Introduction: Historically, hemorrhage has been attributed as the leading cause (40%) of early death. However, a rigorous, real-time classification of the cause of death (COD) has not been performed. This study sought to prospectively adjudicate and classify COD to determine the epidemiology of trauma mortality. Methods: 18 trauma centers prospectively enrolled all adult trauma patients at the time of death during 12/2015-8/2017. Immediately following death, attending providers adjudicated the primary and contributing secondary COD using standardized definitions. Data were confirmed by autopsies, if performed. Results: 1536 patients were enrolled with a median age of 55 (IQR 32-75). 74.5% were male. Penetrating mechanism (n=412) patients were younger (32 vs 64, p<0.0001) and more likely male (86.7% vs. 69.9%, p<0.0001). Falls were the most common mechanism of injury (26.6%), with GSWs second (24.3%). The most common overall primary COD was TBI (45%), followed by exsanguination (23%). TBI was non-survivable in 82.2% of cases. Blunt patients were more likely to have TBI (47.8% vs. 37.4%, p<0.0001) and penetrating patients exsanguination (51.7% vs 12.5%, p<0.0001) as the primary COD. Exsanguination was the predominant prehospital (44.7%) and early COD (39.1%) with TBI most common later. Penetrating mechanism patients died earlier with 80.1% on day 0 (vs. 38.5%, p<0.0001). Most deaths were deemed disease related (69.3%), rather than by limitation of further aggressive care (30.7%). Hemorrhage was a contributing cause to 38.8% of deaths that occurred due to withdrawal of care. Conclusions: Exsanguination remains the predominant early primary COD with TBI accounting for most deaths at later time points. Timing and primary COD vary significantly by mechanism. Contemporaneous adjudication of COD is essential to elucidate the true understanding of patient outcome, center performance, and future research.

BackgroundRecent studies have demonstrated the vital influence of commensal microbial communities on human health. The central role of the gut in the response to injury is well described; however, no prior studies have used culture-independent profiling techniques to characterize the gut microbiome after severe trauma. We hypothesized that in critically injured patients, the gut microbiome would undergo significant compositional changes in the first 72 hours after injury.MethodsTrauma stool samples were prospectively collected via digital rectal examination at the time of presentation (0 hour). Patients admitted to the intensive care unit (n=12) had additional stool samples collected at 24 hours and/or 72 hours. Uninjured patients served as controls (n=10). DNA was extracted from stool samples and 16S rRNA-targeted PCR amplification was performed; amplicons were sequenced and binned into operational taxonomic units (OTUs; 97% sequence similarity). Diversity was analyzed using principle coordinates analyses, and negative binomial regression was used to determine significantly enriched OTUs.ResultsCritically injured patients had a median Injury Severity Score of 27 and suffered polytrauma. At baseline (0 hour), there were no detectable differences in gut microbial community diversity between injured and uninjured patients. Injured patients developed changes in gut microbiome composition within 72 hours, characterized by significant alterations in phylogenetic composition and taxon relative abundance. Members of the bacterial orders Bacteroidales, Fusobacteriales and Verrucomicrobiales were depleted during 72 hours, whereas Clostridiales and Enterococcus members enriched significantly.DiscussionIn this initial study of the gut microbiome after trauma, we demonstrate that significant changes in phylogenetic composition and relative abundance occur in the first 72 hours after injury. This rapid change in intestinal microbiota represents a critical phenomenon that may influence outcomes after severe trauma. A better understanding of the nature of these postinjury changes may lead to the ability to intervene in otherwise pathological clinical trajectories.Level of evidenceIIIStudy typePrognostic/epidemiological

STRUCTURED ABSTRACT BACKGROUND Acute respiratory distress syndrome (ARDS) is common after Traumatic Brain Injury (TBI) and is associated with worse neurologic outcomes and longer hospitalization. However, the incidence and associated causes of ARDS in isolated TBI have not been well studied. METHODS We performed a subgroup analysis of 210 consecutive patients with isolated severe TBI enrolled in a prospective observational cohort at a Level 1 Trauma Center between 2005 and 2014. Subjects required endotracheal intubation and had isolated severe TBI defined by an Abbreviated Injury Score (AIS) Head ≥3 and AIS <3 in all other categories. ARDS within the first 8 days of admission was rigorously adjudicated using Berlin Criteria. Regression analyses were used to test the association between predictors of interest and ARDS. RESULTS The incidence of ARDS in the first eight days after severe isolated TBI was 30%. Patients who developed ARDS were administered more crystalloids (4.3 vs. 3.5 L, p= 0.005) and blood products in the first 12 hours of admission. Patients with ARDS had significantly worse clinical outcomes measured at 28 days, including longer median lengths of ICU and hospital stays (4 vs. 13 days, p<0.001, and 7.5 vs. 14.5 days, p<0.001, respectively). In unadjusted logistic regression analyses, the odds of developing ARDS were significantly associated with AIS Head score (OR 1.8, p=0.018), male sex (OR 2.9, p=0.012), and early transfusion of platelets 2.8 (p=0.003). These associations were similar in a multivariate logistic regression model. CONCLUSIONS In the era of balanced hemostatic resuscitation practices, severity of head injury, male sex, early crystalloids and early transfusion of platelets are associated with a higher risk of ARDS after severe isolated TBI. Early transfusion of platelets after severe TBI may be a modifiable risk factor for ARDS, and these findings invite further investigation into causal mechanisms driving this observed association. LEVEL OF EVIDENCE Level III; Epidemiologic