24.06 Hydrogen Sulfide Improves Resuscitation via Non-Hibernatory Mechanisms in a Porcine Shock Model

Posted on December 22, 2014

S. Satterly1, J. Stallings1, S. Salgar1, Z. Hoffer1, M. Martin1  1Madigan Army Medical Center,Surgery,Tacoma, WA, USA

Introduction: Hydrogen sulfide (H2S) has been demonstrated to induce a “suspended animation-like” state in rodent models by reversible inhibition of cellular respiration and marked metabolic suppression, and has been proposed as a potential pharmacologic adjunct to resuscitation from shock states. There is little data currently available about the mechanisms and efficacy of H2S in larger animals or humans. We examined H2S as a pharmacologic adjunct to resuscitation in a porcine model of severe traumatic shock.

Methods:  Twenty-one adult swine were assigned to 3 study arms: sham, H2S, and saline vehicle controls (SC). All pigs underwent laparotomy and instrumentation, and the 2 study arms then underwent a 35% controlled hemorrhage followed by 50 minutes of truncal ischemia via aortic cross-clamp. H2S (5mg/kg) or saline was administered immediately prior to reperfusion, followed by 6 hours of resuscitation. Resuscitation requirements, laboratory parameters, end-organ histology, and inflammatory/oxidative product gene expression (by rtPCR) were measured and compared between groups.

Results: All animals survived to the 6-hour post resuscitation time point. Both treatment arms demonstrated severe shock characterized by fluid and vasopressor requirements, metabolic acidosis, and hypotension compared to sham animals. Animals treated with H2S demonstrated significantly lower resuscitative requirements (total epinephrine 727 µg vs 3052 µg, p<0.05), decreased fluid requirements, and lower serum lactate levels (7 mmol/L vs 10 mmol/L) versus SC. Cardiac output was slightly decreased with H2S treatment but all other hemodynamic and metabolic parameters were equivalent between H2S and C groups. Serum liver and kidney biomarkers were unchanged, but administration of H2S was associated with a significant improvement in histopathologic liver and kidney injury scores compared to SC (see Figure, both p<0.05).   Both study groups demonstrated significantly increased gene expression of hypoxia inducible factor (HIF-1α), and nitric oxide synthase (eNOS, iNOS2, iNOS3) relative to sham animals. However, H2S was associated with increased expression of HIF-1α and decreased iNOS2 levels compared to SC.

Conclusion: Administration of H2S in a large animal model of severe traumatic shock resulted in a significant decrease in resuscitative requirements, decreased metabolic acidosis, and less end-organ histologic injury compared to standard resuscitation. H2S did not induce profound metabolic suppression as seen in rodents, and appears to have alternative mechanisms of action in large animals.

 

24.07 Selective Inhibition of PAD4 Improves Survival in a Rat Model of Lethal Hemorrhagic Shock

Posted on December 22, 2014

W. He1, P. Zhou1, Z. Chang1, B. Liu1, J. Maxwell1, I. Halaweish1, Y. Li1, H. B. Alam1  1University Of Michigan,General Surgery,Ann Arbor, MI, USA

Introduction: We have recently shown that inhibition of peptidylarginine deiminase (PAD) improves survival in a rodent model of lethal cecal ligation and puncture. However, the role of PAD inhibitor in hemorrhagic shock is largely unknown. The goal of this study was to investigate whether and how YW3-56, a selective PAD4 inhibitor, could improve survival following lethal hemorrhagic shock.

Methods: Anesthetized male Wistar-Kyoto rats (n=10/group) were subjected to 55% blood loss over 40 minutes (35% arterial hemorrhage in 10 minutes and 20% venous hemorrhage in 30 minutes), and randomized into three groups: (1) Dimethyl sulfoxide (DMSO) vehicle, (2) YW3-56 (10 mg/kg) in DMSO, and (3) Sham (no hemorrhage, no treatment). Survival was monitored for 24 h. In a second study, RAW 264.1 mouse macrophages were exposed to hypoxic conditions (0.5% O2, 5% CO2, and 94.5% N2) at 37°C in the presence or absence of YW3-56 (2.5 μM). The cells and cultured medium were harvested at 1, 3, and 6 hours. Sham (no hypoxia, no YW3-56) group served as a control.  Cell viability was determined by MTT assay. Enzyme-linked immunosorbent assay was performed to analyze the secreted tumor necrosis factor α (TNF-α) and interleukin (IL)-6 in the culture medium.

Results: Hemorrhage was associated with 100% mortality in the DMSO treated animals within 3 hours, whereas 57% of the YW3-56-treated animals survived over 24 hours (Fig 1A, p< 0.05). YW3-56 treatment also significantly increased the cellular viability in the hypoxic macrophages (Fig 1B, p<0.001). Moreover, hypoxic insult induced TNF-α and IL-6 secretion in the medium, which was significantly attenuated by YW3-56 treatment (p<0.05).

Conclusion: Our results demonstrate for the first time that administration of YW3-56 significantly improves survival in vivo and in vitro, and inhibits hypoxia-induced production of key pro-inflammatory cytokines.  

 

20.02 Optimal Timing of Tracheostomy for Prolonged Respiratory Failure after Blunt Trauma

Posted on December 22, 2014

J. E. Keenan1, B. C. Gulack1, D. P. Nussbaum1, C. Green1, M. L. Shapiro1, S. N. Vaslef1, J. E. Scarborough1  1Duke University Medical Center,Durham, NC, USA

Introduction: Controversy exists over when tracheostomy should be performed in the critically ill trauma patient with prolonged respiratory failure.  The purpose of this study was to determine the optimal timing of tracheostomy in this population using a large national data source.

Methods: The research data set of the National Trauma Data Bank (years 2008-2011) was used to identify a cohort of adult patients who required tracheostomy within the first 21 days of hospitalization after blunt trauma (with ISS ≥9) and who had been directly admitted to the ICU or operating room from the emergency department.  Patients who may have required tracheostomy for airway stabilization rather than prolonged respiratory failure were excluded, including those who underwent tracheostomy within 4 days from admission, those with head or neck injuries (defined as abbreviated injury scale ≥1), and those who spent less than one day in the ICU.  A restricted cubic spline analysis was performed to determine how timing of tracheostomy was associated with in-hospital mortality. The cohort was stratified based on the results of this analysis.  Unadjusted baseline demographics, characteristics, and outcomes were compared between groups. Multivariable logistic regression analysis was employed to evaluate the independent association of timing of tracheostomy with mortality after adjustment for age, gender, race, payor status, ACS trauma verification level, ISS, and emergency department GCS.

Results: 9,187 patients were included in the study.  Overall in-hospital mortality was 9.9% (n=899).  Based on restricted cubic spline analysis, probability of mortality appeared to be higher in patients who underwent tracheostomy prior to hospital day 11  (Figure). The cohort was therefore stratified into early and delayed tracheostomy groups based on whether the patient underwent tracheostomy before or on/after hospital day 11, respectively.  There were 5,121 (55.7%) patients in the early tracheostomy group, and 4,066 (44.3%) in the delayed tracheostomy group.  Prior to adjustment, the delayed tracheostomy group had a significantly decreased mortality compared to the early tracheostomy group (8.8% vs 10.7%, p=0.004).  Following adjustment with multivariable logistic regression, the delayed tracheostomy group continued to have significantly decreased odds of mortality compared to the early tracheostomy group (AOR: 0.83, 95% CI: 0.71-0.96).

Conclusion: This study of a large national cohort supports that delaying tracheostomy up to hospital day 11 provides survival benefit in patients with prolonged respiratory failure after blunt trauma.  Trauma surgeons and critical care physicians should therefore consider avoiding tracheostomy placement prior to this time point.
 

20.03 Thrombelastography is Superior to Trauma Scoring Systems as a Predictor of Massive Hemorrhage

Posted on December 22, 2014

D. Burneikas2, E. E. Moore1,2, M. P. Chapman2,3, H. B. Moore1,2, E. Gonzalez1,2, C. Silliman2,4, A. Banerjee2  1Denver Health Medical Center,Aurora, CO, USA 2University Of Colorado Denver,Aurora, CO, USA 3Georgia Health Sciences University,Augusta, GA, USA 4Children’s Hospital Colorado,Aurora, CO, USA

Introduction: Massive blood transfusion is required in roughly 3% of civilian and 8% of military trauma patients and requires mobilization of enormous hospital and personnel resources to administer. Thus, accurate prediction of the need for massive transfusion in severely injured trauma patients is highly desireable from both a logistical and patient outcome standpoint. To this end, numerous trauma scoring systems have been developed to predict massive transfusion, such as the Trauma-Associated Severe Hemorrhage (TASH) and Assesment of Blood Consumption (ABC) score. These scores are cumbersome to calculate in the chaotic setting of an emergent trauma, therefore we sought to determine if admission assessment of the patient's Rapid thrombelastogram (Rapid TEG) could provide an easier and more reliable predictive parameter for massive hemorrhage and transfusion. 

Methods:  61 consectutive trauma patients of our highest level of activation and deemed likely to require a massive transfusion by the attending surgeon received an admission Rapid TEG. Their ABC and TASH scores were calculated, as well as binary criteria based on the Resusciatation Outcomes Consortium vital sign inclusion criteria and our center's newly implemented MTP entrance trigger criteria. Reciever operating characteristic (ROC) plots were constructed for these scoring systems with respect to massive hemorrhage (defined as 10 or more units of PRBCS in the first 6 hours or death from massive hemorrhage prior to that time) as the binary outcome variable. ROC plots were also constructed for the Rapid TEG parameters: ACT, Alpha Angle, MA and LY30. Lastly, an ROC curve for Global TEG Assessment parameter was constructed based upon an abnormal finding in any of the three most specific TEG parameters for predicting massive hemorrhage (Alpha Angle, MA and LY30) in order to reflect the TEG tracing as a whole. The merits of these various predictive methodologies were compared according the area under their respective ROC curves.

Results: The area under the ROC curves for the scoring systems was generally very poor (ABC 0.50, TASH: 0.58) and the vital sign and MTP criteria no better (0.53). The TEG parameters generally performed better as predictors of massive hemorrhage based upon the are under their ROC curves (ACT: 0.63, Angle: 0.68 MA: 0.72, LY30: 0.71), skewed toward higher specificity. TH=he composite Global TEG parameter based on Angle, MA and LY30 improved sensitivity markedly and brought the overal area under the curve to 0.74

Conclusion: Admission Rapid TEG is a superior predictor of massive transfusion requirement to existing trauma scoring systems. It is particularly effective when teh TEG tracing is examined as a whole, rather than relying on any one parameter.

 

20.04 Role of Innate Lymphoid Cells in Modulating Trauma-Induced Immune Response in Blunt Trauma Patients

Posted on December 22, 2014

J. Guardado1, O. Abdul-Malak1, Y. Vodovotz1, T. R. Billiar1, R. A. Namas1  1University Of Pittsburg,Surgery,Pittsburgh, PA, USA

Introduction: Traumatic injury elicits broad systemic inflammatory and pathophysiological responses that if go awry, result in immune dysregulation. Clinically, this manifests as remote multiple organ dysfunction (MODS) and increased risk to nosocomial infection (NI), culminating in to a state of persistent critical illness (PCI). Prior studies demonstrated the central role of multiple inflammatory mediators in regulating the post-traumatic inflammatory response, yet, the role of Innate Lymphoid Cells (ILC) and their downstream mediators has not been fully elucidated. Accordingly, we carried out an extensive time course analysis of circulating ILC biomarkers in a cohort of blunt trauma patients to gain insights into the trauma-induced inflammatory response associated with PCI.

Methods: In a cohort of 472 blunt trauma survivors, we performed a retrospective case–control study where 44 trauma patients with a complicated course i.e. with NI were identified and compared to 44 patients with an uncomplicated course i.e. no-NI, selected by matching for demographics, injury severity, and mechanism of injury. Plasma was sampled 3 times within the first 24 h and then from D1 to D7 post-injury, and assayed for IL-22, IL-23, IL-25, and IL-33 biomarkers. MODScore was calculated from the inpatient electronic record. Two-way analysis of variance (ANOVA) and Area under the Curve (AUC) were used to determine statistical significance (p<0.05) and fold change respectively between the two groups. Spearman Correlation Coefficient (CC) was performed to determine the association between MODS and ILC mediators.

Results: Patients with complicated clinical course had a significantly longer ICU length of stay (LOS), hospital LOS, and days on mechanical ventilation when compared to patients with uncomplicated clinical course. Indeed, patients with complicated clinical course exhibited a higher degree of organ dysfunction suggested by a higher Marshall MODScore persistently elevated across D1 through D7. Circulating levels of IL-22, IL-23, IL-25, and IL-33 were significantly elevated upon admission and remained elevated in patients with complicated clinical course. In parallel to these results, AUC analysis revealed a two-fold increase in the aforementioned mediators in patients with complicated clinical course. In addition, MODS correlated positively with levels of IL-22, IL-23, IL-25, and IL-33 in patients with complicated clinical course as compared to patients with uncomplicated clinical course.

Conclusion: These data provide some of the first evidence in humans that cytokines derived from stressed epithelial cells are elevated early and over time in critically ill trauma patients.  We have previously shown that Th2-derived cytokines (IL-4, IL-5, and IL-13) are also elevated in these patients.  Since IL-5 and IL-33 are known to drive Th2 immunity, these processes may be linked and contribute to organ injury in this patient population.

21.02 Thrombelastography is Superior to Trauma Scoring Systems as a Predictor of Massive Hemorrhage

Posted on December 22, 2014

D. Burneikas2, E. E. Moore1,2, M. P. Chapman2,3, H. B. Moore1,2, E. Gonzalez1,2, C. Silliman2,4, A. Banerjee2  1Denver Health Medical Center,Aurora, CO, USA 2University Of Colorado Denver,Aurora, CO, USA 3Georgia Health Sciences University,Augusta, GA, USA 4Children’s Hospital Colorado,Aurora, CO, USA

Introduction: Massive blood transfusion is required in roughly 3% of civilian and 8% of military trauma patients and requires mobilization of enormous hospital and personnel resources to administer. Thus, accurate prediction of the need for massive transfusion in severely injured trauma patients is highly desireable from both a logistical and patient outcome standpoint. To this end, numerous trauma scoring systems have been developed to predict massive transfusion, such as the Trauma-Associated Severe Hemorrhage (TASH) and Assesment of Blood Consumption (ABC) score. These scores are cumbersome to calculate in the chaotic setting of an emergent trauma, therefore we sought to determine if admission assessment of the patient's Rapid thrombelastogram (Rapid TEG) could provide an easier and more reliable predictive parameter for massive hemorrhage and transfusion. 

Methods:  61 consectutive trauma patients of our highest level of activation and deemed likely to require a massive transfusion by the attending surgeon received an admission Rapid TEG. Their ABC and TASH scores were calculated, as well as binary criteria based on the Resusciatation Outcomes Consortium vital sign inclusion criteria and our center's newly implemented MTP entrance trigger criteria. Reciever operating characteristic (ROC) plots were constructed for these scoring systems with respect to massive hemorrhage (defined as 10 or more units of PRBCS in the first 6 hours or death from massive hemorrhage prior to that time) as the binary outcome variable. ROC plots were also constructed for the Rapid TEG parameters: ACT, Alpha Angle, MA and LY30. Lastly, an ROC curve for Global TEG Assessment parameter was constructed based upon an abnormal finding in any of the three most specific TEG parameters for predicting massive hemorrhage (Alpha Angle, MA and LY30) in order to reflect the TEG tracing as a whole. The merits of these various predictive methodologies were compared according the area under their respective ROC curves.

Results: The area under the ROC curves for the scoring systems was generally very poor (ABC 0.50, TASH: 0.58) and the vital sign and MTP criteria no better (0.53). The TEG parameters generally performed better as predictors of massive hemorrhage based upon the are under their ROC curves (ACT: 0.63, Angle: 0.68 MA: 0.72, LY30: 0.71), skewed toward higher specificity. TH=he composite Global TEG parameter based on Angle, MA and LY30 improved sensitivity markedly and brought the overal area under the curve to 0.74

Conclusion: Admission Rapid TEG is a superior predictor of massive transfusion requirement to existing trauma scoring systems. It is particularly effective when teh TEG tracing is examined as a whole, rather than relying on any one parameter.

 

21.05 Prevalence and Impact of Admission Hyperfibrinolysis in Severely Injured Pediatric Trauma Pateints

Posted on December 22, 2014

I. N. Liras1, B. A. Cotton1, J. C. Cardenas1, M. T. Harting1  1University Of Texas Health Science Center At Houston,Houston, TX, USA

Introduction:  Hyperfibrinolysis (HF) on admission is associated with increased mortality in adult trauma patients. Several studies have demonstrated that 9% of severely injured adults present to the emergency department (ED) with HF. The purpose of the current study was to (1) define HF in pediatric patients and a relevant cut-point for therapeutic intervention (if any), (2) identify the prevalence of HF in severely injured pediatric patients, and (3) determine if HF on admission is as lethal a phenomenon as it is in adults. 

Methods:  Following IRB approval, we identified all pediatric trauma admissions (≤17 years old) that met highest-level trauma activation criteria between 01/2010 and 12/2013. Fibrinolysis rates were determined using LY-30 by rapid thrombelastography (rTEG),which represents the percent reduction of the maximal clot amplitude (fibrinolysis) 30 minutes after such amplitude is achieved. HF was defined a priori as initial LY-30 inflection point that translated to a doubling of mortality. Two previous studies in adults demonstrated an inflection point of ≥3%; where mortality doubled from 9 to 20%. We began by identifying a relevant inflection point to define HF and its prevalence, followed by univariate analysis to compare HF and non-HF patients. Finally, a purposeful logistic regression model was developed to evaluate predcitors of mortality in severely injured pediatric patients. 

Results: 819 patients met study criteria. LY-30 values were plotted against mortality. A distinct inflection point was noted at ≥3%, where mortality doubled from 6 to 14%. Of note, mortality continued to increase as the amount of lysis increased, with a 100% mortality demonstrated at an LY-30 ≥30% (compared to 77% in adults).  Using LY-30 ≥3%, patients were stratified into HF (n=197) and non-HF (n=622), with prevalence on admission of 24%. With the exception of HF patients being younger (median 11 vs. 15 years; p<0.001), there were no differences in demographics, scene vitals or injury severity scores between the groups.  On arrival to the ED, HF patients had a lower systolic blood pressure (median 118 vs. 124 mmHg) and lower hemoglobin (median 12.2 vs. 12.7 g/dL); both p<0.001). Controlling for age, arrival vital signs, admission hemoglobin and injury severity (ISS), logistic regression identified admission LY30 ≥3% (OR 6.2, 95% CI 2.47-16.27) as an independent predictor of mortality.

Conclusion: Similar to adults, admission HF appears to reach a critical threshold at LY30 ≥3% in pediatric patients. Admission HF in pediatric patients occurs more frequently than in adults (24 vs. 9%) but is similarly associated with a doubling in mortality (6 to 14%). Admission LY-30 ≥3% carries a 6-fold increased likelihood of mortality in severely injured pediatric patients. HF on admission may serve to rapidly identify those injured children and adolescents likely to benefit from hemostatic resuscitation efforts and to guide anti-fibrinolytic therapy. 

22.02 Heme oxygenase-2 Protects In Hemorrhage/Resuscitation Via Regulation of Hypoxic Responses

Posted on December 22, 2014

J. Luclano1, B. Kautza1, P. Waltz1, B. Zuckerbraun1,2  1University Of Pittsburg,Pittsburgh, PA, USA 2VA Pittsburgh Healthcare System,Pittsburgh, PA, USA

Introduction: Tissue and cellular hypoxia are a component of many disease processes, including shock states and ischemia/reperfusion insults.  Heme oxygenase (HO) enzymes, which are the rate limiting enzymes in the breakdown of heme to free iron, biliverdin, and carbon monoxide (CO), are critical to the maintenance of cellular homeostasis.  HO enzymes have been implicated in the sensing of oxygen levels and the regulation of oxygen consumption. Additionally, mitochondrial responses are critical to changes in oxygen sensing.  Mitochondria act as critical rheostats within a cell to orchestrate cellular responses to various stimuli, including hypoxia. The purpose of these investigations was to test the hypothesis that HO-2 protects againts hemorrhagic shock or hypoxia induced injury.  Furthermore that HO-2 serves as a critical regulator of hypoxic responses in hepatocytes via modulation of mitochondrial signaling.

Methods: C57BL/6 male mice were hemorrahged to a MAP of 20 mmg for 30 minutes and then resuscitated with 2X the maximum shed blood volume with lactated Ringers.  Some mice were pretreated with control siRNA or HO-2 specific siRNA 72 hours prior to  hemorrhage and resuscitation.  Primary hepatocytes were harvested and cultured from C57BL/6 or gp91phox-/- mice.  Cells were exposed to standard culture conditions (5%CO2, and 21% O2) or hypoxia (5%CO2, 1%O2) for 0-12 hours.  In some experiments hepatocytes were pretreated with control siRNA, HO-1 siRNA, or HO-2 siRNA.  Additionally, tin protoporphyrin (SnPP) was utilized as a pharmacological inhibitor of HO.  Western blots or immunohistochemistry for HO-1, HO-2, hypoxic signaling proteins, mitochondrial fusion pathways, and oxidative phosphorylation proteins were performed.  Mitochondrial reactive oxygen species were measured by mitosox fluorescence.  ANOVA was used for statistical analysis and significance wsa assumed a s P<0.05.

Results:  HO-2 siRNA pretreatment effectively limited expression of HO-2 in the liver and exacerbated organ injury ( serum ALT increased 2.5+/-0.9 fold over control siRNA, shocked mice, P<0.05). Additionally, there were significant increases in serum markers of inflammation (IL-6 and TNF-alpha).HO-2 but not HO-1 was expressed in hepatocytes at baseline and was localized within mitochondria.  SnPP or HO-2 siRNA, but not HO-1 siRNA inhibited hypoxia induced mitochondrial ROS.  Furthermore, hypoxia increased HIF1a protein levels, and this was inhibited by HO-2 siRNA or SnPP.  Furthermore, 12 hours of hypoxia exposure led to increased expression of proteins of oxidative phosphorylation and this was inhibited by HO-2 siRNA.

Conclusion:  HO-2 limits organ injury and inflammation in hemorrhagic shock and resuscitation.  This may be through the influence on hypoxia induced mitocohndrial signaling.  Understanding critical adaptive responses in hypoxic type of insults are critical to impriving care and the development of future therapeutics.

 

22.03 Optimal Timing of Tracheostomy for Prolonged Respiratory Failure after Blunt Trauma

Posted on December 22, 2014

J. E. Keenan1, B. C. Gulack1, D. P. Nussbaum1, C. Green1, M. L. Shapiro1, S. N. Vaslef1, J. E. Scarborough1  1Duke University Medical Center,Durham, NC, USA

Introduction: Controversy exists over when tracheostomy should be performed in the critically ill trauma patient with prolonged respiratory failure.  The purpose of this study was to determine the optimal timing of tracheostomy in this population using a large national data source.

Methods: The research data set of the National Trauma Data Bank (years 2008-2011) was used to identify a cohort of adult patients who required tracheostomy within the first 21 days of hospitalization after blunt trauma (with ISS ≥9) and who had been directly admitted to the ICU or operating room from the emergency department.  Patients who may have required tracheostomy for airway stabilization rather than prolonged respiratory failure were excluded, including those who underwent tracheostomy within 4 days from admission, those with head or neck injuries (defined as abbreviated injury scale ≥1), and those who spent less than one day in the ICU.  A restricted cubic spline analysis was performed to determine how timing of tracheostomy was associated with in-hospital mortality. The cohort was stratified based on the results of this analysis.  Unadjusted baseline demographics, characteristics, and outcomes were compared between groups. Multivariable logistic regression analysis was employed to evaluate the independent association of timing of tracheostomy with mortality after adjustment for age, gender, race, payor status, ACS trauma verification level, ISS, and emergency department GCS.

Results: 9,187 patients were included in the study.  Overall in-hospital mortality was 9.9% (n=899).  Based on restricted cubic spline analysis, probability of mortality appeared to be higher in patients who underwent tracheostomy prior to hospital day 11  (Figure). The cohort was therefore stratified into early and delayed tracheostomy groups based on whether the patient underwent tracheostomy before or on/after hospital day 11, respectively.  There were 5,121 (55.7%) patients in the early tracheostomy group, and 4,066 (44.3%) in the delayed tracheostomy group.  Prior to adjustment, the delayed tracheostomy group had a significantly decreased mortality compared to the early tracheostomy group (8.8% vs 10.7%, p=0.004).  Following adjustment with multivariable logistic regression, the delayed tracheostomy group continued to have significantly decreased odds of mortality compared to the early tracheostomy group (AOR: 0.83, 95% CI: 0.71-0.96).

Conclusion: This study of a large national cohort supports that delaying tracheostomy up to hospital day 11 provides survival benefit in patients with prolonged respiratory failure after blunt trauma.  Trauma surgeons and critical care physicians should therefore consider avoiding tracheostomy placement prior to this time point.
 

22.05 Role of Innate Lymphoid Cells in Modulating Trauma-Induced Immune Response in Blunt Trauma Patients

Posted on December 22, 2014

J. Guardado1, O. Abdul-Malak1, Y. Vodovotz1, T. R. Billiar1, R. A. Namas1  1University Of Pittsburg,Surgery,Pittsburgh, PA, USA

Introduction: Traumatic injury elicits broad systemic inflammatory and pathophysiological responses that if go awry, result in immune dysregulation. Clinically, this manifests as remote multiple organ dysfunction (MODS) and increased risk to nosocomial infection (NI), culminating in to a state of persistent critical illness (PCI). Prior studies demonstrated the central role of multiple inflammatory mediators in regulating the post-traumatic inflammatory response, yet, the role of Innate Lymphoid Cells (ILC) and their downstream mediators has not been fully elucidated. Accordingly, we carried out an extensive time course analysis of circulating ILC biomarkers in a cohort of blunt trauma patients to gain insights into the trauma-induced inflammatory response associated with PCI.

Methods: In a cohort of 472 blunt trauma survivors, we performed a retrospective case–control study where 44 trauma patients with a complicated course i.e. with NI were identified and compared to 44 patients with an uncomplicated course i.e. no-NI, selected by matching for demographics, injury severity, and mechanism of injury. Plasma was sampled 3 times within the first 24 h and then from D1 to D7 post-injury, and assayed for IL-22, IL-23, IL-25, and IL-33 biomarkers. MODScore was calculated from the inpatient electronic record. Two-way analysis of variance (ANOVA) and Area under the Curve (AUC) were used to determine statistical significance (p<0.05) and fold change respectively between the two groups. Spearman Correlation Coefficient (CC) was performed to determine the association between MODS and ILC mediators.

Results: Patients with complicated clinical course had a significantly longer ICU length of stay (LOS), hospital LOS, and days on mechanical ventilation when compared to patients with uncomplicated clinical course. Indeed, patients with complicated clinical course exhibited a higher degree of organ dysfunction suggested by a higher Marshall MODScore persistently elevated across D1 through D7. Circulating levels of IL-22, IL-23, IL-25, and IL-33 were significantly elevated upon admission and remained elevated in patients with complicated clinical course. In parallel to these results, AUC analysis revealed a two-fold increase in the aforementioned mediators in patients with complicated clinical course. In addition, MODS correlated positively with levels of IL-22, IL-23, IL-25, and IL-33 in patients with complicated clinical course as compared to patients with uncomplicated clinical course.

Conclusion: These data provide some of the first evidence in humans that cytokines derived from stressed epithelial cells are elevated early and over time in critically ill trauma patients.  We have previously shown that Th2-derived cytokines (IL-4, IL-5, and IL-13) are also elevated in these patients.  Since IL-5 and IL-33 are known to drive Th2 immunity, these processes may be linked and contribute to organ injury in this patient population.

19.03 Heme oxygenase-2 Protects In Hemorrhage/Resuscitation Via Regulation of Hypoxic Responses

Posted on December 22, 2014

J. Luclano1, B. Kautza1, P. Waltz1, B. Zuckerbraun1,2  1University Of Pittsburg,Pittsburgh, PA, USA 2VA Pittsburgh Healthcare System,Pittsburgh, PA, USA

Introduction: Tissue and cellular hypoxia are a component of many disease processes, including shock states and ischemia/reperfusion insults.  Heme oxygenase (HO) enzymes, which are the rate limiting enzymes in the breakdown of heme to free iron, biliverdin, and carbon monoxide (CO), are critical to the maintenance of cellular homeostasis.  HO enzymes have been implicated in the sensing of oxygen levels and the regulation of oxygen consumption. Additionally, mitochondrial responses are critical to changes in oxygen sensing.  Mitochondria act as critical rheostats within a cell to orchestrate cellular responses to various stimuli, including hypoxia. The purpose of these investigations was to test the hypothesis that HO-2 protects againts hemorrhagic shock or hypoxia induced injury.  Furthermore that HO-2 serves as a critical regulator of hypoxic responses in hepatocytes via modulation of mitochondrial signaling.

Methods: C57BL/6 male mice were hemorrahged to a MAP of 20 mmg for 30 minutes and then resuscitated with 2X the maximum shed blood volume with lactated Ringers.  Some mice were pretreated with control siRNA or HO-2 specific siRNA 72 hours prior to  hemorrhage and resuscitation.  Primary hepatocytes were harvested and cultured from C57BL/6 or gp91phox-/- mice.  Cells were exposed to standard culture conditions (5%CO2, and 21% O2) or hypoxia (5%CO2, 1%O2) for 0-12 hours.  In some experiments hepatocytes were pretreated with control siRNA, HO-1 siRNA, or HO-2 siRNA.  Additionally, tin protoporphyrin (SnPP) was utilized as a pharmacological inhibitor of HO.  Western blots or immunohistochemistry for HO-1, HO-2, hypoxic signaling proteins, mitochondrial fusion pathways, and oxidative phosphorylation proteins were performed.  Mitochondrial reactive oxygen species were measured by mitosox fluorescence.  ANOVA was used for statistical analysis and significance wsa assumed a s P<0.05.

Results:  HO-2 siRNA pretreatment effectively limited expression of HO-2 in the liver and exacerbated organ injury ( serum ALT increased 2.5+/-0.9 fold over control siRNA, shocked mice, P<0.05). Additionally, there were significant increases in serum markers of inflammation (IL-6 and TNF-alpha).HO-2 but not HO-1 was expressed in hepatocytes at baseline and was localized within mitochondria.  SnPP or HO-2 siRNA, but not HO-1 siRNA inhibited hypoxia induced mitochondrial ROS.  Furthermore, hypoxia increased HIF1a protein levels, and this was inhibited by HO-2 siRNA or SnPP.  Furthermore, 12 hours of hypoxia exposure led to increased expression of proteins of oxidative phosphorylation and this was inhibited by HO-2 siRNA.

Conclusion:  HO-2 limits organ injury and inflammation in hemorrhagic shock and resuscitation.  This may be through the influence on hypoxia induced mitocohndrial signaling.  Understanding critical adaptive responses in hypoxic type of insults are critical to impriving care and the development of future therapeutics.

 

19.07 Acid Sphingomyelinase Inhibition Decreases Lung Injury after Transfusion with Stored Blood

Posted on December 22, 2014

R. S. Hoehn1, P. L. Jernigan1, E. F. Midura1, J. M. Sutton1, C. C. Caldwell1, M. J. Edwards1, E. Gulbins1,2, T. A. Pritts1  1University Of Cincinnati,Surgery,Cincinnati, OH, USA 2University Of Duisburn-Essen,Molecular Biology,Essen, ESSEN, Germany

Introduction:  Transfusion of human packed red blood cell units (pRBCs) is ideal for resuscitation after hemorrhage. However, studies have shown that use of aged pRBCs are associated with increased morbidity and mortality compared to fresh units. Our laboratory and others have demonstrated that pRBC storage results in accumulation of microparticles that cause increased lung inflammation after transfusion. Ceramide, a sphingolipid formed by the enzyme acid sphingomyelinase (Asm), is present in cell membranes and mediates a variety of cell signaling and membrane changes in red blood cells, but its role in microparticle formation is unknown. We hypothesized that Asm inhibition would lead to decreased ceramide accumulation and microparticle formation in pRBCs, with a resultant decrease in lung injury after hemorrhage and resuscitation.

Methods:  Human and murine pRBCs were obtained and treated with increasing concentrations of Amitriptyline (AT), a specific Asm inhibitor, or vehicle, then stored under standard blood banking conditions. At intervals, microparticles were isolated from pRBC units and quantified with Nanoparticle Tracking Analysis. Asm activity and ceramide concentration were measured in stored erythrocytes and microparticles. Mice underwent hemorrhage and resuscitation with equal numbers of microparticles from AT- and vehicle-treated pRBC units. Lungs were collected from shocked mice and assessed for inflammatory cytokines and histology.

Results: During storage, pRBC units demonstrated significantly increased microparticle formation, ceramide accumulation, and Asm activity. Human and murine pRBCs treated with AT formed fewer microparticles in a dose-dependent manner (Figure 1A). AT-treated pRBCs and microparticles contained less ceramide and Asm activity. After hemorrhage, mice resuscitated with microparticles isolated from vehicle-treated pRBCs had significantly elevated lung levels of pro-inflammatory cytokines including macrophage-derived chemokine (Figure 1B), IL-1b, IL-6, KC, MCP-1, MIP-1a, and MIP-2 as well as increased lung damage as determined by histology. Resuscitation with equal numbers of microparticles from AT-treated pRBCs resulted in significantly decreased lung injury.

Conclusion: Amitriptyline treatment of pRBC units leads to decreased Asm activity, ceramide formation, and microparticle accumulation. Asm inhibition caused alterations in the microparticles that led to decreased acute lung injury following hemorrhage and resuscitation. Asm inhibition represents a novel opportunity to mitigate harmful effects of resuscitation with stored pRBCs.

 

18.19 Prehospital Trauma Care Education for First Responders in Western Rajasthan

Posted on December 22, 2014

A. Aekka2, M. V. Hollis2, E. M. Boudiab2, G. P. Laput2, H. Purohit3, A. K. Vyas2,4, D. Vyas1,2  1Michigan State University,Department Of Surgery,Lansing, MI, USA 2Michigan State University,College Of Human Medicine,Lansing, MI, USA 3Arogyaa.com,Meerut, UP, India 4Michigan State University,Department Of Pediatrics,Lansing, MI, USA

Introduction:

The burden of trauma and injury is particularly devastating for developing nations such as India. The crux of the problem lies in the astonishing lack of prehospital trauma services: 80% of trauma victims in India cannot access medical care within the first hour. Existing health education initiatives fail to engage first responders and neglect the local context. 

Methods:
A 2-day hands-on prehospital trauma management training program with video lectures was developed for first responders in the local language. The course consists of 10 interactive sessions dealing with essential prehospital trauma care concepts, such as airway establishment, hemorrhage control, CPR, fracture stabilization, triage, and communication. Extensive self-learning videos, which help to overcome the language barrier, and high-fidelity simulation, which presents the most realistic training experience, provide a level of engagement that traditional didactic methods cannot offer. Video-debriefing serves as a valuable evaluation method. First responders are further introduced to advanced tools, such as the King LT airway and pulse oximeter, but are instructed in improvised management as resources are limited on the field. A comprehensive, but concise manual and specialized tool kit were also developed for trainees.
 
48 participants from Jodhpur, Rajasthan, including police officers, firemen, ambulance and taxi drivers, EMTs, hospital staff, and nursing staff and students, attended the pilot course. 18 instructors were recruited from Jodhpur and included medical students/residents and faculty, private practice physicians, and police officials. These individuals were trained in a 4-hour session prior to the program regarding the course content, materials, expectations, methods of engagement, and principles, such as collaborative learning, positive reinforcement, and the use of native, lay-person language.
 

Results:
Pre- and post-training surveys were used to evaluate participants' competence in managing 10 prehospital trauma matters. Statistically significant increases in competence were demonstrated for all topics: Airway (35.0%), Hemorrhage (36.1%), Fractures (32.0%), Cervical Spine Injury (45.4%), Chest Injury (41.3%), IV Line Placement (29.9%), Extrication (18.6%), Scene Assessment (35.1%), Triage (26.5%), and Communication (25.4%). The greatest increases were observed in cervical spine and chest injury management. The lowest, but still significant, increases were observed in extrication and communication. A six-month post-training survey will be conducted.

Conclusion:
First responder training in the native language with simulation and video-debriefing improves understanding and skills in all essential aspects of prehospital care, however, results suggest that discussion of extrication and communication should be strengthened. The goal is to develop a program that engages and prepares first responders in the procedural, cognitive, and affective aspects of prehospital trauma management.

18.20 Novel Simulation Course for Application of Resuscitative Endovascular Balloon Occlusion of Aorta

Posted on December 22, 2014

R. A. Lawless1, J. D. Love1  1University Of Texas Health Science Center At Houston,Acute Care Surgery,Houston, TX, USA

Introduction:
Noncompressible truncal hemorrhage (NCTH) remains a major cause of death from traumatic injuries both in military and civilian populations.  Recent interest in resuscitative endovascular balloon occlusion of the aorta (REBOA) has shown promise as an alternative to resuscitative thoracotomy and adjunct to preperitoneal packing for NCTH.  General surgery residents and fellows are exposed to this technique in the elective and emergent setting during abdominal aortic aneurysm repair.  However, this skill is not always maintained in surgeons not planning on completing a vascular surgery fellowship.  The recent interest in REBOA has brought a need for training in this technique for both new trainees and current trauma attendings.

Methods:
Between the University of Texas Health Science Center and Texas Medical Center the Advanced Surgical Skills for Exposure in Trauma (ASSET) is held four times per year.  The curriculum is followed as determined by the ACS Committee on Trauma.  Following course completion, a didactic session, anatomic demonstration, and simulation session for the REBOA was introduced.

Results:
Participants included PGY-3, PGY-4, PGY-5, PGY-6, general surgery faculty, and trauma/critical care faculty.  From June 2012 to March 2014, 64 participants completed the simulation course.  Following the course a number of participants have utilized the technique learned from the course in the care of their trauma patients.  

Conclusion:
The REBOA technology can be taught to trainees and surgeons in practice and immediately applied in the trauma setting.  Course participants are confident in this technique of minimally invasive control of NCTH.  Future and ongoing plans for the course include a pre-test, post-test, self-assessment, and course survey.

19.02 Inhibition of Ubiqutin-Activating Enzyme Protects Organ Injury from Intestinal Ischemia-Reperfusion

Posted on December 22, 2014

W. Yang1, S. Matsuo2, A. J. Chaung1, P. Wang1  1Hofstra North Shore-LIJ School Of Medicine,Surgery,Mnahasset, NY, USA 2Tokyo Women’s Medical University,Surgery,Tokyo, , Japan

Introduction:  Intestinal ischemia-reperfusion (I/R) occurs in various clinical settings, such as transplantation, acute mesenteric arterial occlusion, trauma and shock. I/R injury causes severe systemic inflammation, leading to multiple organ dysfunction associated with high rates of morbidity and mortality. Ubiquitin proteasome pathway has been indicated in the regulation of inflammation, particularly through NF-κB signaling pathway. PYR-41 is a small molecule compound that selectively inhibits ubiquitin-activating enzyme E1. We hypothesized that administration of PYR-41 attenuated organ injury after intestinal I/R.

Methods:  Male C57BL/6 mice (20-25 g) were subjected to intestinal ischemia by clamping the superior mesenteric artery for 45 min, followed by reperfusion. At the beginning of reperfusion, PYR-41 (5 mg/kg BW) or 20% DMSO (vehicle) in normal saline was administered intravenously (n=5/group). After 4 h, blood and tissues were collected for various measurements. Apoptotic cells in tissue sections were detected by TUNEL assay. Cytokines were measured by ELISA. Ubiquitination and protein levels were determined by Western blotting. Gene expression was assessed by qPCR.

Results:PYR-41 significantly reduced LDH, AST and IL-6 serum levels from 752.8 to 155.3 IU/L, 76.7 to 47.0 IU/L and 10.4 to 5.1 ng/ml, respectively, compared to the vehicle group (P < 0.05). The integrity of microscopic structures of the small intestine and lungs was much more preserved in the PYR-41-treated group than in the vehicle group (Figure). PYR-41 decreased the number of TUNEL-positive cells in the small intestine and lungs from 144 to 32 and 120 to 38 cells/field, respectively, which were associated with a reduction of cleaved caspase-3 levels in both organs. The IL-6 and IL-1β levels were decreased from 166.8 to 64.8 and 65.8 to 37.7 pg/mg protein in the intestine as well as from 53.2 to 38.3 and 132.6 to 70.7 pg/mg protein in the lungs, respectively, with PYR-41 treatment. Myeloperoxidase activity in the intestine and lungs is reduced by 69% and 38%, respectively, with PYR-41 treatment. PYR-41 also inhibited the expression of KC and MIP-2 mRNA in the intestine as well as lungs. In addition, PYR-41 inhibited the degradation of IκB in the intestine and the ubiquitination in the lungs after intestinal I/R.      

Conclusion: Treatment with PYR-41 effectively attenuates intestinal and pulmonary injuries through inhibiting NF-κB activation to reduce local and systemic inflammation after intestinal I/R. Thus, ubiquitination may be a potential therapeutic target for treating patients suffering from intestinal I/R.

 

17.01 Mortality and Discharge Outcomes For Higher vs. Lower Level Trauma Centers in Isolated Hip Fracture Patients

Posted on December 22, 2014

H. Nelson-Williams1, J. Canner1, E. Schneider1, D. T. Efron1, E. R. Haut1, B. Shafiq1, A. H. Haider1, C. G. Velopulos1  1Johns Hopkins University School Of Medicine,Surgery,Baltimore, MD, USA

Introduction:
Younger, multi-trauma patients have improved survival when treated at a trauma center (TC). Many regions are now proposing that patients over age 65 be triaged to a higher level TC (HLTC) vs. lower level TC (LLTC), even for isolated injury, despite the absence of an established benefit in this elderly cohort. We therefore sought to determine if isolated hip fracture patients have improved survival outcomes based on trauma center level.

Methods:
A retrospective cohort of 1.07 million patients in The Nationwide Emergency Department Sample (NEDS) from 2006 to 2010 was used to identify 239,288 isolated hip fracture patients aged 65 to 105 years. Patients were stratified by AIS score. Multivariable logistic regression was performed controlling for age, sex, Charlson index, payor, zip code, teaching status, location, and region. The main outcome measures were in-hospital mortality and discharge disposition among patients admitted to a HLTC (Level I or II) vs. a LLTC center (Level III or non-designated TC).

Results:
Nearly all patients had an extremity AIS 3 (99.9%). Unadjusted logistic regression analyses revealed 8% higher odds of mortality (OR 1.08; 95% CI 1.00-1.16) and 10% lower odds of being discharged home (OR 0.90; 95% CI 0.80-1.00) among patients admitted to a HLTC versus LLTC. After controlling for patient and hospital-level factors, neither the odds of mortality (OR 1.06; 95% CI 0.97-1.15) nor the odds of discharge to home (OR 0.98; 95% CI 0.85-1.12) differed significantly between patients treated at a HLTC vs. LLTC. There were differences across payer (Table 1) and region for discharge home, with patients in the South and West more likely to be discharged home than to rehab.
 

Conclusion:
Among patients with isolated hip fractures, those admitted to a HLTC do not differ in mortality or discharge disposition from similar patients admitted to a LLTC. These findings may have important implications for trauma systems and triage protocols.
 

17.02 Trauma System Regionalization across State Borders

Posted on December 22, 2014

J. J. Sumislawski1, S. A. Savage1, B. L. Zarzaur2  1University Of Tennessee Health Science Center,Memphis, TN, USA 2Indiana University School Of Medicine,Indianapolis, IN, USA

Introduction: Organization of trauma centers into a state trauma system is associated with reduced mortality. Development of a trauma system could affect a neighboring state’s trauma center. In 2010, an inclusive trauma system was implemented that allowed centers in bordering states to participate. This study was designed to examine the effect of the development of this new trauma system on a participating out-of-state Level 1 trauma center.

Methods: Patients referred to a participating out-of-state trauma center were included. Using a difference-in-differences approach, residents of the state with the new trauma system (TSystem patients) were compared with residents of the state with the trauma center (TCenter patients) PRE (2008-2009) and POST (2011-2012) implementation of the trauma system.

Results: TCenter patients decreased 3% PRE versus POST while TSystem patients increased 39% (Table 1). Injury severity did not change for TCenter patients but decreased for TSystem patients PRE (mean Injury Severity Score 15) versus POST (12, p<0.05). Transfers from referring hospitals increased from both states. For TSystem patients, air arrivals decreased and payer status did not change. Compared with TCenter patients, odds of mortality for TSystem patients decreased PRE (OR 0.97; 95% CI 0.72, 1.31) versus POST (OR 0.73; 95% CI 0.53, 0.99). When only those with ISS >10 were analyzed, mortality did not change PRE (OR 0.85; 95% CI 0.60, 1.20) versus POST (OR 0.96; 95% CI 0.67, 1.37). Secondary overtriage increased PRE (OR 0.67; 95% CI 0.54, 0.83) versus POST (OR 1.53; 95% CI 1.32, 1.78) for TSystem patients.

Conclusion: Development of a state trauma system resulted in an increase in less severely injured patients referred to an out-of-state trauma center without change in payer status. For patients of higher injury severity, there was no change in odds of mortality PRE versus POST for either state. Trauma-system implementation promoted overtriage of in-state patients to the out-of-state trauma center. Despite increases in volume and overtriage, allowing participation of a neighboring state’s trauma center did not result in increased mortality for either state’s residents.

 

17.03 Break a Leg Not the Bank: Should We Treat Simple Fractures in Trauma Centers?

Posted on December 22, 2014

F. Gani1, N. Nagarajan1, H. Alshaikh1, C. K. Zogg1, H. Alturki1, S. Selvarajah1, A. Najafian1, L. Kodadeck1, C. G. Velopulos2, D. T. Efron2, E. B. Schneider1, A. H. Haider1  1Johns Hopkins University School Of Medicine,Center For Surgical Trials And Outcomes Research, Department Of Surgery,Baltimore, MD, USA 2Johns Hopkins University School Of Medicine,Department Of Surgery,Baltimore, MD, USA

Introduction:  Healthcare policy efforts are increasingly geared toward providing higher quality care at lower costs. For fractures alone, healthcare spending in the United States is estimated to be >$20 billion per year. Previous data for severely injured patients suggest an improvement in survival at trauma centers. Little is known about possible differences in patient charges for the management of non-life threatening conditions at trauma centers vs. non-trauma center hospitals. Using uncomplicated, closed tibial fractures as an index condition, this study examined possible differences in patient charges at level 1 trauma centers (TC) compared with non-trauma centers (NTC).

Methods:  Data from the 2006-2011 HCUP Nationwide Emergency Department Sample (NEDS) were queried and patients with a primary diagnosis of closed tibial fracture who underwent routine same-day discharge from the emergency department (ED) were identified using ICD-9-CM diagnosis codes. Patients with an Abbreviated Injury Scale (AIS) extremity score of ≤2 were included in the study cohort. Patients with other major concomitant injuries listed in diagnosis positions 2-15 were excluded as were individuals who had a calculated  AIS >0 in any region except “extremity.” Patient demographics, injury and hospital characteristics were compared between TC and NTC using χ² and t-tests. Wilcoxon rank-sum tests examined TC vs. NTC difference in median patient charges. A generalized linear model with a gamma distribution and robust error variances (adjusted for age, sex, insurance status, Charlson comorbidity index, income quartile, mechanism of injury and hospital region) examined differences in mean total charges between patients treated at TC and NTC.

Results: A total of 15,773 patients met inclusion criteria. 1,845 patients were treated at TC and 13,361 patients at NTC. Patients at TC were younger compared to those at NTC, median age 44 (IQR = 32-56) and 48 years (IQR = 38-60) respectively. Proportionally fewer female patients were treated at TC vs. NTC (44.77% vs. 51.21%, p<0.001). Median total charges were higher at TC vs. NTC [$2,278, (IQR $1,259-$4074) vs. $1,351, (IQR $848-$2,313), p<0.001]. Adjusted charges for management in the ED were 94% higher at TC vs. NTC [$3,781 (95%CI $3,548-$4,013) vs. $1,951 (95% CI $1,902-$2,000) p<0.001].

Conclusion: Patients undergoing routine same-day discharge after ED treatment of an uncomplicated tibial fracture at TC incur substantially higher charges than otherwise similar patients treated at NTC. Better understanding the factors underlying the differences in charges observed between TC vs. NTC facilities may enable substantial savings to the healthcare system.

 

17.04 The Relationship Between Blood Alcohol Level and Injury Severity: Is the Floppy Patient Myth True?

Posted on December 22, 2014

C. Valdez1, C. Renne1, M. Radomski1, R. Amdur1, J. Dunne1, B. Sarani1  1George Washington University School Of Medicine And Health Sciences,General Surgery,Washington, DC, USA

Introduction:
The impact of inebriation on severity of injury is unclear.  Conventional teaching suggests increasing blood alcohol level (BAL) may be associated with fewer injuries because the patient is limp due to intoxication at the time of injury. The few studies to date on this topic are limited to a particular mechanism of injury (MOI), injury pattern, or BAL. Therefore we sought to determine the impact of BAL on injury pattern and severity across all MOI. We hypothesize that there is no relationship between BAL and injury severity when controlling for MOI. 

Methods:
Following IRB approval, a retrospective study was performed at an adult trauma center from January 1, 2011 to December 31, 2012. All MOI were included. Injury severity was assessed using the injury severity score (ISS). Chi square and ANOVA were used to examine the relationship between BAC, injury pattern, and ISS within each MOI. Multivariate regression model (MVR) examined the BAC-ISS association adjusting for MOI, gender, and age. 

Results:
Of 1397 patients, the mean age was 44±19, mean ISS was 7.5±6.8, mean BAL was 92±130 mg/dL and 70% were male. Overall mortality rate was 1.3%. Rib fracture (p=0.002) and hemo/pneumothorax (p=0.0009) were negatively associated with BAL, while concussion and laceration had a positive association with BAL (p<0.0001). An increasing BAL had a negative correlation with ISS following fall from standing (p<0.001).  Across all MOI combinde, there was no significant association between BAL and ISS. 

Conclusion:
Inebriated patients have a decreased risk of rib fractures and hemo/pneumothoax, and an increased risk of concussion or laceration.  Increased BAL is associated with a lower ISS in the specific MOI of fall from standing. However, across all MOI, there was no significant association between BAL and ISS when controlling for MOI.  Inebriated patients should be triaged and approached with the same clinical index of suspicion for injury as sober patients. 

17.05 Trends in the treatment of pelvic fractures 2008-2010: Where do we stand?

Posted on December 22, 2014

C. Chu2, L. Tennakoon1, D. Spain1, K. Staudenmayer1  1Stanford University,Surgery,Palo Alto, CA, USA 2University Of South Carolina School Of Medicine,Columbia, SC, USA

Introduction: Bleeding from pelvic fractures can be life-threatening. Treatment for bleeding pelvic fractures involves noninvasive means (pelvic binders) and invasive procedures such as angioembolization (AE) and external fixation (EXFIX).  It is not known how frequently these modalities are used in U.S. trauma centers or whether there have been trends over time.  We hypothesized that there would be an increase in the use of AE and a decrease in the use of EXFIX over time. We also sought to determine if the procedures were associated with a reduction in mortality.

Methods: We used the National Trauma Databank (NTDB) from 2008-2010.   Patients were included in the study if they had the International Classification of Diseases, 9th edition and Clinical Modification (ICD-9-CM) codes for pelvic fractures.  Patients were excluded if they were <18 years, had an isolated acetabular fracture, were not admitted to the hospital, or had an ISS<15.  Only centers that had demonstrated an ability to perform AE or EXFIX were included in the analysis.  The primary outcomes were whether the patient had an AE or EXFIX within the first 24 hours after admission. The secondary outcome was mortality. Univariate analyses and multi-level logistic regression (to control for center effects) were used.

Results: A total of 22,568 met inclusion and exclusion criteria.  Patients were predominantly male (59.6%), white (70.3%), and between the ages of 18 and 44 (50.7%).   Overall, AE and EXFIX were performed in 746 (3.3%) and 663 (2.9%) of patients, respectively.  Patients who received AE and EXFIX were different across all measures in unadjusted analyses, but after adjusting for known confounders, only age, injury severity, physiologic instability, and diagnosis of shock were associated with receiving a procedure.    Over the study period, there was an increase in the use of AE (2.5% in 2007 to 3.7% in 2010, p<0.001), which remained significant in adjusted analysis (OR per year 1.15, p=0.008).  There was no significant trend for EXFIX.  AE and EXFIX were associated with a higher mortality in unadjusted analyses compared to those who did not receive a procedure (11.0% for no procedure vs. 20.5% and 13.4% for AE and EXFIX, respectively; p<0.001).  In adjusted analyses, AE remained associated with higher mortality (OR 1.63, p<0.001), whereas EXFIX was associated with a slightly lower risk (OR 0.95, p<0.01).

Conclusion: The use of AE in severely injured pelvic fracture patients is increasing.  However, this procedure is associated with a higher mortality.  It is possible that AE is used more often in patients at high risk of death, but that its use does not reduce this risk.  We should carefully examine the use of this expensive resource in future studies.

 

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