50.08 Under Fire: Gun Violence is not just an Urban Problem

Posted on December 22, 2014

C. Morrison1, K. Bupp1, B. Gross1, K. Rittenhouse1, F. Rogers1  1Lancaster General Hospital,Trauma,Lancaster, PA, USA

Introduction: Gun violence continues to be a source of trauma patient morbidity and mortality annually in U.S. communities. Recent research suggests increasing gunshot violence severity in urban centers. We sought to characterize gun violence in the combined suburban and rural county of Lancaster, PA, to compare it to gun violence results obtained in urban areas.

Methods:  In a Pennsylvania-verified, level II trauma center, treated gunshot wounds (GSW) from January 2000 to December 2013 were queried from the trauma registry. BB/pellet GSWs were excluded. Data collected included mortality, ISS, and number of GSW per patient. Cost data was obtained for patients from 2004-2013, and costs were calculated using cost-charge modifiers. A binary logistic regression was performed to assess mortality over time. Linear trend tests assessed the change in percent of patients with 3 or more GSWs, with ISS≥15 and ISS≥25 over the 14-year study period. Significance was defined as p<0.05.

Results: A total of 478 patients met inclusion criteria. Of these patients, 83.3% sustained interpersonally-inflicted GSWs, while the remaining 16.7% sustained self-inflicted GSWs. The population was 62% white, 35% black, and 3% other.  Risk-adjusted mortality (for age, ISS) showed no significant change in mortality over time (p=0.999). Linear trend tests revealed no significant changes in percent of patients with 3 or more GSWs (p=0.693), with ISS≥15 (p=0.546), or with ISS≥25 (p=0.342) over time. No significant change in cost per case was found (p=0.380), however percent reimbursement significantly increased (p=0.009).

Conclusion: Even the fairly suburban and rural communities of Lancaster County, PA are not sheltered from the problem of gun violence, although the rate seems to be stable in a non-urban environment. Despite advances in pre-hospital and hospital care, including damage control techniques, the mortality from GSW has not changed. Future efforts to improve the outcome for GSW should focus more on preventative efforts.
 

50.09 Percutaneous versus Surgical Tracheostomy: a meta-analysis.

Posted on December 22, 2014

C. J. Lee1, R. S. Chamberlain1,2,3  1Saint Barnabas Medical Center,Surgery,Livingston, NJ, USA 2New Jersey Medical School,Newark, NJ, USA 3Saint George’s University,Grenada, Grenada, Grenada

Introduction:  Percutaneous tracheostomy (PT) was first described by Toye and Weinstein in 1969, and has gained wide acceptance.  Despite being the procedure of choice in many ICUs, ongoing controversy over complication rates has led many surgeons to prefer standard open tracheostomy (ST) versus PT.   This meta-analysis assesses all randomized controlled trials (RCTs) comparing PT to ST evaluating operative time and postoperative outcomes to develop evidence based recommendations on tracheostomy method. 

Methods:  A comprehensive literature search of PubMed, the Cochrane Central Register of Controlled Trials, and Medline was performed. 21 prospective, RCTs were identified comparing PT with ST in adult, intensive care unit patients requiring tracheostomy (1991-2014). Data were extracted on study design, study size, rate of tracheostomy site infection, rate of intraoperative and postoperative hemorrhage, rate of pneumothorax, rate of subcutaneous emphysema, and recorded operative time.

Results: 21 trials involving 2,074 subjects were included in the meta-analysis. Among these 2,074 adult ICU patients, 996 involved PT, and 1,078 were ST. PT techniques included Cook Blue Rhino, Ciaglia and Griggs’ techniques. PT was associated with a 65% decrease in the likelihood of wound infection (risk ratio (RR) 0.35; 95% CI, 0.22 to 0.54, p<0.001) and significantly shorter operative time (Standard difference in means -1.67; 95% CI, -2.25 to -0.99, p<0.001) compared to ST. No significant differences in intraoperative hemorrhage (p=0.675), postoperative hemorrhage (p=0.287), pneumothorax (p=0.528) or subcutaneous emphysema rates were observed (p=0.484). 

Conclusion: PT is associated with a significant decrease (65%) in the incidence of wound infection when compared to ST, and is comparable regarding other major operative complications such as hemorrhage, pneumothorax, and subcutaneous emphysema. PT can be performed in a significantly shorter amount of time compared to ST. In the critically ill patient in an intensive care setting, PT can be recommended as the procedure of choice and a safe alternative when an elective tracheostomy is required.

 

50.10 Paravertebral Blocks Significantly Reduce the Risk of Death in Patients with Mulitple Rib Fractures

Posted on December 22, 2014

K. Basiouny1, N. Gamsky1, B. Sarani1, P. Dangerfield1, R. L. Amdur1, M. Rose2, J. Dunne1  2George Washington University School Of Medicine And Health Sciences,Department Of Anesthesia,Washington, DC, USA 1George Washington University School Of Medicine And Health Sciences,Division Of Trauma, Department Of Surgery,Washington, DC, USA

Introduction

Multiple rib fractures are associated with significant morbidity and mortality. Attempting to find a way to mitigate theses complications, we began placing paravertebral blocks (PVB) in such patients.  The goal of this study is to assess the efficacy of PVB in patients with multiple rib fractures compared to the national trauma data bank (NTDB).  We hypothesize that PVB significantly improve survivability.

Methods

The 2008 NTDB was to develop expected death rates based on patient characteristics and compared against a consecutive cohort of patients in a single level I trauma center from 2011 to 2014. Patients 18 years or older with ≥ 3 rib fractures or a sternal fracture and hospital length of stay > 3 days were included. Variables abstracted include: demographics; rib fracture variables (number of ribs fractured, sternum fracture, flail-chest); injury type (blunt, penetrating, burn); Glasgow coma score (GCS), and injury severity score (ISS).  A logistic regression model using gender, age, GCS, ISS, and number of ribs fractured was developed from the NTDB and then used in our sample to predict death. The PVB x risk interaction was added to this model to determine if the association between risk and outcome varies significantly based on whether or not PVB was present. Probability of death was grouped into 6 risk strata: 10th, 25th, 50th, 75th, and 90th percentile and examined with chi-square grouped by the presence or absence of PVB.

Results [BS1] 

The NTDB cohort consists of 35058 patients. The lowest 10% had a death rate of 0.3%, while the highest 10% had a death rate of 32.6. The association between the risk category and death was strong (phi=.40, p<.0001).  There were 318 GW patients with 3 or more rib fractures with 81 that received PVB, all trauma patients cared for from 2011 to 2014. We collected age, ISS, GCS, gender, and total fracture numbers.  There appeared to be difference between the GW cohort and the NTDB.  Patients with the highest two risk stratified death rates who received a PVB had a much lower than the expected death rate. In the model using Risk score and PVB as predictors, the prediction model for death was very accurate (c=.95) with sensitivity and specificity of .89 & .90 respectively.   The OR for Risk was 7.86 [3.80-16.26], p<.0001. This indicates that for every 1-step increase in the risk score (from 1 to 6), the odds of death increases almost 8 times. The OR for PVB was 0.14 [0.02-1.22], p=.075.  The length of stay in the hospital was significantly higher in the highest risk stratified group who received PVBs with an R2 of .41.    

Conclusion

Patients in the highest risk stratified groups with ≥ 3 rib or sternal fractures have improved survival with use of paravertebral blocks.

50.01 Transport Time as a Factor in the Survival Benefit of Trauma Patients Transported by Helicopter

Posted on December 22, 2014

J. B. Brown1, M. L. Gestring2, M. R. Rosengart1, A. B. Peitzman1, T. R. Billiar1, J. L. Sperry1  1University Of Pittsburgh,Department Of Surgery,Pittsburgh, PA, USA 2University Of Rochester,Department Of Surgery,Rochester, NY, USA

Introduction:
Helicopter transport (HT) following traumatic injury has been shown to improve survival; however the contibution of factors such as speed and crew resources are not clear. The study objective was to examine the impact of HT vs ground transport (GT) on survival across similar prehospital transport times (PHTT).

Methods:
Subjects >15 years undergoing HT or GT from the scene of injury in the National Trauma Databank (2007-2012) were included. Subjects were excluded if dead on arrival or missing PHTT. PHTT was stratified by 5min increments between 0 and 60mins. To account for differences between HT and GT groups, propensity score matching was used to estimate the probability of HT. Variables in the propensity-score included age, sex, prehospital vital signs, prehospital response and scene time, injury severity score, and mechanism of injury. 1:1 nearest neighbor matching was used to match HT and GT subjects on the probability of undergoing HT. Standardized differences were used to assess balance after matching. Conditional logistic regression was used to determine the association of HT vs GT with in-hospital survival across PHTT strata, controlling for ICU admission, emergent surgery, mechanical ventilation, and insurance status. False discovery rate correction was used for multiple comparisons. Transport distance was estimated from PHTT using national average HT and GT transport speeds.

Results: 
156,010 pairs were matched, giving 312,020 subjects for analysis. The propensity score model had good discrimination (AUC=0.91).  After matching, no variable in the propensity score had a standardized difference >0.2 with a 77% reduction in overall bias. HT subjects required ICU admission, emergent surgery, and mechanical ventilation more often than GT subjects (p<0.01). HT vs GT median prehospital response time (19min vs 19min) and scene time (14min vs 15min) were similar.  Median PHTT in the HT group was 21min (IQR 16, 30) compared to 23min (IQR 15, 36) in the GT group (p<0.01). HT vs GT was independently associated with an increased odds of survival in a time window between 6 and 25mins (Fig). This corresponds to an estimated transport distance between 14.3 and 59.4mi for HT, and 3.3 and 13.8mi for GT. The survival benefit of HT peaked at a PHTT of 11-15min (OR 2.02; 95%CI 1.70-2.41, p<0.01).

Conclusion:
The survival benefit for HT in trauma at the population level is concentrated in a PHTT window between 6 and 25mins. These results highlight the importance of logistical considerations and the potential influence of crew resources on outcome for HT in trauma, with implications for trauma system design and planning. Further study of the interplay between transport time, distance, and survival for HT in trauma is warranted.

50.02 Does Decade of Life Matter: An Age Related Analysis of SICU Patients

Posted on December 22, 2014

N. Melo1, J. Chan1, J. Mirocha1, M. Bloom1, E. Ley1, R. Chung1, D. Margulies1  1Cedars-Sinai Medical Center,Los Angeles, CA, USA

Introduction: With the increasing aging population in the Intensive Care Unit (ICU), we analyzed patients admitted to our Surgical ICU to determine if age had an effect on mortality and complications.

Methods: A retrospective chart review was conducted between February 2011 and January 2014 on all patients admitted to the Surgical ICU at our institution.   Patient demographics and complications were analyzed using decade of life (< 50, 50-60, 60-70, 70-80, ≥ 80) to determine whether this influenced outcomes and rate of complications.  ANOVA and Chi-Squared tests were used as appropriate for analysis.

Results:  2,272 patients were included in the study.  Patients were 55.3% male, average age was 59.7 years, and average APACHE score of 26.68.  We found that mortality increases with increasing age (p<0.05).  There was no difference in ICU length of stay (LOS), or Ventilator Days.  With increasing age, there were increases in rates of Deep Vein Thrombosis (DVT), Sepsis, Urinary Tract Infection (UTI), Arrhythmias, Shock, and Pulmonary Embolism (PE) (p< 0.05).    We saw an increase in renal failure for ages 50-70.   There were no differences in GI bleeds.   Rates of SIRS declined with increasing age.

Conclusion:  Although ICU mortality is known to increase with age, we demonstrate that patients as young as 50 start to have an increase risk of complications.    Interestingly, LOS and Ventilator Days were not affected by age.   SIRS was decrease as patients aged, which may be related to the inability to mount an early physiologic response.   This study will help to increase vigilance in the ICU and help with utilization of resources.

50.03 Trajectory Subtypes After Injury: Implications In The Era Of Patient Centered Outcomes

Posted on December 22, 2014

B. L. Zarzaur1, T. M. Bell1, B. L. Zarzaur1  1Indiana University School Of Medicine,Surgery,Indianapolis, IN, USA

Introduction:  The recent focus on patient centered outcomes highlights the need to better describe recovery trajectories in terms of patient quality of life for surgical disease.  Most clinicians and patients expect an initial large decrease in physical and mental functioning after injury followed by a gradual increase in both during recovery. However there is little data regarding the existence of subtypes of recovery trajectories following non-neurologic injury. The purpose of this study was to characterize the types of recovery trajectories that exist after non-neurologic moderate to severe injury.    

Methods:  Adults admitted towith an injury severity score > 10 but without traumatic brain injury or spinal cord injury were eligible. A baseline quality of life survey (SF-36) was administered at the time of admission and repeated at 1, 2, 4 and 12 months after injury. To determine if distinct trajectories existed for the physical component score (PCS) and the mental component score (MCS) of the SF-36, group based trajectory modeling was used (GBTM). GBTM is a semi-parametric statistical technique that identifies homogeneous subpopulations within a heterogeneous population. 

Results: 500 patients were enrolled. Follow-up was 93% at 1 month, 82% at 2 months, 70% at 4 months and 58% at 12 months. After GBTM, PCS had 3 distinct trajectories. Trajectory 1 (10.3%) is characterized by a lower baseline PCS, followed by no improvement over time. Trajectory 2 (65.6%) has a drastic decline in PCS 1 month after injury, but shows, slow consistent improvement over time. Trajectory 3 (24.1%) also has a sharp decline in PCS but has a rapid recovery and reaches near-baseline levels of health by month 12.  For the MCS, 5 trajectories were identified. Trajectory 1 (9.5%), has a low MCS at baseline and continues to have low scores throughout the rest of the study. Trajectory 2 (14.4%) has a large decrease in MCS post-injury and does not recover over the next twelve months. Trajectory 3 (22.7%) has an initial decrease in MCS early after injury, followed by continuous recovery. Trajectory 4 (19.1%) has a steady decline in MCS across most of the study. Lastly, trajectory 5 (34.3%) has consistently high MCS across all phases of recovery.

Conclusion: Both physical and mental recovery trajectories are more complex than is typically realized. There is greater variation in mental health outcomes among non-neurologically injured patients compared to physical health outcomes. The existence of multiple recovery trajectories for patients has significant implications on patient centered clinical trial design and in the distribution of limited resources devoted to recovery.

 

50.04 In Their Own Words: Improving Trauma Services For Young Men of Color

Posted on December 22, 2014

V. E. Chong1, R. N. Smith1, L. Ashley4, A. C. Marks4, T. Corbin2, J. Rich3, G. P. Victorino1  1UCSF-East Bay,Surgery,Oakland, CALIFORNIA, USA 2Drexel University College Of Medicine,Philadelphia, PA, USA 3Drexel University School Of Public Health,Philadelphia, PA, USA 4Youth ALIVE!,Oakland, CALIFORNIA, USA

Introduction:  Young men of color are disproportionately affected by interpersonal violence, which has lasting effects in the form of post-traumatic stress disorder (PTSD) and other pre-clinical symptoms of behavioral health issues. In developing services that address young men of color and their post-injury needs, their voices are often overlooked. As such, we conducted an exploratory research study using qualitative methods to investigate young men of color’s experiences with health care after suffering injury due to interpersonal violence. We aimed to identify portals of care through which young men of color seek help and to understand their relationships with these portals of care. 

Methods:  We conducted three focus group interviews with young men of color ages 18-30 using semi-structured interview guides we developed based on pertinent issues from the literature on trauma and PTSD. Focus group audiotapes were transcribed and the text was transformed to lines and stanzas. Analysis was performed via NVivo qualitative research software. The interview text was coded for recurring themes and reviewed by three study personnel. We subsequently administered a trauma symptoms screening to 69 young men of color. The screening tool was self-developed based on feedback from the focus groups and included 3 of the 4 variables in the validated Primary Care PTSD (PC-PTSD) screen. 

Results: Our focus group participants sought health care from a variety of sources. They distinguish between institutions that provide “life-saving” treatment, like trauma centers, and those that provide post-injury services, such as pain management and prescriptions. After injury, these young men often turned to “folk medicine” to treat their maladies, repeatedly describing their use of marijuana, alcohol, and cough syrup with codeine. They preferred obtaining these post-injury services through non-traditional providers, such as cannabis clubs and family members, as they described attempts to access these services at “life-saving” institutions as “a waste of time” and fraught with experiences of patient-provider misalignment. Lastly, among the young men we interviewed in the trauma symptom screening portion, 90% reported at least two symptoms of trauma, including sleep disruption, re-experiencing, focus problems, hyperarousal, and dissociation. Further, 16% of participants had screens suggestive for PTSD.  

Conclusion: Focus groups and interviews with young men of color who have been victims of violence reveal their views of the problems in their health care, their need for alternative systems of care, the disconnect between their expressed needs and the perceptions of providers, and the powerful impact of stress on their well-being. To better align our services with the expectations and needs of our patients, their concerns should be addressed and solutions integrated into quality improvement efforts.  

 

48.05 Trauma Crude Mortality is Misleading

Posted on December 22, 2014

A. J. Kerwin1, J. B. Burns1, J. H. Ra1, D. Ebler1, D. J. Skarupa1, N. Krumrei1, J. J. Tepas1  1University Of Florida,Acute Care Surgery,Jacksonville, FL, USA

Introduction: Today there is greater scrutiny of healthcare outcomes. Mortality is one quality indicator that has been used for benchmarking but there is more to mortality than meets the eye. Terminal care, percentage of penetrating trauma, patients presenting without vital signs (DOAs) and hospice discharges to can all impact a program’s mortality. Our objective was to examine the effect of this on trauma mortality.

Methods: Deidentified data from our quality management program for the years 2009- 2013 was reviewed to examine mortality as a quality indicator. We examined all deaths, death by injury type, hospice discharges, and DOAs. Chi-square analysis was performed for statistical analysis.

Results: For the period 2009- 2013 there were a total of 10,762 trauma service admits. There were 9,223 blunt trauma admits and 1,539 for penetrating trauma. There were 670 deaths during that time for an overall mortality rate of 6.2%. 480 (71.6%) deaths occurred following blunt trauma and 190 (28.4%) following penetrating trauma. Overall mortality following penetrating trauma was statistically significantly higher than after blunt trauma (11.9% vs. 5.2%; p<0.0001). During the study period there were 255 DOAs. Adding these to the overall mortality analysis increased the number of deaths by 38% and significantly increased the overall mortality rate to 8.5% (p= 0.001). During the study period there were 81 hospice discharges. Counting these patients in the mortality group gives a total of 751 deaths and significantly increases the mortality rate to 7.1% (p=0.0280).

Conclusion: Mortality is an important quality indicator for trauma programs but simply reporting crude mortality is misleading. Penetrating trauma, hospice discharges and DOAs can be important drivers of higher mortality that can reflect negatively upon a program. Hospice discharges should be included when reporting mortality. Trauma surgeons should work together to define uniform reporting of mortality as a quality indicator.

 

48.06 Prospective Evaluation of Bradycardia and Hypotension after Early Propranolol for Traumatic Brain Injury

Posted on December 22, 2014

J. Murry1, D. Hoang1, G. Barmparas1, D. Lee1, M. Bukur1, M. Bloom1, K. Inaba1, D. Margulies1, A. Salim1, E. J. Ley1  1Cedars-Sinai Medical Center,Los Angeles, CA, USA

Introduction:   Beta adrenergic receptor blockade may improve outcomes after traumatic brain injury (TBI) by modulating the subsequent cascade of immune and inflammatory changes, but its early use is not routine in part due to concern for bradycardia and hypotension. We hypothesize that judicious early propranolol after TBI (EPAT) does not alter bradycardia and hypotensive events.

Methods:   We conducted a prospective, observational study on all patients who presented with moderate to severe TBI from March 2010 to August 2013.  The first 10 patients enrolled did not receive propranolol at SICU admission (CONTROL).  Subsequent patients received propranolol at 1mg IV every 6 hours starting within 12 hours of SICU admission (EPAT) for a minimum of 48 hours.  Propranolol was held for heart rate <60bpm (bradycardia), blood pressure <90mmHg (hypotension), SICU transfer, or patient deterioration. Bradycardia and hypotensive events were recorded hourly for the first 72 hours after SICU admission.

Results:  Thirty-eight patients met enrollment criteria; 10 CONTROL and 28 EPAT.  EPAT patients received 6.6±3.9 (mean±sd) doses of propranolol.  The two cohorts were similar when compared by age>65 years, male gender, ED SBP< 90mmhg, head AIS≥4, ISS≥16 and hospital mortality (table).  ED GCS≤8 was higher in CONTROL (100% v. 35.7%, p<0.01).  Mean number of hypotensive events per patient, mean heart rate per bradycardia event, and mean blood pressure per hypotensive event were similar. The mean number of bradycardia events per patient was higher in CONTROL (mean 5.8 v. 1.6, p = 0.047).

Conclusion:  While bradycardia and hypotensive events occur early after TBI, low dose intravenous propranolol does not increase their number or severity.  Early use of propranolol after TBI appears to be safe.  Additional enrollment continues to determine if EPAT improves outcomes.

 

47.01 Age-related Mortality in Blunt Traumatic Hemorrhagic Shock: the Killers and the Life Savers

Posted on December 22, 2014

J. O. Hwabejire1, C. Nembhard1, S. Siram1, E. Cornwell1, W. Greene1  1Howard University College Of Medicine,Surgery,Washington, DC, USA

Introduction:
Hemorrhagic shock (HS) is the leading treatable cause of trauma deaths but there are sparse data on the association between age and mortality in this condition. We examined the relationship between age and mortality as well as identified the predictors of mortality in HS.

Methods:
The Glue Grant database  was analyzed. Patients aged≥16 years who sustained blunt traumatic HS were initially stratified into 8 age groups (16-24, 25-34, 35-44, 45-54, 55-64, 65-74, 75-84, 85 and above) in order to identify the mortality inflection point. For subsequent analyses, patients were stratified into: Young (16-44), Middle Age (45-64) and Elderly (65 and above). Multivariable  analysis was then used to determine predictors of mortality by group.

Results:
1976 patients were included, 66% males and 89% white, with mortality of 16%. Mortality by  initial age group are as follows: 16-24 (13.0%), 25-34 (11.9%), 35-44 (11.9%), 45-54 (15.6%), 55-64 (15.7%), 65-74 (20.3%), 75-84 (38.2%), 85 and above (51.6%), delineating 65 years as the mortality inflection point. Overall, 55% were Young, 30% Middle Age, and 15% Elderly. In the Young, survivors had lower emergency room (ER) lactate (4.4±2.5 vs. 8.0±4.3, p<0.001), Marshall’s multiple organ dysfunction score, MODS (4.8±2.4 vs. 6.8±4.1, p<0.001), and Injury Severity Score (ISS,32±13 vs. 39±14, p<0.001) than non-survivors. Predictors of mortality include MODS (OR:1.93,CI:1.62-2.30, p<0.001), ER lactate (OR:1.14,CI:1.02-1.27, p<0.022), ISS (OR:1.06,CI:1.03-1.09, p<0.001) and cardiac arrest (OR:10.60,CI:3.05-36.86, p<0.001. In Middle, survivors had lower MODS (5.0±2.3 vs. 7.3±4.2, p<0.001) and higher ER mean arterial pressure (74±41 mmHg vs. 63±43 mmHg, p=0.023) and were less likely than non-survivors to get a craniotomy (4% vs. 10%, p=0.025) or a thoracotomy (8% vs. 26%, p<0.001). Predictors of mortality in this group include MODS (OR:1.38,CI:1.24-1.53, p<0.001), cardiac arrest (OR:12.24,CI:5.38-27.81, p<0.001), craniotomy (OR:5.62,CI:1.93-16.37, p=0.002), and thoracotomy (OR:2.76,CI:1.28-5.98, p=0.010. In Elderly, survivors were slightly younger (74±7 vs. 78±7, p<0.001), had  lower MODS (5.3±2.1 vs. 6.6±3.0, p<0.001), received higher volume of prehospital hypertonic saline (1.97±0.16 L vs. 1.83 ±0.38 L, p=0.002) and were less likely to get a laparotomy (26% vs. 63%, p<0.001).  Predictors of mortality in this group include age (OR:1.07,CI:1.02-1.13, p=0.005), MODS (OR:1.47,CI:1.26-1.72, p<0.001), laparotomy (OR:2.04,CI:1.02-4.08, p=0.045) and cardiac arrest (OR:11.61,CI:4.35-30.98, p<0.001) .

Conclusion:
In blunt HS, mortality parallels increasing age, with the inflection point at 65 years. MODS and cardiac arrest uniformly predict mortality across all age groups. Open fixation of non-femur bone is uniformly protective against mortality across all age groups. Craniotomy and thoracotomy are associated with mortality in Middle Age whereas laparotomy is associated with mortality in Elderly.
 

47.02 Serum Transthyretin is a Predictor of Clinical Outcomes in Critically Ill Trauma Patients

Posted on December 22, 2014

V. Cheng1, K. Inaba1, T. Haltmeier1, A. Gutierrez1, S. Siboni1, E. Benjamin1, L. Lam1, D. Demetriades1  1University Of Southern California,Division Of Trauma And Surgical Critical Care, Department Of Surgery, LAC+USC Medical Center,Los Angeles, CA, USA

Introduction:
In surgical patients, low preoperative serum Transthyretin (TTR) level is associated with significantly longer hospital and intensive care unit (ICU) stays, higher infectious complication rates, and mortality rates.  However, the predictive value of TTR levels on outcomes after major trauma has not yet been studied.

Methods:
After IRB approval, a retrospective analysis was conducted on critically ill trauma patients admitted to the Surgical ICU at the LAC+USC Medical Center between January 2008 and May 2014.  The study included all patients who underwent a surgical procedure for trauma and had their TTR measured ≤24 hours after ICU admission.  Outcome metrics included hospital length of stay (LOS), ICU LOS, ventilator days (VD), infectious complication rate, and mortality rate.  Significance of TTR on outcome metrics was determined using univariable (Mann-Whitney U test and Fisher’s exact test) and multivariable (linear and binary logistic regressions) analyses.  In univariable analysis, patients were stratified into two TTR groups: Normal (≥19 mg/dL) and Low (<19 mg/dL).  In multivariable analysis, TTR level was maintained as a continuous variable.

Results:
348 patients met inclusion criteria (median age 36 years, 79.6% male, median Injury Severity Score 17, 71.0% blunt trauma).  The Normal and Low TTR groups consisted of 189 (54.3%) and 159 (45.7%) patients, respectively.  Compared to the Normal TTR group, the Low TTR group was associated with longer hospital LOS (median: 17 vs. 9 days, p < 0.001), longer ICU LOS (6 vs. 4 days, p < 0.001), increased VD (1 vs. 0 days, p < 0.001), higher infectious complication rates (45.3% vs. 20.1%, p < 0.001), and higher mortality rates (17.0% vs. 7.4%, p = 0.007).  Even after adjusting for age, sex, and Injury Severity Score in multivariable regression analyses, TTR level was a significant independent predictor of clinical outcomes.  Lower TTR levels were associated with longer hospital LOS (p < 0.001), longer ICU LOS (p = 0.005), increased VD (p = 0.018), higher infectious complication rates (p < 0.001), and higher mortality rates (p = 0.017).

Conclusion:
In critically ill trauma patients, low serum TTR level is associated with longer hospital LOS, longer ICU LOS, increased VD, higher infectious complication rates, and higher mortality rates.  These results warrant prospective validation of the utility of TTR levels as an outcome predictor for critically ill trauma patients.
 

47.03 Will I miss an aneurysm? The role of CTA in traumatic subarachnoid hemorrhage

Posted on December 22, 2014

K. J. Balinger1, A. Elmously1, B. A. Hoey1, C. D. Stehly1,2, S. P. Stawicki1,2, M. E. Portner1  1St Luke’s University Health Network,Level I Regional Trauma Center,Bethlehem, PA, USA 2St. Luke’s University Health Network,Department Of Research & Innovation,Bethlehem, PA, USA

Introduction: Computed tomographic angiography (CTA) tends to be over utilized in patients with traumatic subarachnoid hemorrhage (tSAH) to rule out occult aneurysmal rupture and arteriovenous malformations (AVM).  We hypothesized that there are two specific categories of patients with tSAH that are at increased risk for aneurysm/AVM and warrant targeted CTA use: (a) patients "found down" with an unknown mechanism of injury and (b) those with central subarachnoid hemorrhage (CSH) or blood in the subarachnoid cisterns and Sylvian fissures.

Methods: A retrospective analysis was performed on trauma patients with blunt head injury and tSAH who underwent CTA of the brain between January 2008 and December 2012 at a Level I Regional Trauma Center. Variables utilized in the current analysis included patient demographics, injury mechanism and severity (ISS), Glasgow Coma Scale (GCS), CTA and related radiographic studies, as well as operative interventions.  The principal outcome measure was "confirmed diagnosis" of a ruptured aneurysm/AVM.  Independent sample t-test and chi square test were used for univariate analyses. Logistic regression was utilized in multivariate analyses. Statistical significance was set at alpha = 0.05.

Results: Out of 617 patients with tSAH, 186 underwent CTA.  Mean age of the study group was 57 years, with 64% of patients being male. The mean GCS on presentation was 11±5.0, with mean ISS of 20±11.5. CTA scans were positive in 23/186 cases (12.3%) with an aneurysm found in 21 patients and an AVM in 2 patients. Findings were felt to be incidental in 15/23 patients with "positive" CTA.  Among 14/186 patients (7.5%) who were "found down" none had an aneurysm or an AVM. A total of 8 patients had a ruptured aneurysm, with 5/8 (62.5%) presenting after a fall and 3 (37.5%) presenting after an MVC.  All 8 patients with aneurysmal rupture (100%) had CSH.  None of the 81 patients with only peripheral SAH had a ruptured aneurysm/AVM. Multivariate regression analysis demonstrated that suprasellar cistern hemorrhage on CT is independently associated with aneurysm rupture (OR, 6.39; CI 1.32-30.8). Patients with a ruptured aneurysm had a significantly higher mean arterial pressure (MAP) on presentation (mean, 116±7 mmHg) than those without an aneurysm/AVM (mean, 104±18 mmHg, p<0.005). Of the 8 patients with a ruptured aneurysm, 6 patients underwent neurosurgical clipping or coiling, 1 underwent a ventriculostomy, and 1 underwent a craniotomy for evacuation of hemorrhage.

Conclusion: These preliminary data support a more selective approach to screening CTAs in patients with tSAH. CTA should be utilized in those patients with CSH regardless of mechanism of injury.  A more selective approach should be considered in those patients with only peripheral SAH. Overall cost savings would be significant.
 

47.04 CANNABIS USE HAS NEGLIGIBLE EFFECTS AFTER SEVERE INJURY

Posted on December 22, 2014

K. R. AbdelFattah1, C. R. Edwards1, M. W. Cripps1, C. T. Minshall1, H. A. Phelan1, J. P. Minei1, A. L. Eastman1  1University Of Texas Southwestern Medical Center,Burns, Trauma, And Critical Care Surgery,Dallas, TX, USA

Introduction:  Since 1996, 22 states have legalized medical marijuana (MJ) use and two have legalized recreational use.  With more states considering legislation to legalize the use of the drug, emergency responders and facilities recieving these patients need to understand the impact on acute injuries. The effects of MJ use on injured patients has not been thoroughly evaluated. Our group sought to evaluate the effects of cannabis use at the time of severe injury on hospital course and patient outcomes.

Methods:  A retrospective chart review was undertaken at an urban Level 1 Trauma Center covering a two-year period. Patients presenting with an ISS>16 were divided into four groups based on urine drug screen results. Negative urine drug screen patients represented our control group.  Positive subjects were subdivided into marijuana-only (MO), other-drugs only (OD), and mixed-use (MU) groups.  These groups were compared for differences in presenting characteristics, hospital length of stay, ICU stays, ventilator days, and death.

Results: 8441 subjects presented during the study period, of which 2134 had drug testing performed. 843(40%) had an ISS>16, with 347(41%) having negative tests (NEG). 70(14%) tested positive for marijuana only (MO), 325 (65%) for drugs other than marijuana (OD), and 103 (21%) subjects showed mixed-use (MU). Alcohol levels were higher in the MO group than any other group (p<0.05) No differences were seen in presenting GCS, ICU/hospital length of stay, ventilator days, and blood administration when comparing the MO group to the NEG group. Significant differences were found between the OD group and the NEG/MO/MU groups for presenting GCS (OD 9.7 vs NEG 11.9, MO 12.4, MU 10.7, p<0.05), ICU days (OD 6.0 vs NEG 4.7, MO 4.6, MU 3.7, p<0.05) and hospital days (OD 14.2 vs. NEG 12.0, MO 12.0, MU 10.5 p<0.05), and hospital charges (OD 182k vs. NEG 147k, MO 157k, MU 132k p<0.05).

Conclusion: Cannabis users suffering severe injury demonstrated no acute detrimental outcomes in this study compared with non-drug users. With regards to presenting GCS, ICU/hospital length of stay, and hospital charges, marijuana, alone or in combination with other drugs appeared more similar to the NEG group rather than the OD group.

 

47.05 Pre-Hospital Care And Transportation Times Of Pediatric Trauma Patients

Posted on December 22, 2014

C. J. Allen2, J. P. Meizoso2, J. Tashiro1, J. J. Ray2, C. I. Schulman2, H. L. Neville1, J. E. Sola1, K. G. Proctor2  1University Of Miami,Pediatric Surgery,Miami, FL, USA 2University Of Miami,Trauma And Critical Care,Miami, FL, USA

Introduction:  Trauma is the leading cause of death and morbidity in children in the US.  Aggressive efforts have been made to improve emergency medical transportation of injured children to major trauma centers. Still, controversy exists whether pre-hospital care improves outcomes or simply delays the necessary immediate transportation. We hypothesize that at large level 1 trauma center, with a mature pre-hospital network, pre-hospital care of severely injured children does not influence transportation time.

Methods:  From January 2000 to December 2012, consecutive pediatric admissions (≤17y) at a Level I trauma center were retrospectively reviewed for demographics, mechanisms of injury (MOI), mode of transportation, transportation times, pre-hospital interventions, injury severity score (ISS), length of stay (LOS), and survival. We analyzed pre-hospital interventions and compared transport times in survivors and non-survivors, as this cohort represents the most severely injured. Parametric data presented as mean±standard deviation and nonparametric data presented as median(interquartile range).

Results:  1,878 admitted patients were transported via emergency medical services (EMS).  Age was 11±6y with 70% male, 50% black; 76% sustained blunt injuries with an ISS of 13±12. Of these, 31% required operative intervention, LOS of 7±12, and mortality of 3.6%.  Pre-hospital care, transport times, and ISS were compared between survivors and those who died in-hospital, see Table. There were no significant differences in EMS scene to hospital arrival times between those with and without on-scene shock (27(15)min vs 27(15)min, p=NS), or between those who required on-scene intubation (32(14)min vs 27(15)min, p=NS). 

Conclusion: In the most severely injured children, those with ultimately fatal injuries, there are significantly increased rates of pre-hospital interventions, but on-scene and transportation times are not prolonged. There is no difference in pre-hospital transportation times between those with and without on-scene shock, or those requiring on-scene intubation. These results support the concept that pre-hospital interventions by skilled EMS are not associated with prolonged transportation times of critically injured pediatric trauma patients.

47.06 Trends in 1029 Trauma Deaths at a Level 1 Trauma Center

Posted on December 22, 2014

B. T. Oyeniyi1, E. E. Fox1, M. Scerbo1, J. S. Tomasek1, C. E. Wade1, J. B. Holcomb1  1University Of Texas Health Science Center At Houston,Acute Care Surgery/Surgery,Houston, TX, USA

Introduction:  Over the last decade the age of trauma patients and injury mortality has increased. At the same time, we have implemented many interventions focused on improved hemorrhage control. The objective of our study was to analyze the temporal distribution of trauma-related deaths, the factors that characterize that distribution and how those factors have changed over time at our level 1 trauma center. 

Methods:  The trauma registry, weekly Morbidity & Mortality reports and electronic medical records at Memorial Hermann Hospital in Houston, TX were reviewed.  Patients with primary burn injuries and pediatric age (<16) patients were excluded.  Two time periods (2005-2006 and 2012-2013) were included in the analysis. Baseline characteristics, time and cause of death were recorded. Mortality rates were directly adjusted for age, gender and mechanism of injury.  Results are expressed comparing 2005-2006 with 2012-2013. The Mann-Whitney and chi square tests were used to compare variables between periods, with significance set at the 0.05 level.

Results: 7080 patients including 498 deaths were examined in the early time period, while 8767 patients including 531 deaths were reviewed in the recent period.  The median age increased 6 years between the two groups, with a similar increase in those who died, 46 (28-67) to 53 (32-73) (p<0.01) years. In patients that died, no differences by gender, race or ethnicity were observed. Fall-related deaths increased from 20% to 28% (p<0.01) while deaths due to motor vehicle collisions decreased from 39% to 25% (p<0.01). Deaths associated with hemorrhage decreased from 36% to 25% (p<0.01).   26% of all deaths (including dead on arrival, DOAs) occurred within one hour of hospital arrival, while 59% occurred within 24 hours, and were similar across time periods. Unadjusted overall mortality dropped from 7.0% to 6.1% (p=0.01) and in-hospital mortality (excluding DOA) dropped from 6.0% to 5.0% (p<0.01). Adjusted overall mortality dropped 24% from 7.6% (95% CI: 6.9-8.2) to 5.8% (95% CI: 5.3-6.3) and in-hospital mortality decreased 30% from 6.6% (95% CI: 6.0-7.2) to 4.7% (95% CI: 4.2-5.1). 

Conclusion: Although US data show a 20% increase in death rate due to trauma over a similar time period, this single-site study demonstrated a significant reduction in adjusted overall and in-hospital mortality. It is possible that concentrated efforts on improving resuscitation and multiple other hemorrhage control interventions resulted in the observed reduction in hemorrhage related mortality. Most trauma deaths continue to be concentrated very soon after injury. We observed an aging trauma population and an increase in deaths due to falls. These changing factors provide guidance on potential future prevention and intervention efforts. 

 

47.07 The Economic Burden Of Care For Severe Work Related Injuries In A Level-One Trauma Referral Centre

Posted on December 22, 2014

C. T. Robertson-More1, B. Wells1,2, D. Nickerson3, A. Kirkpatrick1,2, C. Ball1,2  1University Of Calgary,General Surgery,Calgary, AB, Canada 2University Of Calgary,Trauma Surgery,Calgary, AB, Canada 3University Of Calgary,Plastic Surgery,Calgary, AB, Canada

Introduction: Work-related injuries (WRI) are common and represent a significant logistical and economic burden to health care systems. It is also possible that insurers and/or public health care systems do not account for the potentially higher cost of caring for these patients when compared to patients with non-WRI (NWRI). The primary aim of this study was to evaluate the demographics, volume, costs and outcomes associated with WRI at a high volume trauma center.

Methods: The Alberta Trauma Registry and clinical information system were used to perform a retrospective cohort study describing all patients with severe WRI (ISS>12) admitted to a high volume, tertiary care trauma referral center between April, 1995 and March, 2013. Patients who died within the emergency department were excluded. Standard statistical methodology was utilized (p<0.05).

Results: Of 14,964 total trauma admissions, 1,270 (8.5%) were for severe WRI. Overall, the patients’ mean age was 45 years with a male to female ratio of 2.8:1 and mean Injury Severity Score (ISS) of 22.7. Blunt (94%), penetrating (4%), and burn (2%) injury mechanisms were observed. Compared to patients with NWRI, the WRI group was significantly younger (41 vs. 46 years, 95% CI: -5.7 to -3.9yrs), typically male (94% vs. 72%, p<0.05), and had fewer pre-injury comorbidities (p<0.05). Although they displayed statistically equivalent ISS, the WRI group had a greater length of stay in the intensive care unit (2.8 vs. 2.3 days, 95% CI: 0.06 to 0.86 days), length of mechanical ventilation (2.2 vs. 1.8 days, 95% CI: 0.08 to 0.68 days), and mean number of surgical/operative procedures (0.86 vs. 0.67 per patient, 95% CI: 0.11 to 0.27). In contrast, significantly fewer patients with WRI died while in hospital (8% vs. 12%, p<0.05). Consequently, more patients with WRI were discharged home without support services (62% vs. 57%, p<0.05) and significantly fewer were transferred to long-term care facilities (0.5 vs. 1%, p<0.05). The acute care economic burden of patients with WRI was significantly higher (p<0.05). Increased costs were related to the care of these patients in the intensive care unit (p<0.05) and operating theatre (p<0.05), as well as for physician compensation (p<0.05).

Conclusion: Patients with WRI admitted to our trauma center were younger, less comorbid, more likely male and had a significantly higher utilization of acute care resources despite a similar ISS when compared to those with NWRI. These increased costs and economic burden in critical care, operative and physician based services are not recovered from work place insurers in public health care systems.

47.08 Successful Observation of Small Traumatic Pneumothoraces in Patients Requiring Aeromedical Transfer

Posted on December 22, 2014

N. Lu1, C. Ursic1, H. Penney1,2, S. Steinemann1, S. Moran1  1University Of Hawaii,Department Of Surgery,Honolulu, HI, USA 2University Of Hawaii,Department Of Radiology,Honolulu, HI, USA

Introduction:  With the widespread use of computed tomography (CT) imaging, the occult pneumothorax (PTX) has become a common finding. It has been shown that it is safe to monitor occult PTX in stable patients, even if they are on positive pressure ventilation. Observation of occult PTX without chest tube placement has been supported for those seen on CT to be <7mm measured perpendicular from lung to chest wall. However, patients transported by air are not optimally monitored and not in the care of practitioners skilled in thoracostomy tube placement.

Methods:  We undertook a retrospective chart review of patients with traumatic PTX who were transported by air over the course of three years (2010-2012) to a level II trauma center that serves 1.3 million people. Occult PTX was defined as a pneumothorax that was not visible on chest radiograph (CXR), but was visible on CT imaging. Patients who did not have an overt PTX or a clinical reason for immediate chest tube placement were divided into two groups: those with PTX<7mm and those with PTX>7 mm.

Results: From 2010 to 2012, 66 patients were transferred with a total of 83 PTX. Eleven PTX in 8 patients were treated with chest tubes placed for clinical reasons such as CPR or needle decompression in the field. For 11 PTX, we have no information about pre-transport CXR or were unable to measure the PTX on CT. Eleven overt PTX were treated with thoracostomy tubes. Of the 10 large occult (>7mm) PTX, 8 were treated with thoracostomy tubes and two were treated with observation in transport. Of the 39 small (<7mm) PTX, 19 were treated with thoracostomy tubes (15 ventilated, 4 not ventilated); and 20 were observed during transportation (5 ventilated, 15 not ventilated). Of all patients without thoracostomy tubes prior to transport, 3 were placed on arrival. One was placed in a patient whose repeat CXR showed the PTX (no longer occult), though the patient was stable.  One was placed in a patient whose follow up CT showed expansion to 8mm and who was to be intubated for an operation. One was placed in a patient with a pre-transfer PTX>7 mm and with copious subcutaneous emphysema which expanded en route. There were 15 total complications. Thirteen were malpositioned and two were related to empyema requiring thoracoscopic drainage.

Conclusion: Patients with small PTX can safely be transported by air without thoracostomy tubes. Only one of 20 patients sent without a chest tube required immediate chest tube placement and, in retrospect, it would have been recommended that a tube be placed prior to transport due to the size of the PTX and the amount of subcutaneous air. Mechanical ventilation prompted more thoracostomy tube placements.  In addition, observation may reduce complications from chest tube placement (malposition, infection, increased number of CXR, increase in hospital length of stay, and delay in returning home). Further studies with large numbers of patients are warranted.

47.09 Unplanned Intensive Care Unit Admissions Following Trauma

Posted on December 22, 2014

J. A. Rubano1, J. A. Vosswinkel1, J. E. McCormack1, E. C. Huang1, M. Paccione1, R. S. Jawa1  1Stony Brook University Medical Center,Trauma,Stony Brook, NY, USA

Introduction: Unplanned Intensive Care Unit (UP-ICU) admission is a key quality measure of the American College of Surgeons Committe on Trauma. We sought to evaluate frequency, timing, risk factors, and morbidity associated with unplanned ICU admission following acute traumatic injury.

Methods: Retrospective analysis of a state-designated level I trauma center's registry.  All adult trauma admissions from January 2007 through December 2013 were considered.  Burns, isolated hip fractures, field/emergency department intubations and patients takend directly to the operating room were excluded.  Univariate and multivariate statistical analyses were performed; p≤ 0.05 was considered significant.

Results: Of 5465 patients meeting study criteria, 85.2% required no ICU (NO-ICU) stay, 10.9% had planned (PL-ICU) admission, and 3.9% were UP-ICU admissions.  Patient demographics are presented in the table.  UP-ICU admissions more frequently had ≥2 National Trauma Data Standard comorbid conditions (65.1%) than NO-ICU (33.2%) and PL-ICU admissions (47.2%), p<0.05. Median length of stay prior to UP-ICU admission was significantly longer than PL-ICU admission (2 days, IQR 0-4 vs. 0 days, IQR 0-0).  UP-ICU admissions had significantly more frequent strokes (2.4% vs 0.5%), MI (14.2% vs. 4.0%), respiratory failure (10.9% vs. 1.7%), pneumonia (30.2% vs. 9.9%), renal failure (7.6% vs. 2.7%), sepsis (10.9% vs. 2.9%), and DVT/PE (11,8% vs. 5.2%) as compared to PL-ICU admissions.  Rates of these complications in the NO-ICU group were each ≤1.1% and correspondingly significantly less than in UP-ICU group.  Finally, UP-ICU patients had a higher mortality (18.4%) than NO-ICU (0.49%, p<0.001) or PL-ICU admission groups (5.71%, p < 0.001).  In subsequent multivariate logistic regression, risk factors for unplanned ICU admission were respiratory failure (odds ratio 3.74, 95% confidence interval 1.62-8.63), PE/DVT (2.27, 1.23-4.18), MI (1.98, 1.05-3.74), and pneumonia (2.60, 1.66-4.08).  Age, presence of ≥ 2 comorbidities, sepsis, and stroke were not risk factors. ISS was slightly negatively associated with UP-ICU admission (OR 0.97 (95% CI 0.95 – 0.99).

Conclusion: Unplanned ICU admission is an infrequent but morbid event. It is associated with a threefold increase in mortality as compared to planned ICU admission.  A slightly lower ISS in UP-ICU would be expected as these patients were not directly admitted to the ICU.  Earlier identification of risk factors may decrease unplanned ICU admission.
 

47.10 Analysis of the Coagulation System in Burn Patients: Perhaps Not As Simple As INR

Posted on December 22, 2014

S. Tejiram1, K. Brummel-Ziedins3, T. Orfeo3, S. Butenas3, B. Hamilton2, J. Marks2, L. Moffatt2, J. Shupp1,2  1MedStar Washington Hospital Center,The Burn Center, Department Of Surgery,Washington, DC, USA 2MedStar Health Research Institute,Firefighters’ Burn And Surgical Research Laboratory,Washington, DC, USA 3University Of Vermont,Department Of Biochemistry,Colchester, VT, USA

Introduction: While a body of literature exists on coagulopathy in trauma patients, understanding of abnormal coagulation in burn patients is limited. Studies have shown alterations in antithrombin, protein C and S levels after burn, but controversy remains over whether burn injury induces coagulopathy. There is no consensus on whether burn patients with variable injury severity are at risk for hyper- or hypocoagulation. Coagulation is a complex process that is frequently assessed only by laboratory values such as PT, PTT, and INR. These measurements do not account for clotting factor dynamics or clot characteristics. Real time assessment of a patient’s coagulation profile may help clinicians better understand the pathophysiology underlying abnormal coagulation in burn patients. Here, we monitored clotting factor levels in a pilot group of burn patients for 96 hours after admission to study potential perturbations in the coagulation system and help elucidate potentially meaningful dynamics in coagulation after burn injury not indicated by INR alone.

Methods: Nine thermally injured patients with total body surface area injuries of 25% or greater who presented to a verified burn center between 2013 and 2014 were included for analysis. Citrated plasma was collected at admission and at regular intervals over a 96 hour period. Clinical laboratory information, specifically PT, PTT, and INR, collected over the same time was compared to levels of factors II, IIa, V, VII, VIII, IX, IXa, X, XI, XIa, antithrombin, and tissue factor pathway inhibitor measured in plasma.

Results: Of the patients profiled, 4 died and 5 survived. Seven patients had factor VIII levels beyond the upper limit of normal range upon admission. Four of these had factor VIII levels 2-3 fold higher than normal. Over the subsequent 24 hours, all patients experienced an initial decrease of factor VIII levels to normal ranges before increasing again above the normal range. Factor IX was also elevated approximately 1.5 times normal levels upon admission in all patients and remained above normal range for all but 2 patients. Conversely, factor VII levels decreased below normal ranges for 3 patients after 24 hours. Only 4 patients had antithrombin levels in normal range upon admission and all patients had antithrombin levels below normal range shortly thereafter for the subsequent 96 hours. Three patients showed an increase in INR and PTT beyond normal range. Clinical laboratory values of INR and PTT remained within normal limits (INR < 1.3 and PTT 23-45s) for all other patients during this 96 hour period.

Conclusion: Dynamic changes in clotting factor levels follow immediately after thermal injury that may not be detected by monitoring of INR and PTT alone. These changes may be important in early identification of coagulopathy in this patient population, which to date is poorly characterized. Further study is warranted to explore the scope of abnormal coagulation in burn patients.

 

44.10 Combined Treatment with Hypothermia and Valproate Upregulates Survival Pathway in Hemorrhagic Shock

Posted on December 22, 2014

T. Bambakidis1, S. E. Dekker1, B. Liu1, J. Maxwell1, K. T. Chtraklin1, D. Linzel1, W. He1, Z. Chang1, Y. Li1, H. B. Alam1  1University Of Michigan,Surgery,Ann Arbor, MI, USA

Introduction: Therapeutic hypothermia and valproic acid (VPA, a histone deacetylase inhibitor) have independently been shown to be protective in models of trauma and hemorrhagic shock, but require logistically challenging doses to be effective. Theoretically, combined treatment may further enhance effectiveness, allowing us to use lower doses of each modality. We previously confirmed the beneficial effects of combined therapy in an in vitro model of hypoxic neuronal cells. The aim of this study was to determine whether combined Hypothermia+VPA treatment offers better cytoprotection compared to individual treatments in an in vivo hemorrhage model.

Methods: Male Sprague-Dawley rats were subjected to 40% volume-controlled hemorrhage, kept in shock for 30 minutes, and assigned to one of the following treatment groups: normothermia (36-37°C), Hypothermia (30±2°C), normothermia+VPA (300mg/kg), and Hypothermia+VPA (n=5/group). After three hours of observation, the animals were sacrificed, liver tissue was harvested and subjected to whole cell lysis, and levels of key proteins in the pro-survival Akt pathway were measured using Western Blot.

Results: Levels of pro-apoptotic protein (cleaved caspase-3) were significantly lower, and pro-survival proteins (Bcl-2 and β-catenin) significantly higher in the Hypothermia+VPA group compared to the individual treatments (P<0.05) (Figure). The level of the downstream protein Phospho-GSK-3β was significantly higher in the hypothermia and combined treatment groups (P<0.001).

Conclusion: This is the first in-vivo study to demonstrate that combined treatment with VPA and hypothermia offers better cytoprotection than these treatments given independently.

 

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