Megan Y. Harada

Association Between Enoxaparin Dosage Adjusted by Anti-Factor Xa Trough Level and Clinically Evident Venous Thromboembolism After Trauma.

Importance Trauma patients are at high risk for developing venous thromboembolism (VTE). The VTE rate when enoxaparin sodium is dosed by anti-factor Xa (anti-Xa) trough level is not well described. Objective To determine whether targeting a prophylactic anti-Xa trough level by adjusting the enoxaparin dose would reduce the VTE rate in trauma patients. Design, Setting, and Participants Single-institution, historic vs prospective cohort comparison study at an urban, academic, level I trauma center. The prospective cohort was enrolled from August 2014 to May 2015 and compared with a historic cohort admitted from August 2013 to May 2014. Trauma patients who received enoxaparin adjusted by anti-Xa trough level (adjustment group) were compared with those who received enoxaparin sodium at a dosage of 30 mg twice daily (control group). Patients were excluded if they were younger than 18 years, had a length of hospital stay less than 2 days, or had preexisting deep vein thrombosis. Patients were excluded from the adjustment group for changes in the choice of thromboprophylaxis (heparin, enoxaparin once-daily dosing, early ambulation), hospital discharge before initial trough levels could be drawn, or incorrect timing of trough levels. Exposures Anti-Xa trough levels were monitored in patients in the adjustment group receiving 3 or more consecutive doses of enoxaparin sodium, 30 mg twice daily. Patients with a trough level of 0.1 IU/mL or lower received enoxaparin sodium increased by 10-mg increments. After providing 3 adjusted doses of enoxaparin, the trough level was redrawn and the dosage was adjusted as necessary. Patients in the control group received enoxaparin sodium at a dosage of 30 mg twice daily without adjustments. Main Outcomes and Measures Rates of symptomatic VTE (deep vein thrombosis and pulmonary embolism, confirmed by duplex ultrasonography and chest computed tomographic angiography, respectively) and bleeding risk. Results A total of 205 patients (mean [SD] age, 41.3 [18.2] years; 75.1% male) were studied, 87 in the adjustment group and 118 in the control group, with similar baseline characteristics and injury profiles. Subprophylactic anti-Xa troughs were noted in 73 of 87 patients (83.9%) in the adjustment group, and the majority of patients (57 of 87 patients [65.5%]) required dosage adjustment of enoxaparin sodium to 40 mg twice daily. Incidence of VTE was significantly lower in the adjustment group than in the control group (1.1% vs 7.6%, respectively; P = .046). When the adjustment group was compared with the control group, no significant difference was noted in the rate of packed red blood cell transfusion (6.9% vs 12.7%, respectively; P = .18) or mean (SD) hematocrit at discharge (34.5% [6.3%] vs 33.4% [6.8%], respectively [to convert to proportion of 1.0, multiply by 0.01]; P = .19). Conclusions and Relevance In this study, subprophylactic anti-Xa trough levels were common in trauma patients. Enoxaparin dosage adjustment may lead to a reduced rate of VTE without an increased risk of bleeding.

Early propranolol after traumatic brain injury is associated with lower mortality.

BACKGROUND &bgr;-Adrenergic receptor blockers (BBs) administered after trauma blunt the cascade of immune and inflammatory changes associated with injury. BBs are associated with improved outcomes after traumatic brain injury (TBI). Propranolol may be an ideal BB because of its nonselective inhibition and ability to cross the blood-brain barrier. We determined if early administration of propranolol after TBI is associated with lower mortality. METHODS All adults (age ≥ 18 years) with moderate-to-severe TBI (head Abbreviated Injury Scale [AIS] score, 3–5) requiring intensive care unit (ICU) admission at a Level I trauma center from January 1, 2013, to May 31, 2015, were prospectively entered into a database. Administration of early propranolol was dosed within 24 hours of admission at 1 mg intravenous every 6 hours. Patients who received early propranolol after TBI (EPAT) were compared with those who did not (non-EPAT). Data including demographics, hospital length of stay (LOS), ICU LOS, and mortality were collected. RESULTS Over 29 months, 440 patients with moderate-to-severe TBI met inclusion criteria. Early propranolol was administered to 25% (109 of 440) of the patients. The EPAT cohort was younger (49.6 years vs. 60.4 years, p < 0.001), had lower Glasgow Coma Scale (GCS) score (11.7 vs. 12.4, p = 0.003), had lower head AIS score (3.6 vs. 3.9, p = 0.001), had higher admission heart rate (95.8 beats/min vs. 88.4 beats/min, p = 0.002), and required more days on the ventilator (5.9 days vs. 2.6 days, p < 0.001). Similarities were noted in sex, Injury Severity Score (ISS), admission systolic blood pressure, hospital LOS, ICU LOS, and mortality rate. Multivariate regression showed that EPAT was independently associated with lower mortality (adjusted odds ratio, 0.25; p = 0.012). CONCLUSION After adjusting for predictors of mortality, early administration of propranolol after TBI was associated with improved survival. Future studies are needed to identify additional benefits and optimal dosing regimens. LEVEL OF EVIDENCE Therapeutic study, level IV.

Field intubation in civilian patients with hemorrhagic shock is associated with higher mortality.

BACKGROUND Field intubation (FI) by emergency medical service personnel on severely injured trauma patients remains a contentious practice. Clinical studies suggest an association between FI and adverse outcomes in patients with traumatic brain injury. Military tactical emergency casualty care recommends deferring intubation and providing supplemental oxygenation until reaching a more equipped destination. In addition, animal models with penetrating hemorrhagic shock demonstrate increased acidosis with intubation before resuscitation. The purpose of this study was to evaluate the impact of FI on outcomes in trauma patients with hemorrhagic shock requiring massive transfusion. METHODS The Los Angeles County Trauma System Database was retrospectively queried for all trauma patients 16 years or older with hemorrhagic shock requiring massive transfusion (≥6 U packed red blood cells in the first 24 hours) between January 1, 2012, and June 30, 2014. Demographics, clinical and transfusion data, and outcomes were compared between patients who received FI and those who did not (NO-FI). Multivariate regression analysis was used to adjust for confounders. RESULTS Of 552 trauma patients meeting inclusion criteria, 63 (11%) received FI, and the remaining 489 (89%) were NO-FI. Age, sex, and incidence of blunt injury were similar between the FI and the NO-FI group. The FI cohort presented with a lower median Glasgow Coma Scale (GCS) score (3 vs. 14, p < 0.001), a lower median systolic blood pressure (86 mm Hg vs. 104 mm Hg, p < 0.001), and a higher median Injury Severity Score (ISS) (41 vs. 29, p < 0.001). Mortality was significantly higher in FI patients (83% vs. 43%, p < 0.001). Transfusion patterns and total field times were similar in both groups. After adjusting for confounders, FI patients had increased odds of mortality (adjusted odds ratio, 2.89; 95% confidence interval, 1.08–7.78; p = 0.035). In addition, FI was identified as an independent predictor of mortality (adjusted odds ratio, 3.41; 95% confidence interval, 1.35–8.59; p = 0.009). CONCLUSION FI may be associated with higher mortality in trauma patients with hemorrhagic shock requiring massive transfusion. Less invasive airway interventions and rapid transport might improve outcomes for these patients. LEVEL OF EVIDENCE Therapeutic study, level IV; epidemiologic study, level III.

A model of recurrent concussion that leads to long-term motor deficits, CTE-like tauopathy and exacerbation of an ALS phenotype.

BACKGROUND Concussion injury is the most common form of traumatic brain injury (TBI). How recurrent concussions alter long-term outcomes is poorly understood, especially as related to the development of neurodegenerative disease. We evaluated the functional and pathological consequences of repeated TBI over time in wild type (WT) rats as well as rats harboring the human SOD1G93A mutation (“SOD1”), a model of familial amyotrophic lateral sclerosis (ALS). METHODS A total of 42 rats, 26 WT and 16 SOD1, were examined over a study period of 25 weeks (or endpoint). At postnatal day 60, 20 WT and 7 SOD1 rats were exposed to mild, bilateral TBI once per week for either 2 weeks (2×TBI) or 5 weeks (5×TBI) using a controlled cortical impact device. Six WT and nine SOD1 rats underwent sham injury with anesthesia alone. Twenty WT rats were euthanized at 12 weeks after first injury and six WT rats were euthanized at 25 weeks after first injury. SOD1 rats were euthanized when they reached ALS disease endpoint. Weekly body weights and behavioral assessments were performed. Tauopathy in brain tissue was analyzed using immunohistochemistry. RESULTS 2XTBI injured rats initially demonstrated recovery of motor function but failed to recover to baseline within the 12-week study period. Relative to both 2XTBI and sham controls, 5XTBI rats demonstrated significant deficits that persisted over the 12-week period. SOD1 5XTBI rats reached a peak body weight earlier than sham SOD1 rats, indicating earlier onset of the ALS phenotype. Histologic examination of brain tissue revealed that, in contrast with sham controls, SOD1 and WT TBI rats demonstrated cortical and corpus collosum thinning and tauopathy, which increased over time. CONCLUSIONS Unlike previous models of repeat brain injury, which demonstrate only transient deficits in motor function, our concussion model of repeat, mild, bilateral TBI induced long-lasting deficits in motor function, decreased cortical thickness, shrinkage of the corpus callosum, increased brain tauopathy, and earlier onset of ALS symptoms in SOD1 rats. This model may allow for a greater understanding of the complex relationship between TBI and neurodegenerative diseases and provides a potential method for testing novel therapeutic strategies.

Bicycle trauma and alcohol intoxication

INTRODUCTION As bicycling has become more popular, admissions after bicycle trauma are on the rise. The impact of alcohol use on bicycle trauma has not been well studied. The aim of this study was to examine the effect of alcohol intoxication on injury burden following bicycle-related crashes. METHODS A retrospective review of trauma patients presenting to a Level I trauma center after bicycle-related crashes from January 2002 to December 2011 was conducted. Demographics, injury data, alcohol intoxication, helmet use, and clinical outcomes were reviewed. Blood alcohol level (BAL) was considered positive if >0.01 g/dL. Variables were compared between patients based on BAL: negative, 0.01-0.16 g/dL, and >0.16 g/dL. RESULTS During the 10 year study period, 563 patients met study criteria; mean age was 33.5 ± 16.5 years, 87% were male, and mortality was 1%. On average, bicycle crashes increased over the study period by 4.4 collisions per year. BAL was tested in 211 (38%) patients. Mean BAL was 0.24 g/dL, with 37% of these patients being intoxicated (BAL ≥ 0.010 g/dL). Intoxicated patients were significantly less likely to wear a helmet (4.7% vs. 22.2%, p = 0.002) and to be involved in motor vehicle crash (59.0% vs. 81.2%, p < 0.001). There was no difference noted in the injury burden including ISS ≥ 16 (14.3% vs. 19.5%, p = 0.335) and AIS Head ≥ 3 (17.9% vs. 21.8%, p = 0.502). When comparing patients according to their BAL, there was a decreasing risk of motor vehicle collision with increasing BAL (81.2% for undetected, 76.5% for BAL ≤ 0.16 g/dL and 54.1% for BAL >0.16 g/dL, p < 0.001). The risk for a severe head injury (AIS Head ≥ 3) was significantly lower in helmeted patients (8.4% vs. 15.8%, p = 0.035). CONCLUSIONS The incidence of bicycle-related crashes is increasing and more than a third of patients tested for alcohol after bicycle-related crashes are found to be intoxicated. The injury burden in intoxicated patients, including head trauma, was not different compared to non-intoxicated patients. In addition, the risk for a collision with a motor vehicle was significantly lower. Nonetheless, these patients rarely utilize a helmet. The findings from this study can be used for the development and implementation of preventive strategies to minimize the injury burden associated with bicycle crashes and intoxicated cyclists.

Overtreatment of Heparin-Induced Thrombocytopenia in the Surgical ICU.

Objective: Recent studies reveal a high occurrence of overdiagnosis of heparin-induced thrombocytopenia in surgical patients with critical illness. The optimal criteria for diagnosis of heparin-induced thrombocytopenia remain unclear, contributing to unnecessary treatment. We reviewed patients who were admitted to surgical ICUs and were suspected of heparin-induced thrombocytopenia to identify how often patients were correctly treated. Design: In this clinical prospective study, data were collected including age, sex, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, serotonin release assay, and Warkentin 4Ts scores. Heparin-induced thrombocytopenia-positive patients were defined as those with both positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay (optical density, ≥ 0.40) and positive serotonin release assay results. Setting: Urban tertiary medical center. Patients: Patients admitted to the surgical and cardiac ICU who were presumed to have heparin-induced thrombocytopenia and underwent antiplatelet factor 4/heparin enzyme-linked immunosorbent assay and serotonin release assay testing between January 1, 2011, and August 1, 2014. Interventions: None. Measurements and Main Results: A total of 135 patients had 4Ts, antiplatelet factor 4/heparin enzyme-linked immunosorbent assay, and serotonin release assay scores. A total of 11 patients (8.1%) had positive serotonin release assay and 80 patients had positive antiplatelet factor 4/heparin enzyme-linked immunosorbent assay; 10 patients were identified as heparin-induced thrombocytopenia positive. Positive serotonin release assay was noted in nine of 11 patients (81.8%) with antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density greater than or equal to 2.0, compared with one of 22 patients (4.5%) with optical density values of 0.85–1.99, and one of 102 patients (1.0%) with optical density values of 0–0.84. Out of 135 patients, 29 patients (21.5%) received treatment with argatroban, lepirudin, or fondaparinux: 10 of 10 heparin-induced thrombocytopenia-positive patients (100%) compared with 19 of 125 heparin-induced thrombocytopenia-negative patients (15%). Conclusions: Overtreatment of heparin-induced thrombocytopenia in the surgical ICU continues even with recent increased caution encouraging a higher antiplatelet factor 4/heparin enzyme-linked immunosorbent assay optical density threshold before initiating treatment. More stringent criteria should be used to determine when to order serologic testing and when the results of such testing should prompt a change in anticoagulant treatment. If antiplatelet factor 4/heparin enzyme-linked immunosorbent assay is used to consider immediate treatment, an optical density greater than or equal to 2.0 may be a more appropriate threshold.

Predictors of improved functional outcome following inpatient rehabilitation for patients with traumatic brain injury

OBJECTIVE To determine factors associated with response to inpatient rehabilitation treatment among TBI patients. SETTING Inpatient rehabilitation service at a Level I trauma center. PARTICIPANTS Moderate-severe TBI patients ages ≥ 18years old admitted between January 1, 2002 and December 31, 2012. MAIN MEASURES Response to inpatient rehabilitation, measured by the Functional Independence Measure (FIM) score. DESIGN Retrospective cohort study. RESULTS Of 1,984 patients treated for TBI, 184 (10.8%) underwent inpatient rehabilitation. The largest proportion of patients improved in mobility (98.9%), followed by self-care (93.7%), communication/social cognition (84.0%), and sphincter control (65.7%). Of these, 99 (53.8%) improved by 2 or more levels of functional independence and were considered rehabilitation responders. Responders were younger (53.1 years vs. 63.8, p < 0.01), had longer average rehabilitation stays (15.4 days vs. 12.2, p < 0.01), and were less likely to have an admission SBP <100 mmHg (7.1% vs. 17.1%, p = 0.01). On multivariate analysis, normotension at admission (AOR 0.06, p = 0.01) and longer rehabilitation LOS (AOR 1.11, p < 0.01) were associated with a response to inpatient rehabilitation. CONCLUSION Of the TBI patients who qualified for same-center inpatient rehabilitation, approximately half responded to treatment. Longer rehabilitation time and normotension at admission predicted response to rehabilitation. Further efforts are necessary to identify and optimize TBI patients for inpatient rehabilitation.

Clinical correlates to assist with chronic traumatic encephalopathy diagnosis: Insights from a novel rodent repeat concussion model

INTRODUCTION Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease linked to repetitive head injuries. Chronic traumatic encephalopathy symptoms include changes in mood, behavior, cognition, and motor function; however, CTE is currently diagnosed only postmortem. Using a rat model of recurrent traumatic brain injury (TBI), we demonstrate rodent deficits that predict the severity of CTE-like brain pathology. METHODS Bilateral, closed-skull, mild TBI was administered once per week to 35 wild-type rats; eight rats received two injuries (2×TBI), 27 rats received five injuries (5×TBI), and 13 rats were sham controls. To determine clinical correlates for CTE diagnosis, TBI rats were separated based on the severity of rotarod deficits and classified as “mild” or “severe” and further separated into “acute,” “short,” and “long” based on age at euthanasia (90, 144, and 235 days, respectively). Brain atrophy, phosphorylated tau, and inflammation were assessed. RESULTS All eight 2×TBI cases had mild rotarod deficiency, 11 5×TBI cases had mild deficiency, and 16 cases had severe deficiency. In one cohort of rats, tested at approximately 235 days of age, balance, rearing, and grip strength were significantly worse in the severe group relative to both sham and mild groups. At the acute time period, cortical thinning, phosphorylated tau, and inflammation were not observed in either TBI group, whereas corpus callosum thinning was observed in both TBI groups. At later time points, atrophy, tau pathology, and inflammation were increased in mild and severe TBI groups in the cortex and corpus callosum, relative to sham controls. These injury effects were exacerbated over time in the severe TBI group in the corpus callosum. CONCLUSIONS Our model of repeat mild TBI suggests that permanent deficits in specific motor function tests correlate with CTE-like brain pathology. Assessing balance and motor coordination over time may predict CTE diagnosis.

Decreased transport time to the surgical intensive care unit

INTRODUCTION Extended stay in the emergency department (ED) is associated with worse outcomes in critically ill trauma patients. We conducted a human factors analysis to better understand impediments for patient flow when a surgical ICU (SICU bed is available in order to reduce ED LOS. METHODS This is a retrospective review of all trauma patients admitted to a protected SICU through the ED during 2011 and 2014. In 2010, a 24-hour protected SICU bed protocol was implemented to make a bed readily available. During 2013 human factors analysis helped to describe flow disruptions; related interventions were introduced to facilitate rapid transport from the ED to SICU. The interventions required the following prior to CT scanning: immediate ICU bed orders placed by the ED physician and ED to ICU personnel communication. Direct transport from the CT scanner to the ICU was mandated. Data including patient demographics, injury severity, ED LOS, ICU LOS, and hospital LOS was collected and compared between 2011 (PRE) and 2014 (POST). RESULTS A total of 305 trauma patients admitted from the ED to the SICU were analyzed; 174 patients in 2011 (PRE) and 131 in 2014 (POST). Average age was 46 years and patients had a mean admission GCS and injury severity score (ISS) of 12.3 and 15.9, respectively. The cohorts were similar in age, mechanism of injury, initial vital signs, and injury severity. After implementing the human factors interventions, decreases were noted in the mean ED LOS (2.4 v. 3.0 hours, p=0.005) and ICU LOS (4.0 v. 4.8 days, p=0.023). No differences in hospital LOS or mortality were observed. CONCLUSIONS While an open SICU bed protocol may facilitate rapid transport of trauma patients from the ED to the ICU, additional human factors interventions emphasizing improved communication and coordination can further reduce time spent in the ED. LEVEL OF EVIDENCE Level IV, Economic/Decision.

Heart rate in pediatric trauma: rethink your strategy

BACKGROUND The optimal heart rate (HR) for children after trauma is based on values derived at rest for a given age. As the stages of shock are based in part on HR, a better understanding of how HR varies after trauma is necessary. Admission HRs of pediatric trauma patients were analyzed to determine which ranges were associated with lowest mortality. MATERIALS AND METHODS The National Trauma Data Bank was used to evaluate all injured patients ages 1-14 years admitted between 2007 and 2011. Patients were stratified into eight groups based on age. Clinical characteristics and outcomes were recorded, and regression analysis was used to determine mortality odds ratios (ORs) for HR ranges within each age group. RESULTS A total of 214,254 pediatric trauma patients met inclusion criteria. The average admission HR and systolic blood pressure were 104.7 and 120.4, respectively. Overall mortality was 0.8%. The HR range associated with lowest mortality varied across age groups and, in children ages 7-14, was narrower than accepted resting HR ranges. The lowest risk of mortality for patients ages 5-14 was captured at HR 80-99. CONCLUSIONS The HR associated with lowest mortality after pediatric trauma frequently differs from resting HR. Our data suggest that a 7y old with an HR of 115 bpm may be in stage III shock, whereas traditional HR ranges suggest that this is a normal rate for this child. Knowing when HR is critically high or low in the pediatric trauma population will better guide treatment.