Effect of Out-of-Hospital Tranexamic Acid vs Placebo on 6-Month Functional Neurologic Outcomes in Patients With Moderate or Severe Traumatic Brain Injury.

Importance: Traumatic brain injury (TBI) is the leading cause of death and disability due to trauma. Early administration of tranexamic acid may benefit patients with TBI. Objective: To determine whether tranexamic acid treatment initiated in the out-of-hospital setting within 2 hours of injury improves neurologic outcome in patients with moderate or severe TBI. Design, Setting, and Participants: Multicenter, double-blinded, randomized clinical trial at 20 trauma centers and 39 emergency medical services agencies in the US and Canada from May 2015 to November 2017. Eligible participants (N = 1280) included out-of-hospital patients with TBI aged 15 years or older with Glasgow Coma Scale score of 12 or less and systolic blood pressure of 90 mm Hg or higher. Interventions: Three interventions were evaluated, with treatment initiated within 2 hours of TBI: out-of-hospital tranexamic acid (1 g) bolus and in-hospital tranexamic acid (1 g) 8-hour infusion (bolus maintenance group; n = 312), out-of-hospital tranexamic acid (2 g) bolus and in-hospital placebo 8-hour infusion (bolus only group; n = 345), and out-of-hospital placebo bolus and in-hospital placebo 8-hour infusion (placebo group; n = 309). Main Outcomes and Measures: The primary outcome was favorable neurologic function at 6 months (Glasgow Outcome Scale-Extended score >4 [moderate disability or good recovery]) in the combined tranexamic acid group vs the placebo group. Asymmetric significance thresholds were set at 0.1 for benefit and 0.025 for harm. There were 18 secondary end points, of which 5 are reported in this article: 28-day mortality, 6-month Disability Rating Scale score (range, 0 [no disability] to 30 [death]), progression of intracranial hemorrhage, incidence of seizures, and incidence of thromboembolic events. Results: Among 1063 participants, a study drug was not administered to 96 randomized participants and 1 participant was excluded, resulting in 966 participants in the analysis population (mean age, 42 years; 255 [74%] male participants; mean Glasgow Coma Scale score, 8). Of these participants, 819 (84.8%) were available for primary outcome analysis at 6-month follow-up. The primary outcome occurred in 65% of patients in the tranexamic acid groups vs 62% in the placebo group (difference, 3.5%; [90% 1-sided confidence limit for benefit, -0.9%]; P = .16; [97.5% 1-sided confidence limit for harm, 10.2%]; P = .84). There was no statistically significant difference in 28-day mortality between the tranexamic acid groups vs the placebo group (14% vs 17%; difference, -2.9% [95% CI, -7.9% to 2.1%]; P = .26), 6-month Disability Rating Scale score (6.8 vs 7.6; difference, -0.9 [95% CI, -2.5 to 0.7]; P = .29), or progression of intracranial hemorrhage (16% vs 20%; difference, -5.4% [95% CI, -12.8% to 2.1%]; P = .16). Conclusions and Relevance: Among patients with moderate to severe TBI, out-of-hospital tranexamic acid administration within 2 hours of injury compared with placebo did not significantly improve 6-month neurologic outcome as measured by the Glasgow Outcome Scale-Extended. Trial Registration: ClinicalTrials.gov Identifier: NCT01990768.

Use of whole body CT to detect patterns of CPR-related injuries after sudden cardiac arrest.

AIMS AND OBJECTIVES: We have recently implemented a dedicated sudden cardiac arrest (SCA) - whole-body computed tomography (WBCT) protocol to evaluate SCA patients with return of spontaneous circulation (ROSC) following cardiopulmonary resuscitation (CPR). The aim of this study is to evaluate the number and pattern of CPR-related injuries in ROSC patients with SCA-WBCT. METHODS AND MATERIALS: Single-centre retrospective review of 39 patients (13 female; 20 male, mean age 51.8 years) with non-traumatic, out-of-hospital SCA and ROSC and evaluation with dedicated SCA-WBCT over a 10-month period. RESULTS: In-hospital mortality was 54%. CPR-related injuries were detected in 85% (33/39). Chest injuries were most common on WBCT: 85% (33) subjects had rib fractures (mean of 8.5 fractures/subject); 31% (12) sternal fractures; 13% (5) mediastinal haematoma; 10% (4) pneumothorax; 8% (3) pneumomediastinum and 3% (1) haemothorax. Three subjects (8%) had abdominal injuries on WBCT, including one hepatic haematoma with active haemorrhage. CONCLUSION: CPR-related injuries on WBCT after ROSC are common, with serial rib fractures detected most commonly. An unexpectedly high rate of abdominal injuries was detected on SCA-WBCT. Radiologists need to be attuned to the spectrum of CPR-related injuries in WBCT, including abdominal injuries and subtle rib fractures. KEY POINTS: • CPR frequently causes injuries. • Radiologists should be aware of the spectrum of CPR related injuries. • Rib fractures are frequent and radiologic findings often subtle. • Clinically unexpected abdominal injuries may be present.

Accuracy of outside radiologists' reports of computed tomography exams of emergently transferred patients.

PURPOSE: Growing numbers of patient with advanced imaging being transferred to trauma centers has resulted in increased numbers of outside CT scans received at trauma centers. This study examines the degree of agreement between community radiologists' interpretations of the CT scans of transferred patients and trauma center radiologists' reinterpretation. METHODS: All CT scans of emergency transfer patients received over a 1 month period were reviewed by an emergency radiologist. Patients were classified as trauma or non-trauma and exams as neuro or non-neuro. Interpretive discrepancies between the emergency radiologist and community radiologist were classified as minor, moderate, or major. Major discrepancies were confirmed by review of a second emergency radiologist. Discrepancy rates were calculated on a per-patient and per exam basis. RESULTS: Six hundred twenty-seven CT scans of 326 patients were reviewed. Major discrepancies were encountered in 52 (16.0%, 95% CI 12.2-20.5) patients and 53 exams (8.5%, 95% CI 6.5-10.5). These were discovered in 46 trauma patients (21.6%, 95% CI 16.4-27.9) compared to six non-trauma patients (5.3%, 95% CI 2.2-11.7) (P < 0.001). A significant difference in the major discrepancy rate was also found between non-neuro and neuro exams (12.4 vs 3.3%, respectively, P < 0.001), primarily due to discrepancies in trauma patients, rather than non-trauma patients. CONCLUSIONS: Potentially management-changing interpretive changes affected 16% of transferred patients and 8.5% of CT exams over a 1 month period. Trauma center reinterpretations of community hospital CT scans of transferred patients provide valuable additional information to the clinical services caring for critically ill patients.

Chest compression rates and survival following out-of-hospital cardiac arrest.

OBJECTIVE: Guidelines for cardiopulmonary resuscitation recommend a chest compression rate of at least 100 compressions/min. A recent clinical study reported optimal return of spontaneous circulation with rates between 100 and 120/min during cardiopulmonary resuscitation for out-of-hospital cardiac arrest. However, the relationship between compression rate and survival is still undetermined. DESIGN: Prospective, observational study. SETTING: Data is from the Resuscitation Outcomes Consortium Prehospital Resuscitation IMpedance threshold device and Early versus Delayed analysis clinical trial. PARTICIPANTS: Adults with out-of-hospital cardiac arrest treated by emergency medical service providers. INTERVENTIONS: None. MEASUREMENTS MAIN RESULTS: Data were abstracted from monitor-defibrillator recordings for the first five minutes of emergency medical service cardiopulmonary resuscitation. Multiple logistic regression assessed odds ratio for survival by compression rate categories (<80, 80-99, 100-119, 120-139, ≥140), both unadjusted and adjusted for sex, age, witnessed status, attempted bystander cardiopulmonary resuscitation, location of arrest, chest compression fraction and depth, first rhythm, and study site. Compression rate data were available for 10,371 patients; 6,399 also had chest compression fraction and depth data. Age (mean±SD) was 67±16 years. Chest compression rate was 111±19 per minute, compression fraction was 0.70±0.17, and compression depth was 42±12 mm. Circulation was restored in 34%; 9% survived to hospital discharge. After adjustment for covariates without chest compression depth and fraction (n=10,371), a global test found no significant relationship between compression rate and survival (p=0.19). However, after adjustment for covariates including chest compression depth and fraction (n=6,399), the global test found a significant relationship between compression rate and survival (p=0.02), with the reference group (100-119 compressions/min) having the greatest likelihood for survival. CONCLUSIONS: After adjustment for chest compression fraction and depth, compression rates between 100 and 120 per minute were associated with greatest survival to hospital discharge.

Revisiting the "Golden Hour": An Evaluation of Out-of-Hospital Time in Shock and Traumatic Brain Injury.

STUDY OBJECTIVE: We evaluate patients with shock and traumatic brain injury who were previously enrolled in an out-of-hospital clinical trial to test the association between out-of-hospital time and outcome. METHODS: This was a secondary analysis of patients with shock and traumatic brain injury who were aged 15 years or older and enrolled in a Resuscitation Outcomes Consortium out-of-hospital clinical trial by 81 emergency medical services agencies transporting to 46 Level I and II trauma centers in 11 sites (May 2006 through May 2009). Inclusion criteria were systolic blood pressure less than or equal to 70 mm Hg or systolic blood pressure 71 to 90 mm Hg with pulse rate greater than or equal to 108 beats/min (shock cohort) and Glasgow Coma Scale score less than or equal to 8 (traumatic brain injury cohort); patients meeting both criteria were placed in the shock cohort. Primary outcomes were 28-day mortality (shock cohort) and 6-month Glasgow Outcome Scale-Extended score less than or equal to 4 (traumatic brain injury cohort). RESULTS: There were 778 patients in the shock cohort (26% 28-day mortality) and 1,239 patients in the traumatic brain injury cohort (53% 6-month Glasgow Outcome Scale-Extended score ≤4). Out-of-hospital time greater than 60 minutes was not associated with worse outcomes after accounting for important confounders in the shock cohort (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.77 to 2.62) or traumatic brain injury cohort (aOR 0.77; 95% CI 0.51 to 1.15). However, shock patients requiring early critical hospital resources and arriving after 60 minutes had higher 28-day mortality (aOR 2.37; 95% CI 1.05 to 5.37); this finding was not observed among a similar traumatic brain injury subgroup. CONCLUSION: Among out-of-hospital trauma patients meeting physiologic criteria for shock and traumatic brain injury, there was no association between time and outcome. However, the subgroup of shock patients requiring early critical resources and arriving after 60 minutes had higher mortality.

The effects of prehospital TXA on mortality and neurologic outcomes in patients with traumatic intracranial hemorrhage: a subgroup analysis from the prehospital TXA for TBI trial.

BACKGROUND: In the Prehospital Tranexamic Acid (TXA) for TBI Trial, TXA administered within two hours of injury in the out-of-hospital setting did not reduce mortality in all patients with moderate/severe traumatic brain injury (TBI). We examined the association between TXA dosing arms, neurologic outcome, and mortality in patients with intracranial hemorrhage (ICH) on computed tomography (CT). METHODS: This was a secondary analysis of the Prehospital Tranexamic Acid for TBI Trial (ClinicalTrials.gov [NCT01990768]) that randomized adults with moderate/severe TBI (Glasgow Coma Scale<13) and systolic blood pressure > =90 mmHg within two hours of injury to a 2-gram out-of-hospital TXA bolus followed by an in-hospital saline infusion, a 1-gram out-of-hospital TXA bolus/1-gram in-hospital TXA infusion, or an out-of-hospital saline bolus/in-hospital saline infusion (placebo). This analysis included the subgroup with ICH on initial CT. Primary outcomes included 28-day mortality, 6-month Glasgow Outcome Scale-Extended (GOSE) < = 4, and 6-month Disability Rating Scale (DRS). Outcomes were modeled using linear regression with robust standard errors. RESULTS: The primary trial included 966 patients. Among 541 participants with ICH, 28-day mortality was lower in the 2-gram TXA bolus group (17%) compared to the other two groups (1-gram bolus/1-gram infusion 26%, placebo 27%). The estimated adjusted difference between the 2-gram bolus and placebo groups was -8·5 percentage points (95% CI, -15.9 to -1.0) and between the 2-gram bolus and 1-gram bolus/1-gram infusion groups was -10.2 percentage points (95% CI, -17.6 to -2.9). DRS at 6 months was lower in the 2-gram TXA bolus group than the 1-gram bolus/1-gram infusion (estimated difference -2.1 [95% CI, -4.2 to -0.02]) and placebo groups (-2.2 [95% CI, -4.3, -0.2]). Six-month GOSE did not differ among groups. CONCLUSIONS: A 2-gram out-of-hospital TXA bolus in patients with moderate/severe TBI and ICH resulted in lower 28-day mortality and lower 6-month DRS than placebo and standard TXA dosing. LEVEL OF EVIDENCE: Therapeutic/Care Management, Level II.

Muscle oxygenation as an indicator of shock severity in patients with suspected severe sepsis or septic shock.

PURPOSE: The aim of this pilot study was to evaluate the potential of a new noninvasive optical measurement of muscle oxygenation (MOx) to identify shock severity in patients with suspected sepsis. METHODS: We enrolled 51 adult patients in the emergency department (ED) who presented with possible sepsis using traditional Systematic Inflammatory Response Syndrome criteria or who triggered a "Code Sepsis." Noninvasive MOx measurements were made from the first dorsal interosseous muscles of the hand once potential sepsis/septic shock was identified, as soon as possible after admission to the ED. Shock severity was defined by concurrent systolic blood pressure, heart rate, and serum lactate levels. MOx was also measured in a control group of 17 healthy adults. RESULTS: Mean (± SD) MOx in the healthy control group was 91.0 ± 5.5% (n = 17). Patients with mild, moderate, and severe shock had mean MOx values of 79.4 ± 21.2%, 48.6 ± 28.6%, and 42.2 ± 4.7%, respectively. Mean MOx for the mild and moderate shock severity categories were statistically different from healthy controls and from each other based on two-sample t-tests (p < 0.05). CONCLUSIONS: We demonstrate that noninvasive measurement of MOx was associated with clinical assessment of shock severity in suspected severe sepsis or septic shock. The ability of MOx to detect even mild septic shock has meaningful implications for emergency care, where decisions about triage and therapy must be made quickly and accurately. Future longitudinal studies may validate these findings and the value of MOx in monitoring patient status as treatment is administered.

Muscle Oxygenation as an Early Predictor of Shock Severity in Trauma Patients.

INTRODUCTION: We evaluated the potential utility of a new prototype noninvasive muscle oxygenation (MOx) measurement for the identification of shock severity in a population of patients admitted to the trauma resuscitation rooms of a Level I regional trauma center. The goal of this project was to correlate MOx with shock severity as defined by standard measures of shock: systolic blood pressure, heart rate, and lactate. METHODS: Optical spectra were collected from subjects by placement of a custom-designed optical probe over the first dorsal interosseous muscles on the back of the hand. Spectra were acquired from trauma patients as soon as possible upon admission to the trauma resuscitation room. Patients with any injury were eligible for study. MOx was determined from the collected optical spectra with a multiwavelength analysis that used both visible and near-infrared regions of light. Shock severity was determined in each patient by a scoring system based on combined degrees of hypotension, tachycardia, and lactate. MOx values of patients in each shock severity group (mild, moderate, and severe) were compared using two-sample t tests. RESULTS: In 17 healthy control patients, the mean MOx value was 91.0 ±â€Š5.5%. A total of 69 trauma patients were studied. Patients classified as having mild shock had a mean MOx of 62.5 ±â€Š26.2% (n = 33), those classified as in moderate shock had a mean MOx of 56.9 ±â€Š26.9% (n = 25) and those classified as in severe shock had a MOx of 31.0 ±â€Š17.1% (n = 11). Mean MOx for each of these groups was statistically different from the healthy control group (P < 0.05).Receiver operating characteristic analyses show that MOx and shock index (heart rate/systolic blood pressure) identified shock similarly well (area under the curves [AUC] = 0.857 and 0.828, respectively). However, MOx identified mild shock better than shock index in the same group of patients (AUC = 0.782 and 0.671, respectively). CONCLUSIONS: The results obtained from this pilot study indicate that MOx correlates with shock severity in a population of trauma patients. Noninvasive and continuous MOx holds promise to aid in patient triage and to evaluate patient condition throughout the course of resuscitation.

A Geospatial Analysis of Severe Firearm Injuries Compared to Other Injury Mechanisms: Event Characteristics, Location, Timing, and Outcomes.

OBJECTIVES: Relatively little is known about the context and location of firearm injury events. Using a prospective cohort of trauma patients, we describe and compare severe firearm injury events to other violent and nonviolent injury mechanisms regarding incident location, proximity to home, time of day, spatial clustering, and outcomes. METHODS: This was a secondary analysis of a prospective cohort of injured children and adults with hypotension or Glasgow Coma Scale score ≤ 8, injured by one of four primary injury mechanisms (firearm, stabbing, assault, and motor vehicle collision [MVC]) who were transported by emergency medical services to a Level I or II trauma center in 10 regions of the United States and Canada from January 1, 2010, through June 30, 2011. We used descriptive statistics and geospatial analyses to compare the injury groups, distance from home, outcomes, and spatial clustering. RESULTS: There were 2,079 persons available for analysis, including 506 (24.3%) firearm injuries, 297 (14.3%) stabbings, 339 (16.3%) assaults, and 950 (45.7%) MVCs. Firearm injuries resulted in the highest proportion of serious injuries (66.3%), early critical resources (75.3%), and in-hospital mortality (53.5%). Injury events occurring within 1 mile of a patient's home included 53.9% of stabbings, 49.2% of firearm events, 41.3% of assaults, and 20.0% of MVCs; the non-MVC events frequently occurred at home. While there was geospatial clustering, 94.4% of firearm events occurred outside of geographic clusters. CONCLUSIONS: Severe firearm events tend to occur within a patient's own neighborhood, often at home, and generally outside of geospatial clusters. Public health efforts should focus on the home in all types of neighborhoods to reduce firearm violence.

Post-discharge outcomes after resuscitation from out-of-hospital cardiac arrest: A ROC PRIMED substudy.

IMPORTANCE: Assessment of morbidity is an important component of evaluating interventions for patients with out-of-hospital cardiac arrest (OHCA). OBJECTIVE: We evaluated among survivors of OHCA cognition, functional status, health-related quality of life and depression as functions of patient and emergency medical services (EMS) factors. DESIGN: Prospective cohort sub-study of a randomized trial. SETTING: The parent trial studied two comparisons in persons with non-traumatic OHCA treated by EMS personnel participating in the Resuscitation Outcomes Consortium. PARTICIPANTS: Consenting survivors to discharge. MAIN OUTCOME MEASURES: Telephone assessments up to 6 months after discharge included neurologic function (modified Rankin score, MRS), cognitive impairment (Adult Lifestyle and Function Mini Mental Status Examination, ALFI-MMSE), health-related quality of life (Health Utilities Index Mark 3, HUI3) and depression (Telephone Geriatric Depression Scale, T-GDS). RESULTS: Of 15,794 patients enrolled in the parent trial, 729 (56% of survivors) consented. About 644 respondents (88% of consented) completed ≥ 1 assessment. Likelihood of assessment was associated with baseline characteristics and study site. Most respondents had MRS ≤ 3 (82.7%), no cognitive impairment (82.7% ALFI-MMSE ≥ 17), no severe impairment in health (71.6%, HUI3 ≥ 0.7) and no depression (90.1% T-GDS≤10). Outcomes did not differ by trial intervention or time from hospital discharge. CONCLUSIONS AND RELEVANCE: The majority of patients in this large cohort who survived cardiac arrest and were interviewed had no, mild or moderate health impairment. Concern about poor quality of life is not a valid reason to abandon efforts to improve an EMS system's response to cardiac arrest.

Addressing the challenges of obtaining functional outcomes in traumatic brain injury research: missing data patterns, timing of follow-up, and three prognostic models.

Traumatic brain injury (TBI) is common and debilitating. Randomized trials of interventions for TBI ideally assess effectiveness by using long-term functional neurological outcomes, but such outcomes are difficult to obtain and costly. If there is little change between functional status at hospital discharge versus 6 months, then shorter-term outcomes may be adequate for use in future clinical trials. Using data from a previously published multi-center, randomized, placebo-controlled TBI clinical trial, we evaluated patterns of missing outcome data, changes in functional status between hospital discharge and 6 months, and three prognostic models to predict long-term functional outcome from covariates available at hospital discharge (functional measures, demographics, and injury characteristics). The Resuscitation Outcomes Consortium Hypertonic Saline trial enrolled 1282 TBI patients, obtaining the primary outcome of 6-month Glasgow Outcome Score Extended (GOSE) for 85% of patients, but missing the primary outcome for the remaining 15%. Patients with missing outcomes had less-severe injuries, higher neurological function at discharge (GOSE), and shorter hospital stays than patients whose GOSE was obtained. Of 1066 (83%) patients whose GOSE was obtained both at hospital discharge and at 6-months, 71% of patients had the same dichotomized functional status (severe disability/death vs. moderate/no disability) after 6 months as at discharge, 28% had an improved functional status, and 1% had worsened. Performance was excellent (C-statistic between 0.88 and 0.91) for all three prognostic models and calibration adequate for two models (p values, 0.22 and 0.85). Our results suggest that multiple imputation of the standard 6-month GOSE may be reasonable in TBI research when the primary outcome cannot be obtained through other means.