Triage of Mild Head-Injured Intoxicated Patients Could Be Aided by Use of an Electroencephalogram-Based Biomarker.

OBJECTIVE: Drug and alcohol (DA)-related emergency department (ED) visits represent an increasing fraction the head-injured population seen in the ED. Such patients present a challenge to the evaluation of head injury and determination of need for computed tomographic (CT) scan and further clinical path. This effort examined whether an electroencephalogram (EEG)-based biomarker could aid in reducing unnecessary CT scans in the intoxicated ED population. METHOD: This is a retrospective secondary study of an independent prospective US Food and Drug Administration validation trial that demonstrated the efficacy of (1) an automatic Structural Injury Classifier for the likelihood of injury visible on a CT (CT+) and (2) an EEG-based Brain Function Index to assess functional impairment in minimally impaired, head-injured adults presenting within 3 days of injury. Impact on the biomarker performance in patients who presented with or without DA was studied. RESULTS: Structural Injury Classifier sensitivity was not significantly impacted by the presence of DA. Although specificity decreased, it remained several times higher than obtained using standard CT decision rules. Furthermore, the potential to reduce the number of unnecessary scans by approximately 30% was demonstrated when the Structural Injury Classifier was integrated into CT clinical triage. The Brain Function Index was demonstrated to be independent of the presence of DA. CONCLUSION: This EEG-based assessment technology used to identify the likelihood of structural or functional brain injury in mildly head-injured patients represents an objective way to aid in triage patients with DA on presentation, with the potential to decrease overscanning while not sacrificing sensitivity to injuries visible on CT.

Emergency Department Time Course for Mild Traumatic Brain Injury Workup.

INTRODUCTION: Mild traumatic brain injury (mTBI) is a common cause for visits to the emergency department (ED). The actual time required for an ED workup of a patient with mTBI in the United States is not well known. National emergency medicine organizations have recommended reducing unnecessary testing, including head computed tomography (CT) for these patients.10. METHODS: To examine this issue, we developed a care map that included each step of evaluation of mTBI (Glasgow Coma Scale Score 13-15) - from initial presentation to the ED to discharge. Time spent at each step was estimated by a panel of United States emergency physicians and nurses. We subsequently validated time estimates using retrospectively collected, real-time data at two EDs. Length of stay (LOS) time differences between admission and discharged patients were calculated for patients being evaluated for mTBI. RESULTS: Evaluation for mTBI was estimated at 401 minutes (6.6 hours) in EDs. Time related to head CT comprised about one-half of the total LOS. Real-time data from two sites corroborated the estimate of median time difference between ED admission and discharge, at 6.3 hours for mTBI. CONCLUSION: Limiting use of head CT as part of the workup of mTBI to more serious cases may reduce time spent in the ED and potentially improve overall ED throughput.

Serum GFAP and UCH-L1 for prediction of absence of intracranial injuries on head CT (ALERT-TBI): a multicentre observational study.

BACKGROUND: More than 50 million people worldwide sustain a traumatic brain injury (TBI) annually. Detection of intracranial injuries relies on head CT, which is overused and resource intensive. Blood-based brain biomarkers hold the potential to predict absence of intracranial injury and thus reduce unnecessary head CT scanning. We sought to validate a test combining ubiquitin C-terminal hydrolase-L1 (UCH-L1) and glial fibrillary acidic protein (GFAP), at predetermined cutoff values, to predict traumatic intracranial injuries on head CT scan acutely after TBI. METHODS: This prospective, multicentre observational trial included adults (≥18 years) presenting to participating emergency departments with suspected, non-penetrating TBI and a Glasgow Coma Scale score of 9-15. Patients were eligible if they had undergone head CT as part of standard emergency care and blood collection within 12 h of injury. UCH-L1 and GFAP were measured in serum and analysed using prespecified cutoff values of 327 pg/mL and 22 pg/mL, respectively. UCH-L1 and GFAP assay results were combined into a single test result that was compared with head CT results. The primary study outcomes were the sensitivity and the negative predictive value (NPV) of the test result for the detection of traumatic intracranial injury on head CT. FINDINGS: Between Dec 6, 2012, and March 20, 2014, 1977 patients were recruited, of whom 1959 had analysable data. 125 (6%) patients had CT-detected intracranial injuries and eight (<1%) had neurosurgically manageable injuries. 1288 (66%) patients had a positive UCH-L1 and GFAP test result and 671 (34%) had a negative test result. For detection of intracranial injury, the test had a sensitivity of 0·976 (95% CI 0·931-0·995) and an NPV of 0·996 (0·987-0·999). In three (<1%) of 1959 patients, the CT scan was positive when the test was negative. INTERPRETATION: These results show the high sensitivity and NPV of the UCH-L1 and GFAP test. This supports its potential clinical role for ruling out the need for a CT scan among patients with TBI presenting at emergency departments in whom a head CT is felt to be clinically indicated. Future studies to determine the value added by this biomarker test to head CT clinical decision rules could be warranted. FUNDING: Banyan Biomarkers and US Army Medical Research and Materiel Command.

A Brain Electrical Activity Electroencephalographic-Based Biomarker of Functional Impairment in Traumatic Brain Injury: A Multi-Site Validation Trial.

The potential clinical utility of a novel quantitative electroencephalographic (EEG)-based Brain Function Index (BFI) as a measure of the presence and severity of functional brain injury was studied as part of an independent prospective validation trial. The BFI was derived using quantitative EEG (QEEG) features associated with functional brain impairment reflecting current consensus on the physiology of concussive injury. Seven hundred and twenty adult patients (18-85 years of age) evaluated within 72 h of sustaining a closed head injury were enrolled at 11 U.S. emergency departments (EDs). Glasgow Coma Scale (GCS) score was 15 in 97%. Standard clinical evaluations were conducted and 5 to 10 min of EEG acquired from frontal locations. Clinical utility of the BFI was assessed for raw scores and percentile values. A multinomial logistic regression analysis demonstrated that the odds ratios (computed against controls) of the mild and moderate functionally impaired groups were significantly different from the odds ratio of the computed tomography (CT) postive (CT+, structural injury visible on CT) group (p = 0.0009 and p = 0.0026, respectively). However, no significant differences were observed between the odds ratios of the mild and moderately functionally impaired groups. Analysis of variance (ANOVA) demonstrated significant differences in BFI among normal (16.8%), mild TBI (mTBI)/concussed with mild or moderate functional impairment, (61.3%), and CT+ (21.9%) patients (p < 0.0001). Regression slopes of the odds ratios for likelihood of group membership suggest a relationship between the BFI and severity of impairment. Findings support the BFI as a quantitative marker of brain function impairment, which scaled with severity of functional impairment in mTBI patients. When integrated into the clinical assessment, the BFI has the potential to aid in early diagnosis and thereby potential to impact the sequelae of TBI by providing an objective marker that is available at the point of care, hand-held, non-invasive, and rapid to obtain.

Correction: Correction to 'Clinical Policy: Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Seizures' [Annals of Emergency Medicine 63 (2014) 437-447.e15].

Due to a miscommunication during the process of transferring this manuscript from our editorial team to Production, the Members of the American College of Emergency Physicians Clinical Policies Committee (Oversight Committee) were not properly indexed in PubMed. This has now been corrected online. The publisher would like to apologize for any inconvenience caused.

Increased prognostic accuracy of TBI when a brain electrical activity biomarker is added to loss of consciousness (LOC).

BACKGROUND: Extremely high accuracy for predicting CT+ traumatic brain injury (TBI) using a quantitative EEG (QEEG) based multivariate classification algorithm was demonstrated in an independent validation trial, in Emergency Department (ED) patients, using an easy to use handheld device. This study compares the predictive power using that algorithm (which includes LOC and amnesia), to the predictive power of LOC alone or LOC plus traumatic amnesia. PARTICIPANTS: ED patients 18-85years presenting within 72h of closed head injury, with GSC 12-15, were study candidates. 680 patients with known absence or presence of LOC were enrolled (145 CT+ and 535 CT- patients). METHODS: 5-10min of eyes closed EEG was acquired using the Ahead 300 handheld device, from frontal and frontotemporal regions. The same classification algorithm methodology was used for both the EEG based and the LOC based algorithms. Predictive power was evaluated using area under the ROC curve (AUC) and odds ratios. RESULTS: The QEEG based classification algorithm demonstrated significant improvement in predictive power compared with LOC alone, both in improved AUC (83% improvement) and odds ratio (increase from 4.65 to 16.22). Adding RGA and/or PTA to LOC was not improved over LOC alone. CONCLUSIONS: Rapid triage of TBI relies on strong initial predictors. Addition of an electrophysiological based marker was shown to outperform report of LOC alone or LOC plus amnesia, in determining risk of an intracranial bleed. In addition, ease of use at point-of-care, non-invasive, and rapid result using such technology suggests significant value added to standard clinical prediction.

Emergency Department Triage of Traumatic Head Injury Using a Brain Electrical Activity Biomarker: A Multisite Prospective Observational Validation Trial.

OBJECTIVES: A brain electrical activity biomarker for identifying traumatic brain injury (TBI) in emergency department (ED) patients presenting with high Glasgow Coma Scale (GCS) after sustaining a head injury has shown promise for objective, rapid triage. The main objective of this study was to prospectively evaluate the efficacy of an automated classification algorithm to determine the likelihood of being computed tomography (CT) positive, in high-functioning TBI patients in the acute state. METHODS: Adult patients admitted to the ED for evaluation within 72 hours of sustaining a closed head injury with GCS 12 to 15 were candidates for study. A total of 720 patients (18-85 years) meeting inclusion/exclusion criteria were enrolled in this observational, prospective validation trial, at 11 U.S. EDs. GCS was 15 in 97%, with the first and third quartiles being 15 (interquartile range = 0) in the study population at the time of the evaluation. Standard clinical evaluations were conducted and 5 to 10 minutes of electroencephalogram (EEG) was acquired from frontal and frontal-temporal scalp locations. Using an a priori derived EEG-based classification algorithm developed on an independent population and applied to this validation population prospectively, the likelihood of each subject being CT+ was determined, and performance metrics were computed relative to adjudicated CT findings. RESULTS: Sensitivity of the binary classifier (likely CT+ or CT-) was 92.3% (95% confidence interval [CI] = 87.8%-95.5%) for detection of any intracranial injury visible on CT (CT+), with specificity of 51.6% (95% CI = 48.1%-55.1%) and negative predictive value (NPV) of 96.0% (95% CI = 93.2%-97.9%). Using ternary classification (likely CT+, equivocal, likely CT-) demonstrated enhanced sensitivity to traumatic hematomas (≥1 mL of blood), 98.6% (95% CI = 92.6%-100.0%), and NPV of 98.2% (95% CI = 95.5%-99.5%). CONCLUSION: Using an EEG-based biomarker high accuracy of predicting the likelihood of being CT+ was obtained, with high NPV and sensitivity to any traumatic bleeding and to hematomas. Specificity was significantly higher than standard CT decision rules. The short time to acquire results and the ease of use in the ED environment suggests that EEG-based classifier algorithms have potential to impact triage and clinical management of head-injured patients.

Neuro-Ophthalmology in Emergency Medicine.

Understanding the anatomy and physiology of the eye, the orbit, and the central connections is key to understanding neuro-ophthalmologic emergencies. Anisocoria is an important sign that requires a systematic approach to avoid misdiagnosis of serious conditions, including carotid dissection (miosis) and aneurysmal third nerve palsy (mydriasis). Ptosis may be a sign of either Horner syndrome or third nerve palsy. An explanation should be pursued for diplopia since the differential diagnosis ranges from the trivial to life-threatening causes.

Classification algorithms for the identification of structural injury in TBI using brain electrical activity.

BACKGROUND: There is an urgent need for objective criteria adjunctive to standard clinical assessment of acute Traumatic Brain Injury (TBI). Details of the development of a quantitative index to identify structural brain injury based on brain electrical activity will be described. METHODS: Acute closed head injured and normal patients (n=1470) were recruited from 16 US Emergency Departments and evaluated using brain electrical activity (EEG) recorded from forehead electrodes. Patients had high GCS (median=15), and most presented with low suspicion of brain injury. Patients were divided into a CT positive (CT+) group and a group with CT negative findings or where CT scans were not ordered according to standard assessment (CT-/CT_NR). Three different classifier methodologies, Ensemble Harmony, Least Absolute Shrinkage and Selection Operator (LASSO), and Genetic Algorithm (GA), were utilized. RESULTS: Similar performance accuracy was obtained for all three methodologies with an average sensitivity/specificity of 97.5%/59.5%, area under the curves (AUC) of 0.90 and average Negative Predictive Validity (NPV)>99%. Sensitivity was highest for CT+ cases with potentially life threatening hematomas, where two of three classifiers were 100%. CONCLUSION: Similar performance of these classifiers suggests that the optimal separation of the populations was obtained given the overlap of the underlying distributions of features of brain activity. High sensitivity to CT+ injuries (highest in hematomas) and specificity significantly higher than that obtained using ED guidelines for imaging, supports the enhanced clinical utility of this technology and suggests the potential role in the objective, rapid and more optimal triage of TBI patients.

Syncope: risk stratification and clinical decision making.

Syncope is a common occurrence in the emergency department, accounting for approximately 1% to 3% of presentations. Syncope is best defined as a brief loss of consciousness and postural tone followed by spontaneous and complete recovery. The spectrum of etiologies ranges from benign to life threatening, and a structured approach to evaluating these patients is key to providing care that is thorough, yet cost-effective. This issue reviews the most relevant evidence for managing and risk stratifying the syncope patient, beginning with a focused history, physical examination, electrocardiogram, and tailored diagnostic testing. Several risk stratification decision rules are compared for performance in various scenarios, including how age and associated comorbidities may predict short-term and long-term adverse events. An algorithm for structured, evidence-based care of the syncope patient is included to ensure that patients requiring hospitalization are managed appropriately and those with benign causes are discharged safely.

Nonurgent commercial air travel after nonhemorrhagic cerebrovascular accident.

Nonurgent commercial air travel in patients who have experienced a nonhemorrhagic cerebrovascular accident (CVA) may occur, particularly in the elderly traveling population. A recent CVA, particularly occurring during a person's travel, presents a significant challenge to the patient, companions, family, and health care team. Specific medical recommendation, based on accumulated scientific data and interpreted by medical experts, is needed so that travel health care professionals can appropriately guide the patient. Unfortunately, such recommendations are almost entirely lacking despite the relative frequency of CVA and air travel. This article reviews the existing recommendations with conclusions based on both these limited data and rationale conjecture.

Air travel of patients with abdominal aortic aneurysm: urgent air medical evacuation and nonurgent commercial air repatriation.

Abdominal aortic aneurysm (AAA) presents across a spectrum of severity. Although some resources suggest a theoretic risk for rupture related to air travel, this claim remains unproven. In fact, there are little data from which to make evidence-based recommendations. Air medical evacuation of a patient with either an AAA at risk of imminent rupture or status post recent rupture can be performed, assuming that local surgical care is not available and that transfer is taking the patient to a higher level of medical intervention. Furthermore, medical opinion suggests that patients with asymptomatic and/or surgically corrected AAA can safely travel by commercial aircraft for nonurgent reasons, assuming that other issues including postoperative needs are appropriately addressed. In this discussion, answers to the following issues are sought: flight safety for urgent evacuation and nonurgent repatriation scenarios, waiting time to fly nonurgently after AAA diagnosis, and the need for medical accompaniment.

Differences in interpretation of cranial computed tomography in ED traumatic brain injury patients by expert neuroradiologists.

Cranial computed tomography (CT) is generally regarded as the standard for evaluation of structural brain injury in patients with traumatic brain injury (TBI) presenting to the emergency department (ED). However, the subjective nature of the visual interpretations of CT scans and the qualitative nature of reporting may lead to poor interrater reliability. This is significant because CT positive scans include a continuum of structural injury with differences in treatment. The purpose of the present study was to evaluate the consistency of readings of head CT scans obtained within 24 hours after mild TBI in the ED, as assessed by an independent adjudication panel of 3 experienced neuroradiologists. In 80.1% of the cases, all 3 adjudicators agreed with the determination of the presence of structural injury. However, when interrater agreement was assessed with respect to the specific classification of the injury, agreement was poor, with a κ of 0.3 (0.29-0.316; confidence interval [CI] 95%). When classification was collapsed, considering only the presence or absence of hematomas, agreement among all 3 adjudicators improved to 55%, but the κ of 0.355, (0.332-0.78; CI 95%) was still only fair. The data suggest the need for improved recognition and quantification of specific structural injuries in the TBI population for better identification of patients requiring clinical intervention.

Clinical policy: critical issues in the evaluation and management of adult patients presenting to the emergency department with seizures.

This clinical policy from the American College of Emergency Physicians is the revision of a 2004 policy on critical issues in the evaluation and management of adult patients with seizures in the emergency department. A writing subcommittee reviewed the literature to derive evidence-based recommendations to help clinicians answer the following critical questions: (1) In patients with a first generalized convulsive seizure who have returned to their baseline clinical status, should antiepileptic therapy be initiated in the emergency department to prevent additional seizures? (2) In patients with a first unprovoked seizure who have returned to their baseline clinical status in the emergency department, should the patient be admitted to the hospital to prevent adverse events? (3) In patients with a known seizure disorder in which resuming their antiepileptic medication in the emergency department is deemed appropriate, does the route of administration impact recurrence of seizures? (4) In emergency department patients with generalized convulsive status epilepticus who continue to have seizures despite receiving optimal dosing of a benzodiazepine, which agent or agents should be administered next to terminate seizures? A literature search was performed, the evidence was graded, and recommendations were given based on the strength of the available data in the medical literature.

Emergency neurological life support: intracranial hypertension and herniation.

Sustained intracranial hypertension and acute brain herniation are "brain codes," signifying catastrophic neurological events that require immediate recognition and treatment to prevent irreversible injury and death. As in cardiac arrest, evidence supports the organized implementation of a stepwise management algorithm. Because there are multiple etiologies and many treatments that can potentially reverse cerebral herniation, intracranial hypertension and herniation was chosen as an Emergency Neurological Life Support (ENLS) protocol.

Emergency neurological life support: approach to the patient with coma.

Coma is an acute failure of neuronal systems governing arousal and awareness and represents a neurological emergency. When encountering a comatose patient, the clinician must have an organized approach to detect easily remedial causes, prevent ongoing neurologic injury, and determine a hierarchy of diagnostic tests, treatments, and neuromonitoring. Coma was chosen as an Emergency Neurological Life Support (ENLS) protocol because timely medical and surgical interventions can be life-saving, and the initial work-up of such patients is critical to establishing a correct diagnosis.

Pathophysiology and definitions of seizures and status epilepticus.

The pathophysiology of seizures is multifactorial and incompletely understood. Experimental work demonstrates that prolonged, abnormal, and excessive neuronal electrical activity in itself is injurious through several mechanisms independent of systemic acidosis and hypoxia. Population survival studies and laboratory investigations support the idea that brain injury and epileptogenesis result from status epilepticus. The basic distinction in seizure types is that of generalized and partial seizures. Correct classification of seizure types will aid in clinical communications and guide correct therapies. Revised definitions of generalized convulsive status epilepticus suggest making this diagnosis with as few as 5 minutes of continuous seizure activity.