Decreasing adrenergic or sympathetic hyperactivity after severe traumatic brain injury using propranolol and clonidine (DASH After TBI Study): study protocol for a randomized controlled trial

BACKGROUND: Severe TBI, defined as a Glasgow Coma Scale ≤ 8, increases intracranial pressure and activates the sympathetic nervous system. Sympathetic hyperactivity after TBI manifests as catecholamine excess, hypertension, abnormal heart rate variability, and agitation, and is associated with poor neuropsychological outcome. Propranolol and clonidine are centrally acting drugs that may decrease sympathetic outflow, brain edema, and agitation. However, there is no prospective randomized evidence available demonstrating the feasibility, outcome benefits, and safety for adrenergic blockade after TBI. METHODS/DESIGN: The DASH after TBI study is an actively accruing, single-center, randomized, double-blinded, placebo-controlled, two-arm trial, where one group receives centrally acting sympatholytic drugs, propranolol (1 mg intravenously every 6 h for 7 days) and clonidine (0.1 mg per tube every 12 h for 7 days), and the other group, double placebo, within 48 h of severe TBI. The study uses a weighted adaptive minimization randomization with categories of age and Marshall head CT classification. Feasibility will be assessed by ability to provide a neuroradiology read for randomization, by treatment contamination, and by treatment compliance. The primary endpoint is reduction in plasma norepinephrine level as measured on day 8. Secondary endpoints include comprehensive plasma and urine catecholamine levels, heart rate variability, arrhythmia occurrence, infections, agitation measures using the Richmond Agitation-Sedation Scale and Agitated Behavior scale, medication use (anti-hypertensive, sedative, analgesic, and antipsychotic), coma-free days, ventilator-free days, length of stay, and mortality. Neuropsychological outcomes will be measured at hospital discharge and at 3 and 12 months. The domains tested will include global executive function, memory, processing speed, visual-spatial, and behavior. Other assessments include the Extended Glasgow Outcome Scale and Quality of Life after Brain Injury scale. Safety parameters evaluated will include cardiac complications. DISCUSSION: The DASH After TBI Study is the first randomized, double-blinded, placebo-controlled trial powered to determine feasibility and investigate safety and outcomes associated with adrenergic blockade in patients with severe TBI. If the study results in positive trends, this could provide pilot evidence for a larger multicenter randomized clinical trial. If there is no effect of therapy, this trial would still provide a robust prospective description of sympathetic hyperactivity after TBI. TRIAL REGISTRATION: ClinicalTrials.gov NCT0132204

Identifying temporal patterns in trauma admissions: Informing resource allocation.

BackgroundIncreased knowledge of the temporal patterns in the distribution of trauma admissions could be beneficial to staffing and resource allocation efforts. However, little work has been done to understand how this distribution varies based on patient acuity, trauma mechanism or need for intervention. We hypothesize that temporal patterns exist in the distribution of trauma admissions, and that deep patterns exist when traumas are analyzed by their type and severity.Study designWe conducted a cross-sectional observational study of adult patient flow at a level one trauma center over three years, 7/1/2013-6/30/2016. Primary thermal injuries were excluded. Frequency analysis was performed for patients grouped by ED disposition and mechanism against timing of admission; in subgroup analysis additional exclusion criteria were imposed.Results10,684 trauma contacts were analyzed. Trauma contacts were more frequent on Saturdays and Sundays than on weekdays (p<0.001). Peak arrival time was centered around evening shift change (6-7pm), but differed based on ED disposition: OR and ICU or Step-Down admissions (p = 0.0007), OR and floor admissions (p<0.0001), and ICU or Step-Down and floor admissions (p<0.0001). Step-Down and ICU arrival times (p = 0.42) were not different. Penetrating injuries peaked later than blunt (p<0.0001). Trauma varies throughout the year; we establish a high incidence trauma season (April to late October). Different mechanisms have varying dependence upon season; Motorcycle crashes (MCCs) have the greatest dependence.ConclusionWe identify new patterns in the temporal and seasonal variation of trauma and of specific mechanisms of injury, including the novel findings that 1) penetrating trauma tends to present at later times than blunt, and 2) critically ill patients requiring an OR tend to present later than those who are less acute and require an ICU or Step-Down unit. These patients present later than those who are admitted to the floor. Penetrating trauma patients arriving later than blunt may be the underlying reason why operative patients arrive later than other patients

Identifying temporal patterns in trauma admissions: Informing resource allocation.

BackgroundIncreased knowledge of the temporal patterns in the distribution of trauma admissions could be beneficial to staffing and resource allocation efforts. However, little work has been done to understand how this distribution varies based on patient acuity, trauma mechanism or need for intervention. We hypothesize that temporal patterns exist in the distribution of trauma admissions, and that deep patterns exist when traumas are analyzed by their type and severity.Study designWe conducted a cross-sectional observational study of adult patient flow at a level one trauma center over three years, 7/1/2013-6/30/2016. Primary thermal injuries were excluded. Frequency analysis was performed for patients grouped by ED disposition and mechanism against timing of admission; in subgroup analysis additional exclusion criteria were imposed.Results10,684 trauma contacts were analyzed. Trauma contacts were more frequent on Saturdays and Sundays than on weekdays (pConclusionWe identify new patterns in the temporal and seasonal variation of trauma and of specific mechanisms of injury, including the novel findings that 1) penetrating trauma tends to present at later times than blunt, and 2) critically ill patients requiring an OR tend to present later than those who are less acute and require an ICU or Step-Down unit. These patients present later than those who are admitted to the floor. Penetrating trauma patients arriving later than blunt may be the underlying reason why operative patients arrive later than other patients

The Value of Simplicity: Externally Validating the Baylor Cranial Gunshot Wound Prognosis Score

OBJECTIVE: Gunshot wounds to the head (GSWH) are devastating injuries with a grim prognosis. Several prognostic scores have been created to estimate mortality and functional outcome, including the so-called Baylor score, an uncomplicated scoring method based on bullet trajectory, patient age, and neurological status on admission. This study aimed to validate the Baylor score within a temporally, institutionally, and geographically distinct patient population. METHODS: Data were obtained from the trauma registry at a level I trauma center in the southeastern US. Patients with a GSWH in which dural penetration occurred were identified from data collected between January 1, 2009, and June 30, 2019. Patient demographics, medical history, bullet trajectory, intent of GSWH (e.g., suicide), admission vital signs, Glasgow Coma Scale score, pupillary response, laboratory studies, and imaging reports were collected. The Baylor score was calculated directly by using its clinical components. The ability of the Baylor score to predict mortality and good functional outcome (Glasgow Outcome Scale score 4 or 5) was assessed using the receiver operating characteristic curve and the area under the curve (AUC) as a measure of performance. RESULTS: A total of 297 patients met inclusion criteria (mean age 38.0 [SD 15.7] years, 73.4% White, 85.2% male). A total of 205 (69.0%) patients died, whereas 69 (23.2%) patients had good functional outcome. Overall, the Baylor score showed excellent discrimination of mortality (AUC = 0.88) and good functional outcome (AUC = 0.90). Baylor scores of 3-5 underestimated mortality. Baylor scores of 0, 1, and 2 underestimated good functional outcome. CONCLUSIONS: The Baylor score is an accurate and easy-to-use prognostic scoring tool that demonstrated relatively stable performance in a distinct cohort between 2009 and 2019. In the current era of trauma management, providers may continue to use the score at the point of admission to guide family counseling and to direct investment of healthcare resources

Limitations of Available Blood Products for Massive Transfusion During Mass Casualty Events at US Level 1 Trauma Centers

Introduction: Exsanguination remains a leading cause of preventable death in traumatically injured patients. To better treat hemorrhagic shock, hospitals have adopted massive transfusion protocols (MTPs) which accelerate the delivery of blood products to patients. There has been an increase in mass casualty events (MCE) worldwide over the past two decades. These events can overwhelm a responding hospitals supply of blood products. Using a computerized model, this study investigated the ability of US trauma centers (TCs) to meet the blood product requirements of MCEs. Methods: Cross-sectional survey data of on-hand blood products were collected from 16 US level-1 TCs. A discrete event simulation model of a TC was developed based on historic data of blood product consumption during MCEs. Each hospitals blood bank was evaluated across increasingly more demanding MCEs using modern MTPs to guide resuscitation efforts in massive transfusion (MT) patients. Results: A total of 9,000 simulations were performed on each TCs data. Under the least demanding MCE scenario, the median size MCE in which TCs failed to adequately meet blood product demand was 50 patients (IQR 20-90), considering platelets. Ten TCs exhaust their supply of platelets prior to red blood cells (RBCs) or plasma. Disregarding platelets, five TCs exhausted their supply of O- packed RBCs, six exhausted their AB plasma supply, and five had a mixed exhaustion picture. Conclusion: Assuming a TCs ability to treat patients is limited only by their supply of blood products, US level-1 TCs lack the on-hand blood products required to adequately treat patients following a MCE. Use of non-traditional blood products, which have a longer shelf life, may allow TCs to better meet the blood product requirement needs of patients following larger MCEs.Funding Agencies|Center for Translational Injury Research; John B Holmes Professorship in Clinical Sciences</p