Propranolol attenuates cognitive, learning, and memory deficits in a murine model of traumatic brain injury.

BACKGROUND: ß-blockers have been shown to improve survival after traumatic brain injury (TBI); however, the impact of continuous dosage of ß-blockers on cognitive function has not been elucidated. We hypothesized that a daily dose of propranolol can improve memory, learning, and cognitive function following TBI. STUDY DESIGN: Twenty male C57BL mice were subjected to a cortical-controlled moderate TBI. Two hours after TBI, animals were randomly allocated to either the ß-blocker group (n = 10) or the placebo group (n = 10). Mice in the ß-blocker group received intraperitoneal 4 mg/kg propranolol every 24 hours for 7 days while the placebo group received 4 mg/kg normal saline. Baseline novel object recognition and classic maze tests were done prior to TBI and then daily from Day 1 through 7 after TBI. Animals were sacrificed on Day 7. Serum biomarkers were measured using ELISA and brain sections were analyzed using western blot and hematoxylin and eosin staining. RESULTS: Both the ß-blocker and placebo groups had lower recognition index scores compared with the baseline following TBI. ß-blocker mice had significantly higher novel object recognition scores compared with placebo mice 2 days after TBI. The ß-blocker group required less time to complete the maze-test compared to placebo group after Day 4. There was no difference regarding the serum levels of IL-1ß, IL-6, and TNF-α. The ß-blocker group had lower levels of UCHL-1 and higher levels of Hsp-70 in brain lysate. Hematoxylin and eosin staining revealed that more neurons in the hippocampal-CA1 area underwent apoptosis in the placebo group compared with the ß-blocker group. CONCLUSION: Postinjury propranolol administration results in improved memory, learning and cognitive functions in a murine model of moderate TBI. Propranolol increases the expression of antiapoptotic protein (Hsp-70) and decreases cell death in the hippocampal-CA1 area compared with the placebo.

Four-factor prothrombin complex concentrate is associated with improved survival in trauma-related hemorrhage: A nationwide propensity-matched analysis.

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

Severely injured trauma patients with admission hyperfibrinolysis: Is there a role of tranexamic acid? Findings from the PROPPR trial.

INTRODUCTION: Administration of tranexamic acid (TXA) in coagulopathy of trauma gained popularity after the CRASH-2 trial. The aim of our analysis was to analyze the role of TXA in severely injured trauma patients with admission hyperfibrinolysis. METHODS: We reviewed the prospectively collected Pragmatic, Randomized Optimal Platelet and Plasma Ratios database. We included patients with admission hyperfibrinolysis (Ly30 >3%) on thromboelastography. Patients were stratified into two groups (TXA and No-TXA) and were matched in 1:2 ratio using propensity score matching for demographics, admission vitals, and injury severity. Primary outcome measures were 6-, 12-, and 24-hour and 30-day mortality; 24-hour transfusion requirements; time to achieve hemostasis; and rebleeding after hemostasis requiring intervention. Secondary outcome measures were thrombotic complications. RESULTS: We analyzed 680 patients. Of those, 118 had admission hyperfibrinolysis, and 93 patients (TXA: 31 patients; No-TXA: 62 patients) were matched. Matched groups were similar in age (p = 0.33), gender (p = 0.84), race (p = 0.81), emergency department (ED) Glasgow Coma Scale (p = 0.34), ED systolic blood pressure (p = 0.28), ED heart rate (p = 0.43), mechanism of injury (p = 0.45), head Abbreviated Injury Scale score (p = 0.68), injury severity score (p = 0.56), and blood products ratio (p = 0.44). Patients who received TXA had a lower 6-hour mortality rate (34% vs. 13%, p = 0.04) and higher 24-hour transfusion of plasma (15 vs. 10 units, p = 0.03) compared with the No-TXA group. However, there was no difference in 12-hour (p = 0.24), 24-hour (p = 0.25), and 30-day mortality (p = 0.82). Similarly, there was no difference in 24-hour transfusion of RBC (p = 0.11) or platelets (p = 0.13), time to achieve hemostasis (p = 0.65), rebleeding requiring intervention (p = 0.13), and thrombotic complications (p = 0.98). CONCLUSION: Tranexamic acid was associated with increased 6-hour survival but does not improve long-term outcomes in severely injured trauma patients with hemorrhage who develop hyperfibrinolysis. Moreover, TXA administration was not associated with thrombotic complications. Further randomized clinical trials will identify the subset of trauma patients who may benefit from TXA. LEVEL OF EVIDENCE: Therapeutic study, level III.

The role of four-factor prothrombin complex concentrate in coagulopathy of trauma: A propensity matched analysis.

BACKGROUND: Coagulopathy is a common complication after severe trauma. The efficacy of 4-factor prothrombin complex concentrate (4-PCC) as an adjunct to fresh frozen plasma (FFP) in reversal of coagulopathy of trauma (COT) has not been studied. The aim of our study is to compare 4-PCC + FFP versus FFP alone for the treatment of COT. METHODS: We reviewed all trauma patients older than 18 years who received PCC + FFP or FFP alone at our Level I trauma center from 2015 to 2016. We excluded patients on preinjury oral anticoagulants. Patients were divided into two groups (4-PCC + FFP: FFP alone) and were matched in a 1:2 ratio using propensity score matching for demographics, vital and injury parameters, and initial international normalized ratio (INR). COT was defined as admission INR > 1.5. Corrected INR was defined as an INR of 1.5 or less. Outcome measures were time to correction of INR, packed red blood cells units transfused, thromboembolic complications, and mortality. RESULTS: We analyzed 516 trauma patients, of which 120 patients (4-PCC + FFP: 40, FFP: 80) were matched. Mean age was 58 ± 20 years; 60% were male, median Injury Severity Score was 29 (14-38). Mechanism of injury was blunt in 87% patients. 4-PCC + FFP was associated with an accelerated correction of INR (373 minutes vs. 955 minutes; p = 0.001), a decrease in packed red blood cells units (7 units vs. 9 units; p = 0.04), and FFP units (5 units vs. 7 units; p = 0.03) transfused compared to FFP alone. 4-PCC + FFP was associated with a lower mortality (25% vs. 33% p = 0.04) compared with FFP alone; however, there was no difference in the thromboembolic complications (2.5% vs. 1.2%, p = 0.5) between the two groups. Administration of PCC + FFP led to an earlier correction of the INR compared with FFP alone. CONCLUSION: Results of our study demonstrated that the use of 4-PCC in conjunction with FFP is associated with the rapid reversal of INR and reduction in transfusion requirements as compared with FFP alone. Four-factor PCC as a component therapy along with FFP is superior to FFP alone for the reversal of COT. LEVEL OF EVIDENCE: Therapeutic studies, level IV.

Decompressive craniectomy versus craniotomy only for intracranial hemorrhage evacuation: A propensity matched study.

BACKGROUND: Decompressive craniectomy (DC) is often performed in conjunction with evacuation of intracranial hemorrhage (ICH) to control intracranial pressure (ICP) in patients with a traumatic brain injury (TBI). The efficacy of DC in lowering ICP is well established; however, its effect on clinical outcomes remains controversial. The aim of our study is to assess outcomes in TBI patients undergoing DC versus craniotomy only (CO) for the evacuation of ICH. METHODS: We performed a 5-year retrospective analysis of TBI patients with ICH who underwent craniotomy or craniectomy for traumatic ICH. Patients were divided into two groups, those who underwent CO and those who underwent DC. Propensity scoring matched patients in a 1:2 ratio for demographics, admission Glasgow Coma Scale (GCS) score, severity of injury, type and size of ICH, and anticoagulant use. Outcome measures included mortality, adverse discharge disposition (skilled nursing facility), discharge GCS and Glasgow Outcome Scale scores, and complications. RESULTS: We reviewed 1,831 patients with TBI, of which 155 underwent craniotomy and/or craniectomy. After propensity score matching, we included 99 of those patients in our study (DC, 33; CO, 66). Matched groups were similar in age (p = 0.68), admission GCS score (p = 0.50), Injury Severity Score (p = 0.70), head Abbreviated Injury Scale score (p = 0.32), and intracranial bleeding characteristics. Overall, 26.3% (n = 26) of the patients died and 62.6% (n = 62) were discharged to Rehab/skilled nursing facility. There was no difference in the mortality rate (27.3% vs. 25.0%; p = 0.99), adverse discharge disposition (45% vs. 33%; p = 0.66), GCS score (p = 0.53), and Glasgow Outcome Scale (p = 0.80) at discharge between the DC and the CO groups. However, patients in DC group had higher complication rates and ventilator days. CONCLUSION: This study showed no significant difference in clinical outcomes for patients undergoing evacuation of ICH regardless of the procedure performed. DC did not appear to be superior to craniotomy alone for the treatment of acute ICH. LEVEL OF EVIDENCE: Therapeutic, level III.

Every minute counts: Time to delivery of initial massive transfusion cooler and its impact on mortality.

BACKGROUND: American College of Surgeons Trauma Quality Improvement Best Practices recommends initial massive transfusion (MT) cooler delivery within 15 minutes of protocol activation, with a goal of 10 minutes. The current study sought to examine the impact of timing of first cooler delivery on patient outcomes. METHODS: Patients predicted to receive MT at 12 Level I trauma centers were randomized to two separate transfusion ratios as described in the PROPPR trial. Assessment of Blood Consumption score or clinician gestalt prediction of MT was used to randomize patients and call for initial study cooler. In this planned subanalysis, the time to MT protocol activation and time to delivery of the initial cooler were evaluated. The impact of these times on mortality and time to hemostasis were examined using both Wilcoxon rank sum and linear and logistic regression. RESULTS: Among 680 patients, the median time from patient arrival to MT protocol activation was 9 minutes with a median time from MT activation call to delivery of first cooler of 8 minutes. An increase in both time to MT activation and time to arrival of first cooler were associated with prolonged time to achieving hemostasis (coefficient, 1.09; p = 0.001 and coefficient, 1.16; p < 0.001, respectively). Increased time to MT activation and time to arrival of first cooler were associated with increased mortality (odds ratio [OR], 1.02; p = 0.009 and OR, 1.02; p = 0.012, respectively). Controlling for injury severity, physiology, resuscitation intensity, and treatment arm (1:1:1 vs. 1:1:2), increased time to arrival of first cooler was associated with an increased mortality at 24 hours (OR, 1.05; p = 0.035) and 30 days (OR, 1.05, p = 0.016). CONCLUSION: Delays in MT protocol activation and delays in initial cooler arrival were associated with prolonged time to achieve hemostasis and an increase in mortality. Independent of products ratios, every minute from time of MT protocol activation to time of initial cooler arrival increases odds of mortality by 5%. LEVEL OF EVIDENCE: Prognostic, level II; Therapeutic, level III.

Damage control laparotomy utilization rates are highly variable among Level I trauma centers: Pragmatic, Randomized Optimal Platelet and Plasma Ratios findings.

BACKGROUND: Damage control laparotomy (DCL) is intended to limit deleterious effects from trauma-induced coagulopathy. DCL has been associated with mortality reduction, but may increase complications including sepsis, abscess, respiratory failure, hernia, and gastrointestinal fistula. We hypothesized that (1) DCL incidence would vary between institutions; (2) mortality rates would vary with DCL rates; (3) standard DCL criteria of pH, international normalized ratio, temperature and major intra-abdominal vascular injury would not adequately capture all patients. METHODS: Trauma patients at 12 Level 1 North American trauma centers were randomized based on transfusion ratios as described in the Pragmatic, Randomized Optimal Platelet and Plasma Ratios trial. We analyzed outcomes after emergent laparotomy using a mixed-effects logistic model comparing DCL versus definitive surgical management with random effect for study site. Primary outcomes were 24-hour and 30-day mortality. RESULTS: Three hundred twenty-nine patients underwent emergent laparotomy: 213 (65%) DCL and 116 (35%) definitive surgical management. DCL rates varied between institutions (33-83%), (p = 0.002). Median Injury Severity Score (ISS) was higher in the DCL group, 29 (interquartile range, 13-34) versus 21 (interquartile range, 22-41) (p < 0.001). Twenty-four-hour mortality was 19% with DCL versus 4% (p < 0.001); 30-day mortality was 28% with DCL versus 19% (p < 0.001). In a mixed-effects model, ISS and major intra-abdominal vascular injury were correlates of DCL (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.02-1.07 and OR, 2.7; 95% CI, 1.4-5.2). DCL was not associated with 30-day mortality (OR, 2.33; 95% CI, 0.97-5.60). Correlates included ISS (OR, 1.06; 95% CI, 1.02-1.09), PRBCs in 24 hours (OR, 1.10; 95% CI, 1.03-1.18), and age (OR, 1.04; 95% CI, 1.01-1.06). No significant mortality difference was detected between institutions (p = 0.63). Sepsis and VAP occurred more frequently with DCL (p < 0.05). Eighty percent (135/213) of DCL patients met standard criteria. CONCLUSION: Although DCL utilization varied significantly between institutions, there was no significant mortality difference between centers. This finding suggests tempering DCL use may not decrease mortality, but could decrease related complications. LEVEL OF EVIDENCE: Therapeutic study, level III.

Improving mortality in trauma laparotomy through the evolution of damage control resuscitation: Analysis of 1,030 consecutive trauma laparotomies.

BACKGROUND: The aim of this study was to evaluate the related change in outcomes (mortality, complications) in patients undergoing trauma laparotomy (TL) with the implementation of damage control resuscitation (DCR). We hypothesized that the implementation of DCR in patients undergoing TL is associated with better outcomes. METHODS: We analyzed 1,030 consecutive patients with TL. Patients were stratified into three phases: pre-DCR (2006-2007), transient (2008-2009), and post-DCR (2010-2013). Resuscitation fluids (crystalloids and blood products), injury severity score (ISS), vital signs, and laboratory (hemoglobin, international normalized ratio, lactate) parameters were recorded. Regression analysis was performed after adjusting for age, ISS, laboratory and vital parameters, comorbidities, and resuscitation fluids to identify independent predictors for outcomes in each phase. RESULTS: Patient demographics and ISS remained the same throughout the three phases. There was a significant reduction in the volume of crystalloid (p = 0.001) and a concomitant increase in the blood product resuscitation (p = 0.04) in the post-DCR phase compared to the pre-DCR and transient DCR phases. Volume of crystalloid resuscitation was an independent predictor of mortality in the pre-DCR (OR [95% CI]: 1.071 [1.03-1.1], p = 0.01) and transient (OR [95% CI]: 1.05 [1.01-1.14], p = 0.01) phases; however, it was not associated with mortality in the post-DCR phase (OR [95% CI]:1.01 [0.96-1.09], p = 0.1). Coagulopathy (p = 0.01) and acidosis (p = 0.02) were independently associated with mortality in all three phases. CONCLUSION: The implementation of DCR was associated with improved outcome in patients undergoing TL. There was a decrease in the use of damage control laparotomy, with a decrease in the use of crystalloid and an increase in the use of blood products. LEVEL OF EVIDENCE: Prognostic study, level III.

The impact of patient protection and Affordable Care Act on trauma care: A step in the right direction.

INTRODUCTION: The Patient Protection and Affordable Care Act (ACA) was implemented to guarantee financial coverage for health care for all Americans. The implementation of ACA is likely to influence the insurance status of Americans and reimbursement rates of trauma centers. The aim of this study was to assess the impact of ACA on the patient insurance status, hospital reimbursements, and clinical outcomes at a Level I trauma center. We hypothesized that there would be a significant decrease in the proportion of uninsured trauma patients visiting our Level I trauma center following the ACA, and this is associated with improved reimbursement. METHODS: We performed a retrospective analysis of the trauma registry and financial database at our Level I trauma center for a 27-month (July 2012 to September 2014) period by quarters. Our outcome measures were change in insurance status, hospital reimbursement rates (total payments/expected payments), and clinical outcomes before and after ACA (March 31, 2014). Trend analysis was performed to assess trends in outcomes over each quarter (3 months). RESULTS: A total of 9,892 patients were included in the study. The overall uninsured rate during the study period was 20.3%. Post-ACA period was associated with significantly lower uninsured rate (p < 0.001). During the same time, there was as a significant increase in the Medicaid patients (p = 0.009). This was associated with significantly improved hospital reimbursements (p < 0.001).On assessing clinical outcomes, there was no change in hospitalization (p = 0.07), operating room procedures (p = 0.99), mortality (p = 0.88), or complications (p = 0.20). Post-ACA period was also not associated with any change in the hospital (p = 0.28) or length of stay at intensive care unit (p = 0.66). CONCLUSION: The implementation of ACA has led to a decrease in the number of uninsured trauma patients. There was a significant increase in Medicaid trauma patients. This was associated with an increase in hospital reimbursements that substantially improved the financial revenues. Despite the controversies, implementation of ACA has the potential to substantially improve the financial outcomes of trauma centers through Medicaid expansion. LEVEL OF EVIDENCE: Economic and value-based evaluation, level III.

Injury prevention programs against distracted driving among students.

BACKGROUND: Motor vehicle crashes are the leading cause of death and nonfatal injury among young adults. The aims of this study were to assess the magnitude of distracted driving (DD) among students and to examine the effectiveness of awareness campaign against DD. We hypothesized that DD is prevalent among students and educational efforts such as DD awareness campaign can effectively reduce it. METHODS: This study was conducted within the University of Arizona that has a student enrollment of 42,000 students. We conducted our prospective interventional study in four phases at the university campus. Phase 1 involved 1-week preintervention observation, Phase 2 involved 1-week intervention, Phase 3 involved 1-week postintervention observation, and Phase 4 involved 1-week 6-month postintervention observation. We used a combination of e-mails, pamphlets, interactive sessions, and banners as intervention tools in student union. Our primary outcome was the prevalence of DD before, after, and 6 months after intervention. RESULTS: A total of 47,764 observations (before, 14,844; after, 17,939; 6 months after, 14,981) were performed. During the study period, overall rate of DD rate among the students was 8.8 (5.4) per 100 drivers (texting, 4.8 [3.7] per 100 drivers; talking, 3.9 [2.0] per 100 drivers).The baseline rate of DD among students during the phase one was 9.0 (1.2) per 100 drivers (texting, 4.8 [1.7] per 100 drivers; talking, 4.1 [1.1] per 100 drivers). Following intervention, there was a 32% significant reduction in overall DD (9.0 [1.2] vs. 6.1 [1.7], p < 0.001) in the immediate postintervention phase; however, the rate of DD returned to baseline at 6 months after intervention and trended toward increase (9.0 [1.2] vs. 11.1 [8.4], p = 0.34). CONCLUSION: DD is prevalent among university students. Following a comprehensive preventive campaign against DD, there was a 32% reduction in the rate of DD in the immediate postintervention period. However, a single episode of intervention did not have a sustainable preventive effect on the DD, and the rate increased to the baseline at 6-month follow-up. Targeting DD with a successful injury prevention campaign with repeated boosters may decrease its prevalence among the students.

Changing paradigms in the management of 2184 patients with traumatic brain injury.

OBJECTIVES: The aim of this study was to assess the change in trends in the management of traumatic brain injury (TBI) at a level I trauma center and the utilization of resources as a result of this change in management. BACKGROUND: The management of TBI has been evolving with trends toward management of minimally injured patients with intracranial hemorrhage exclusively by trauma surgeons. METHODS: A 5-year (2009-2014) prospective database on all patients with TBI (skull fracture/intracranial hemorrhage on head computed tomography) presenting to a level I trauma center was analyzed for patient demographics, injuries, admission physiology, computed tomographic scan results, and hospital outcomes. These records were matched to the institutional registry and hospital financial database. RESULTS: A total of 2184 patients were included with median (interquartile range) Glasgow Coma Scale score of 15 (12-15), and median (interquartile range) head-abbreviated injury scale score of 3 (2-4). The distribution of types and size of intracranial bleeds remained unchanged throughout the study period. The proportion of TBI managed exclusively by trauma surgeons increased significantly over the years from 6.8% to 40.1% (P < 0.001). Proportion of patients who received neurosurgical consultations (P < 0.001) and repeat head computed tomographic scans (P < 0.001), hospital length of stay (P = 0.028), and costs (P < 0.001) decreased significantly over time. The overall mortality rate (18.5%) and rate of intervention (14.1%) remained unchanged. CONCLUSIONS: TBI patients can be selectively managed without initially involving neurosurgeons safely in a cost-effective manner, resulting in more effective use of precious resources.

Use of prothrombin complex concentrate as an adjunct to fresh frozen plasma shortens time to craniotomy in traumatic brain injury patients.

BACKGROUND: The use of prothrombin complex concentrate (PCC) to reverse acquired (coagulopathy of trauma) and induced coagulopathy (preinjury warfarin use) is well defined. OBJECTIVE: To compare outcomes in patients with traumatic brain injury without warfarin therapy receiving PCC as an adjunct to fresh frozen plasma (FFP) therapy compared with patients receiving FFP therapy alone. METHODS: All patients with traumatic brain injury coagulopathy without warfarin therapy who received PCC (25 IU/kg) in conjunction with FFP or FFP alone at our Level I trauma center were reviewed. Coagulopathy was defined as an international normalized ratio >1.5. The groups (PCC + FFP vs FFP alone) were matched using propensity score matching on a 1:2 ratio for age, sex, Glasgow Coma Scale score, Injury Severity Score, head Abbreviated Injury Scale score, and international normalized ratio (INR) on presentation. The primary outcome measure was time to craniotomy. Secondary outcome measures were blood product requirements, cost of therapy, and mortality. RESULTS: A total of 1641 patients were reviewed, 222 of whom were included (PCC + FFP, 74; FFP, 148). The mean ± standard deviation age was 46.4 ± 21.7 years, the median (range) Glasgow Coma Scale score was 8 (3-12), and the mean ± standard deviation INR on presentation was 1.92 ± 0.6. PCC + FFP therapy was associated with an accelerated correction of INR (P = .001) and decrease in overall pack red blood cell (P = .035) and FFP (P = .041) administration requirement. Craniotomy was performed in 26.1% of patients (n = 58). Patients who received PCC + FFP therapy had faster time to craniotomy (P = .028) compared with patients who received FFP therapy alone. CONCLUSION: PCC as an adjunct to FFP decreases the time to craniotomy with faster correction of INR and concomitant decrease in the need for blood product requirement in patients with traumatic brain injury exclusive of prehospital warfarin therapy.