital characteristics by cluster. RESULTS A total of 220 acute care hospitals were included. Three distinct clusters of hospitals were defined based on assessment of mortality for each operation type: high-performing hospitals (n = 66), average performing (n = 99), and low performing (n = 55). The mortality by individual operation type at the high-performing cluster was consistently at least 1.5 standard deviations better than the low-performing cluster (p < 0.001). Within-cluster variation was minimal at high-performing hospitals compared with wide variation at low-performing hospitals. A hospital's high performance in one EGS operation type predicted high performance on all EGS operation types. CONCLUSION High-performing EGS hospitals attain excellence across all types of EGS operations, with minimal variability in mortality. Poor-performing hospitals are persistently below average, even for low-risk operations. These findings suggest that top-performing EGS hospitals are highly reliable, with systems of care in place to achieve consistently superior results. Further investigation and collaboration are needed to identify the factors associated with high performance. LEVEL OF EVIDENCE Prognostic, level III.

Evaluating mortality outlier hospitals to improve the quality of care in emergency general surgery BACKGROUND Expected performance rates for various outcome metrics are a hallmark of hospital quality indicators used by Agency of Healthcare Research and Quality, Center for Medicare and Medicaid Services, and National Quality Forum. The identification of outlier hospitals with above- and below-expected mortality for emergency general surgery (EGS) operations is therefore of great value for EGS quality improvement initiatives. The aim of this study was to determine hospital variation in mortality after EGS operations, and compare characteristics between outlier hospitals. METHODS Using data from the California State Inpatient Database (2010–2011), we identified patients who underwent one of eight common EGS operations. Expected mortality was obtained from a Bayesian model, adjusting for both patient- and hospital-level variables. A hospital-level standardized mortality ratio (SMR) was constructed (ratio of observed to expected deaths). Only hospitals performing three or more of each operation were included. An “outlier” hospital was defined as having an SMR with 80% confidence interval that did not cross 1.0. High- and low-mortality SMR outliers were compared. RESULTS There were 140,333 patients included from 220 hospitals. Standardized mortality ratio varied from a high of 2.6 (mortality, 160% higher than expected) to a low of 0.2 (mortality, 80% lower than expected); 12 hospitals were high SMR outliers, and 28 were low SMR outliers. Standardized mortality was over three times worse in the high SMR outliers compared with the low SMR outliers (1.7 vs. 0.5; p < 0.001). Hospital-, patient-, and operative-level characteristics were equivalent in each outlier group. CONCLUSION There exists significant hospital variation in standardized mortality after EGS operations. High SMR outliers have significant excess mortality, while low SMR outliers have superior EGS survival. Common hospital-level characteristics do not explain the wide gap between underperforming and overperforming outlier institutions. These findings suggest that SMR can help guide assessment of EGS performance across hospitals; further research is essential to identify and define the hospital processes of care which translate into optimal EGS outcomes. LEVEL OF EVIDENCE Epidemiologic Study, level III.

Ventilator-associated events, not ventilator-associated pneumonia, is associated with higher mortality in trauma patients BACKGROUND Ventilator-associated events (VAE), using objective diagnostic criteria, are the preferred quality indicator for patients requiring mechanical ventilation (MV) for greater than 48 hours. We aim to identify the occurrence of VAE in our trauma population, the impact on survival, and length of stay, as compared to the traditional definition of ventilator-associated pneumonia (VAP). METHODS This retrospective review included adult trauma patients, who were Washington residents, admitted between 2012 and 2017, and required at least 3 days of MV. Exclusions included patients with Abbreviated Injury Scale head score greater than 4 and burn related mechanisms of injury. We matched trauma registry data with our institutional, physician-adjudicated, and culture-confirmed ventilator event database. We compared the clinical outcomes of ventilator-free days, intensive care unit length of stay, hospital length of stay, and likelihood of death between VAE and VAP. RESULTS One thousand five hundred thirty-three trauma patients met criteria; 124 (8.1%) patients developed VAE, 114 (7.4%) patients developed VAP, and 63 (4.1%) patients met criteria for both VAE and VAP. After adjusted analyses, patients with VAE were more likely to die (hazard ratio [HR], 2.86; 95% confidence interval [CI], 1.44–5.68), than those with VAP, as well those patients with neither diagnosis (HR, 2.83; 95% CI, 1.83–4.38). Patients with VAP were no more likely to die (HR, 1.55; 95% CI, 0.91–2.68) than those with neither diagnosis. Patients with VAE had fewer ventilator-free days than those with VAP (HR, −2.71; 95% CI, −4.74 to −0.68). CONCLUSION Critically injured trauma patients who develop VAE are three times more likely to die and utilize almost 3 days more MV than those that develop VAP. The objective criteria of VAE make it a promising indicator on which quality indicator efforts should be focused. Future studies should be aimed at identification of modifiable risk factors for VAE and their impact on outcome, as these patients are at high risk for death. LEVEL OF EVIDENCE Retrospective cohort study, level III.

Trauma system resource preservation: A simple scene triage tool can reduce helicopter emergency medical services overutilization in a state trauma system BACKGROUND Helicopter emergency medical services improve survival in some injured patients but current utilization leads to significant overtriage with considerable numbers of transported patients discharged home from the emergency department or found to have non–time-sensitive injuries. Current triage models for utilization are complex and untested. METHODS Data from a state trauma registry were reviewed from 1987 to 1993 and from 2013 to 2015 and compared. Data from 2013 to 2015 were analyzed for field information found to influence mortality and a model for low mortality-risk patients designed. RESULTS Indexed to population, a major increase in numbers of injured patients transported directly to designated trauma centers (39.849–167.626/100,000/year) occurred with an increased portion transported by helicopter emergency medical services from 7.28% to 9.26%. A simple triage tool to predict low mortality rates was designed utilizing results from logistic regression. Nongeriatric adult patients (age, 16.0–69.9 years) with a blunt injury mechanism, normal Glasgow Coma Scale motor score, pulse rate of 60 bpm to 120 bpm and respiratory rate of 10 breaths per minute to 29 breaths per minute are at low risk for mortality. Cost for helicopter transportation was substantially higher than ground transportation based on available data. Cost differentials in transport mode increased patient financial risk when helicopter transportation was utilized. CONCLUSION Implementing a simple decision tool designating nongeriatric adult patients with a blunt injury mechanism, normal Glasgow Coma Scale motor score, systolic blood pressure greater than 90 mm Hg, pulse rate of 60 bpm to 120 bpm, and respiratory rate of 10 breaths per minute to 29 breaths per minute to ground transportation would result in substantial savings without an increase in mortality and reduce risk of patient financial harm. LEVEL OF EVIDENCE Prognostic/Epidemiological study, level IV. Economic and value based evaluation, level IV.

Acute resuscitation with polyethylene glycol-20k: A thromboelastographic analysis BACKGROUND Previous ex vivo studies have shown that polyethylene glycol-20,000 Da (PEG-20k), a novel synthetic polymer that is highly effective for resuscitation, has a hypocoagulable effect on human blood. This study's objective was to determine the in vivo effects of PEG-20k-based resuscitation solutions on coagulation and platelet function in a porcine model of hemorrhagic shock. METHODS Anesthetized pigs underwent controlled hemorrhage until the lactate reached 7 mmol/L or 50% to 55% of their estimated blood volume was removed. A laparotomy was performed to simulate tissue injury. Low volume resuscitation (LVR) was given with fluorescein isothiocyanate-labeled 10% PEG-20k solution (100 mg/mL) or Lactated Ringers, both delivered at volumes equal to 10% of the estimated blood volume (n = 5). Thromboelastography was performed after surgery (baseline), after hemorrhage, and 15 minutes, 120 minutes, and 240 minutes postresuscitation. Hemoglobin was measured to determine changes in plasma volume. Plasma PEG-20k concentration was measured by indicator dilution. RESULTS Pigs given PEG-20k survived 2.6-fold longer than controls (p < 0.001) and had a significant increase in plasma volume demonstrated by the sustained drop in hemoglobin, relative to controls. Pigs resuscitated with LR died from hypotension an average of 90 minutes after resuscitation compared to the PEG-20k pigs, which all survived 240 minutes and were then euthanized with normal blood pressure and lactate. Administration of PEG-20k primarily decreased the thromboelastograph maximum amplitude, however this began to return toward baseline by 240 minutes. Peak plasma concentration of PEG-20k after LVR were 40% lower than predicted, based on simple dilution (5.7 mg/mL vs. 10 mg/mL) and the half-life was 59.6 minutes. CONCLUSION These data demonstrate that acute resuscitation with PEG-20k significantly improves tolerance to hypovolemia but also decreases platelet function in the coagulation cascade, which was due, in part, to its volume expanding effects.

Comparison of male and female victims of intimate partner homicide and bidirectionality—an analysis of the national violent death reporting system BACKGROUND Intimate partner violence (IPV) is a public health crisis, affecting at least 1:4 women and 1:9 men. A recent multicenter trial on universal screening in trauma patients showed similar rates of positive screens between men and women. Few studies have explored the bidirectional violence in opposite-sex or same-sex relationships. Our goal was to estimate prevalence and risk factors for the most severe manifestation of IPV: intimate partner homicide. METHODS This is a 2003–2015 retrospective review of the National Violent Death Reporting System, a Centers for Disease Control and Prevention database of surveillance data. Deaths were coded IPV if the primary relationship between the suspect and victim fell into the categories of current partner or ex-partner. Bivariable and multivariable analysis examined differences between groups for factors and circumstances. RESULTS A total of 6,131 persons in opposite-sex relationships and 181 in same-sex relationships were murdered as a result of IPV. Women and Black men were disproportionately affected, and alcohol and preceding arguments were a factor in a higher proportion of male victims. Abuse preceded homicide in many women with almost half of male suspects attempting or committing suicide at the time of intimate partner homicide. Women were more likely than men to use a stabbing instrument, although firearms were still the most common means for each group. In 46.5% of homicides of women, the male suspect attempted suicide (p < 0.001). Bidirectionality was highest in male victims of female perpetrators and in same-sex pairings regardless of sex of the victim. CONCLUSION Homicide caused by IPV is a significant public health crisis for both men and women, with women and Black men at particular risk. Firearms are the most commonly used weapon for homicide in both sexes, and mental illness is not a common risk factor. A staggering proportion of these homicides involve suicide of the suspect, suggesting that each potential incident has two victims to target for prevention and intervention. Interventional programs to prevent such bidirectional mortality are urgently needed. LEVEL OF EVIDENCE Retrospective secondary data analysis, level III.

Altered monocyte and NK cell phenotypes correlate with posttrauma infection BACKGROUND Trauma induces a complex immune response, requiring a systems biology approach to capture multicellular changes. Using mass cytometry by time-of-flight (CyTOF), we evaluated time-dependent changes in peripheral blood in trauma patients to identify changes correlated with infection. METHODS Total leukocytes were prepared via red blood cell lysis using peripheral blood samples from trauma patients with an Injury Severity Score greater than 20 at Days 1, 3, and 5 after injury, and from age- and sex-matched uninjured controls. Cells were stained using a 33-marker immunophenotyping CyTOF panel. Statistics were calculated using one-way analysis of variance with multiple comparisons. RESULTS The CyTOF staining demonstrated changes in many cell subsets. The mean expression intensity of CD86 on monocytes decreased significantly at all time points after injury. When the patients were stratified based on development of infection, there was a trend to decreased CD86 expression on monocytes of those patients that developed subsequent infection. Based on stratification, we identified significantly increased expression of CD39 on NK cells only in patients that developed an infection. CONCLUSION This study used a systems biology approach to identify novel changes in circulating immune cell subsets in trauma patients correlating with post-traumatic infection. Decreased expression of CD86, a costimulatory molecule, on monocytes demonstrates that trauma affects the innate system's ability to control T-cell immunity. We also found that CD39 expression on NK cells increased significantly in patients with subsequent infection. CD39 is a protein that generates adenosine, which has immunosuppressive effects on several immune cell types including NK cells. In summary, our results point to pathways that may be central to second-hit infections and further study to delineate these pathways could be key to generating clinical biomarkers or targeted immune therapies for trauma patients. LEVEL OF EVIDENCE Prognostic study, level II.