Eric M. Campion

Preinjury alcohol exposure attenuates the neuroinflammatory response to traumatic brain injury

BACKGROUND Traumatic brain injury (TBI) initiates a neuroinflammatory response that increases the risk of TBI-related mortality. Acute alcohol intoxication at the time of TBI is associated with improved survival. Ethanol is recognized as a systemic immunomodulator that may also impart neuroprotection. The effects of alcohol on TBI-induced neuroinflammation, however, are unknown. We hypothesized that ethanol treatment prior to TBI may provide neuroprotection by diminishing the neuroinflammatory response to injury. MATERIALS AND METHODS Mice underwent gavage with ethanol (EtOH) or water (H2O) prior to TBI. Animals were subjected to blunt TBI or sham injury (Sham). Posttraumatic rapid righting reflex (RRR) and apnea times were assessed. Cerebral and serum samples were analyzed by ELISA for inflammatory cytokine levels. Serum neuron-specific enolase (NSE), a biomarker of injury severity, was also measured. RESULTS Neurologic recovery from TBI was more rapid in H2O-treated mice compared with EtOH-treated mice. However, EtOH/TBI mice had a 4-fold increase in RRR time compared with EtOH/Sham, whereas H2O/TBI mice had a 15-fold increase in RRR time compared with H2O/Sham. Ethanol intoxication at the time of TBI significantly increased posttraumatic apnea time. Preinjury EtOH treatment was associated with reduced levels of proinflammatory cytokines IL-6, KC, MCP-1, and MIP-1α post TBI. NSE was significantly increased post injury in the H2O/TBI group compared with H2O/Sham but was not significantly reduced by EtOH pretreatment. CONCLUSIONS Alcohol treatment prior to TBI reduces the local neuroinflammatory response to injury. The decreased neurologic and inflammatory impact of TBI in acutely intoxicated patients may be responsible for improved clinical outcomes.

Preperitoneal pelvic packing reduces mortality in patients with life-threatening hemorrhage due to unstable pelvic fractures

BACKGROUND A 2015 American Association for the Surgery of Trauma trial reported a 32% mortality for pelvic fracture patients in shock. Angioembolization (AE) is the most common intervention; the Maryland group revealed time to AE averaged 5 hours. The goal of this study was to evaluate the time to intervention and outcomes of an alternative approach for pelvic hemorrhage. We hypothesized that preperitoneal pelvic packing (PPP) results in a shorter time to intervention and lower mortality. METHODS In 2004, we initiated a PPP protocol for pelvic fracture hemorrhage. RESULTS During the 11-year study, 2,293 patients were admitted with pelvic fractures; 128 (6%) patients underwent PPP (mean age, 44 ± 2 years; Injury Severity Score (ISS), 48 ± 1.2). The lowest emergency department systolic blood pressure was 74 mm Hg and highest heart rate was 120. Median time to operation was 44 minutes and 3 additional operations were performed in 109 (85%) patients. Median RBC transfusions before SICU admission compared with the 24 postoperative hours were 8 versus 3 units (p < 0.05). After PPP, 16 (13%) patients underwent AE with a documented arterial blush. Mortality in this high-risk group was 21%. Death was due to brain injury (9), multiple organ failure (4), pulmonary or cardiac failure (6), withdrawal of support (4), adverse physiology (3), and Mucor infection (1). Of those patients with physiologic exhaustion, 2 died in the operating room at 89 and 100 minutes after arrival, whereas 1 died 9 hours after arrival. CONCLUSIONS PPP results in a shorter time to intervention and lower mortality compared with modern series using AE. Examining mortality, only 3 (2%) deaths were attributed to the immediate sequelae of bleeding with physiologic failure. With time to death under 100 minutes in 2 patients, AE is unlikely to have been feasible. PPP should be used for pelvic fracture–related bleeding in the patient who remains unstable despite initial transfusion. LEVEL OF EVIDENCE Therapeutic study, level IV.

Implementation of a military-derived damage-control resuscitation strategy in a civilian trauma center decreases acute hypoxia in massively transfused patients

BACKGROUND Recent military experience supports a paradigm shift in shock resuscitation to damage-control resuscitation (DCR), which emphasizes a plasma-rich and crystalloid-poor approach to resuscitation. The effect of DCR on hypoxia after massive transfusion is unknown. We hypothesized that implementation of a military-derived DCR strategy in a civilian setting would lead to decreased acute hypoxia. METHODS A DCR strategy was implemented in 2007. We retrospectively reviewed patients receiving trauma surgeon operative intervention and 10 or more units of packed red blood cells (pRBCs) within 24 hours of injury at an adult Level I trauma center from 2001 to 2010. Demographic data, blood requirements, and PaO2/FIO2 ratios were analyzed. To evaluate evolving resuscitation strategies, we fit linear trend models to continuous variables and tested their slopes for statistical significance. RESULTS Two hundred sixteen patients met the study criteria, with a mean age of 35 ± 1.1 years and Injury Severity Score (ISS) of 31 ± 9.0. Of the patients, 80% were male, and 52% sustained penetrating injuries. Overall mortality was 32%. Overall mean pRBC and fresh frozen plasma (FFP) units infused in 24 hours were 23.2 ± 1.1 and 18.6 ± 1.1, respectively. Trends for patient age, sex, mechanism of injury, ISS, highest positive end-expiratory pressure, and mean total pRBC transfused over 24 hours were not statistically different from zero. An increasing trend in FFP and platelets transfused during the first 24 hours (p < 0.0001, p = 0.04, respectively) and a decrease in the pRBC/FFP ratio (p < 0.0001) were found. The amount of crystalloid infused during the initial 24 hours decreased with time (p < 0.0001). The lowest PaO2/FIO2 ratio recorded during the initial 24 hours increased during the study period (p = 0.01), indicating a statistically significant reduction in hypoxia. CONCLUSION A military-derived DCR strategy can be implemented in the civilian setting. DCR led to significant increases in FFP transfusion, decreases in crystalloid use, and acute hypoxia. LEVEL OF EVIDENCE Therapeutic study, level IV.

Resuscitation with washed aged packed red blood cell units decreases the proinflammatory response in mice after hemorrhage.

BACKGROUND Resuscitation with blood products instead of crystalloid in the treatment of hemorrhagic shock has been associated with improved outcomes in trauma patients requiring massive transfusions and transfusion of fresh products results in reduced morbidity and mortality compared with aged blood. Processes to eliminate harmful components of aged blood are under investigation. We hypothesized that washing blood would reduce levels of proinflammatory mediators in stored units, and resuscitation with washed units would attenuate the proinflammatory response in mice after hemorrhagic shock. METHODS Mice underwent pressure-controlled hemorrhage and resuscitation with fresh packed red blood cells (pRBCs) or 15-day-old washed or unwashed pRBCs. Cytokine concentrations in donor samples and recipient serum were measured. In addition, cytokine concentrations were measured in 15-day-old units that underwent three interval washes versus one poststorage wash. RESULTS Blood stored for 15 days demonstrated increased levels of interleukin 1&agr;, keratinocyte chemoattractant, macrophage inflammatory protein 1&agr;, and macrophage inflammatory protein 2 compared with fresh units. Washing 15-day-old pRBCs reduced concentrations of these cytokines. Cytokine levels in stored units that underwent multiple washes versus a single wash were not different. Mice resuscitated with 15-day-old unwashed pRBCs had increased levels of serum cytokines compared with mice resuscitated with fresh and 15-day-old washed pRBCs. CONCLUSION Aged pRBC units have elevated levels of proinflammatory cytokines compared with fresh units, and washing aged units after storage reduces cytokine concentrations. Resuscitation with washed units blunts the proinflammatory response in mice after hemorrhage. Washing aged pRBCs may improve the safety profile of aged units and may result in improved outcomes in subjects after hemorrhagic shock and resuscitation.

Recent developments in the assessment of the multiply injured trauma patient.

Purpose of reviewTo provide an update on the recent developments and controversies in the assessment of the traumatically injured patient. Recent findingsRecent literature suggests that: whole-body computed tomography (CT) is an effective strategy in more severely injured blunt trauma patients; 64-slice CT scanning now provides an effective noninvasive screening method for blunt cerebrovascular injury; the need for MRI imaging, in addition to CT, for the diagnosis of occult ligamentous injury of the cervical spine remains an unresolved controversy; point-of-care testing has made significant improvements in our ability to predict which patients will need a massive transfusion; and thromboelastography has enhanced our ability to tailor a hemostatic resuscitation more accurately. SummaryThe recent advances in the assessment of the multiply injured patient allow clinicians to more efficiently diagnose a patients injuries and implement treatment in a more timely manner.

Reconsidering the Resources Needed for Multiple Casualty Events: Lessons Learned From the Crash of Asiana Airlines Flight 214.

IMPORTANCE To date, a substantial portion of multiple casualty incident literature has focused exclusively on prehospital and emergency department resources needed for optimal disaster response. Thus, inpatient resources required to care for individuals injured in multiple casualty events are not well described. OBJECTIVE To highlight the resources beyond initial emergency department triage needed for multiple casualty events, using one of the largest commercial aviation disasters in modern US history as a case study. DESIGN, SETTING, AND PARTICIPANTS Prospective case series of injured individuals treated at an urban level I trauma center following the crash of Asiana Airlines flight 214 on July 6, 2013. This analysis was conducted between June 1, 2014, and December 1, 2015. EXPOSURE Commercial jetliner crash. MAIN OUTCOMES AND MEASURES Medical records, imaging data, nursing overtime, blood bank records, and trauma registry data were analyzed. Disaster logs, patient injuries, and blood product data were prospectively collected during the incident. RESULTS Among 307 people aboard the flight, 192 were injured; 63 of the injured patients were initially evaluated at San Francisco General Hospital and Trauma Center (the highest number at any of the receiving medical facilities; age range, 4-74 years [23 were aged <17 years and 3 were aged >60 years]; median injury severity score of 19 admitted patients, 9 [range, 9-45]), including the highest number of critically injured patients (10 of 12). Despite the high impact of the crash, only 3 persons (<1%) died, including 1 in-hospital death. Among the 63 patients, 32 (50.8%) underwent a computed tomographic imaging study, with imaging of the abdomen and pelvis being the most common. Sixteen of the 32 patients undergoing computed tomography (50.0%) had a positive finding on at least 1 scan. Nineteen patients had major injuries and required admission, with 5 taken directly from the emergency department to the operating room. The most frequent injury was spinal fracture (13 patients). In the first 48 hours, 15 operations were performed and 117 total units of blood products were transfused. A total of 370 nursing overtime hours were required to treat the injured patients on the day of the event. CONCLUSIONS AND RELEVANCE Proper disaster preparedness requires attention to hospital-level needs beyond initial emergency department triage. The Asiana Airlines flight 214 crash highlights the need to plan for high use of advanced imaging, blood products, operating room availability, nursing resources, and management of inpatient hospital beds.

Discovering the truth about life after discharge: long-term trauma related mortality

BACKGROUND Outcome after traumatic injury has typically been limited to the determination at time of discharge or brief follow-up. This study investigates the natural history of long-term survival after trauma. METHODS All highest-level activation patients prospectively enrolled in an ongoing cohort study from 2005 to 2012 were selected. To allow for long-term follow-up, patients had to be enrolled at least 1 year before the latest available data from the National Death Index (NDI, 2013). Time and cause of mortality was determined based on death certificates. Survival status was determined by the latest date of either care in our institution or NDI query. Kaplan-Meier curves were created stratified for Injury Severity Score (ISS). Survival was compared with estimated actuarial survival based on age, sex, and race. RESULTS A total of 908 highest-level activation patients (median ISS, 18) were followed up for a median 1.7 years (interquartile range 1.0–2.9; maximum, 9.8 years). Survival data were available on 99.8%. Overall survival was 73% (663 of 908). For those with at least 2-year follow-up, survival was only 62% (317 of 509). Severity of injury predicted long-term survival (p < 0.0001) with those having ISS of 25 or greater with the poorest outcome (57% survival at 5 years). For all ISS groups, survival was worse than predicted actuarial survival (p < 0.001). When excluding early deaths (⩽30 days), observed survival was still significantly lower than estimated actuarial survival (p < 0.002). Eighteen percent (44 of 245 deaths) of all deaths occurred after 30 days. Among late deaths, 53% occurred between 31 days and 1 year after trauma. Trauma-related mortality was the leading cause of postdischarge death, accounting for 43% of the late deaths. CONCLUSION Postdischarge deaths represent a significant percentage of total trauma-related mortality. Despite having “survived” to leave the hospital, long-term survival was worse than predicted actuarial survival, suggesting that the mortality from injury does not end at “successful” hospital discharge. LEVEL OF EVIDENCE Prognostic study, level III.

Simulated aeromedical evacuation does not affect systemic inflammation or organ injury in a murine model of hemorrhagic shock.

Hemorrhagic shock is a primary injury amongst combat casualties. Aeromedical evacuation (AE) of casualties exposes patients to a hypobaric, hypoxic environment. The effect of this environment on the host response to hemorrhagic shock is unknown. In the present study, we sought to determine the effect of simulated AE on systemic inflammation and organ injury using a murine model of hemorrhagic shock. Mice underwent femoral artery cannulation and were hemorrhaged for 60 minutes. Mice were then resuscitated with a 1:1 ratio of plasma:packed red blood cells. At 1 or 24 hours after resuscitation, mice were exposed to a 5-hour simulated AE or remained at ground level (control). Serum was analyzed for cytokine concentrations and organs were assessed for neutrophil accumulation and vascular permeability. Mice in the simulated AE groups demonstrated reduced arterial oxygen saturation compared to ground controls. Serum cytokine concentrations, neutrophil recruitment, and vascular permeability in the lung, ileum, and colon in the simulated AE groups were not different from the ground controls. Our results demonstrate that mice exposed to simulated AE following hemorrhagic shock do not exhibit worsened systemic inflammation or organ injury compared to controls. The data suggest that AE has no adverse effect on isolated hemorrhagic shock.

Supplemental oxygen attenuates the increase in wound bacterial growth during simulated aeromedical evacuation in goats

BACKGROUND Bacterial growth in soft tissue and open fractures is a known risk factor for tissue loss and complications in contaminated musculoskeletal wounds. Current care for battlefield casualties with soft tissue and musculoskeletal wounds includes tactical and strategic aeromedical evacuation (AE). This exposes patients to a hypobaric, hypoxic environment. In this study, we sought to determine whether exposure to AE alters bacterial growth in contaminated complex musculoskeletal wounds and whether supplemental oxygen had any effect on wound infections during simulated AE. METHODS A caprine model of a contaminated complex musculoskeletal wound was used. Complex musculoskeletal wounds were created and inoculated with bioluminescent Pseudomonas aeruginosa. Goats were divided into three experimental groups: ground control, simulated AE, and simulated AE with supplemental oxygen. Simulated AE was induced in a hypobaric chamber pressurized to 8,800 feet for 7 hours. Bacterial luminescence was measured using a photon counting camera at three time points: preflight (20 hours postsurgery), postflight (7 hours from preflight and 27 hours postsurgery), and necropsy (24 hours from preflight and 44 hours postsurgery). RESULTS There was a significant increase in bacterial growth in the AE group compared with the ground control group measured postflight and at necropsy. Simulated AE induced hypoxia with oxygen saturation less than 93%. Supplemental oxygen corrected the hypoxia and significantly reduced bacterial growth in wounds at necropsy. CONCLUSIONS Hypoxia induced during simulated AE enhances bacterial growth in complex musculoskeletal wounds which can be prevented with the application of supplemental oxygen to the host.

Characterizing the gut microbiome in trauma: significant changes in microbial diversity occur early after severe injury

Background Recent 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. Methods Trauma 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. Results Critically 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. Discussion In 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 evidence III Study type Prognostic/epidemiological