Bacterial Aggregation in Cerebral Spinal Fluid: The Extent it Occurs and the Clinical Ramifications.

Bacteria can form aggregates in synovial fluid that are resistant to antibiotics, but the ability to form aggregates in cerebral spinal fluid (CSF) is poorly defined. Consequently, the aims of this study were to assess the propensity of four bacterial species to form aggregates in CSF under various conditions. To achieve these aims, bacteria were added to CSF in microwell plates and small flasks at static and different dynamic conditions with the aid of an incubating shaker. The aggregates that formed were assessed for antibiotic resistance and the ability of tissue plasminogen activator (TPA) to disrupt these aggregates and reduce the number of bacteria present when used with antibiotics. The results of this study show that under dynamic conditions all four bacteria species formed aggregates that were resistant to high concentrations of antibiotics. Yet with static conditions, no bacteria formed aggregates and when the CSF volume was increased, only Staphylococcus aureus formed aggregates. Interestingly, the aggregates that formed were easily dispersed by TPA and significant (p < 0.005) decreases in colony-forming units were seen when a combination of TPA and antibiotics were compared to antibiotics alone. These findings have clinical significance in that they show bacterial aggregation does not habitually occur in central nervous system infections, but rather occurs under specific conditions. Furthermore, the use of TPA combined with antibiotics may be advantageous in recalcitrant central nervous system infections and this provides a pathophysiological explanation for an unusual finding in the CLEAR III clinical trial.

Neurocritical Care Recovery Clinics: An Idea Whose Time Has Come.

PURPOSE OF REVIEW: Purposes were to identify evidence for post-intensive care syndrome (PICS) and post-intensive care syndrome-family (PICS-F), defined as the psychological impact on families from exposure to critical care, in the neurologically injured population and to characterize existing models for neurorecovery clinics and the evidence to support their use. RECENT FINDINGS: There has been an explosion of post-ICU clinics among the general critical care population, with their use largely justified based on the management of PICS and PICS-F, terminology which excludes brain injured patients. In contrast, neurocritical care recovery clinics are not common and not well-described. There is however evidence in the neuro-ICU population supporting the provision of "dyadic" care, whereby the patient and caregiver are treated as one unit. Brain injured populations likely experience many of the same PICS phenomena as medically ill patients but are not represented in this body of literature. These patients deserve the same level of follow-up as other patients who have experienced critical illness. We propose a neuro-ICU transitional care clinic that addresses PICS-like symptoms and is modeled after transitional care provided to other brain injured populations. Future investigations should be targeted toward understanding the sequalae of a neuro-ICU admission, mechanisms for providing dyadic care, and the impact of neurorecovery clinics on long-term outcomes.

Natural History, Pathophysiology, and Recent Management Modalities of Intraventricular Hemorrhage.

Intraventricular hemorrhage (IVH) is a clinical challenge observed among 40-45% of intracerebral hemorrhage (ICH) cases. IVH can be classified according to the source of the hemorrhage into primary and secondary IVH. Primary intraventricular hemorrhage (PIVH), unlike secondary IVH, involves only the ventricles with no hemorrhagic parenchymal source. Several risk factors of PIVH were reported which include hypertension, smoking, age, and excessive alcohol consumption. IVH is associated with high mortality and morbidity and several prognostic factors were identified such as IVH volume, number of ventricles with blood, involvement of fourth ventricle, baseline Glasgow Coma Scale score, and hydrocephalus. Prompt management of patients with IVH is required to stabilize the clinical status of patients upon admission. Nevertheless, further advanced management is crucial to reduce the morbidity and mortality associated with intraventricular bleeding. Recent treatments showed promising outcomes in the management of IVH patients such as intraventricular anti-inflammatory drugs, lumbar drainage, and endoscopic evacuation of IVH, however, their safety and efficacy are still in question. This literature review presents the epidemiology, physiopathology, risk factors, and outcomes of IVH in adults with an emphasis on recent treatment options.

Leveraging Continuous Vital Sign Measurements for Real-Time Assessment of Autonomic Nervous System Dysfunction After Brain Injury: A Narrative Review of Current and Future Applications.

Subtle and profound changes in autonomic nervous system (ANS) function affecting sympathetic and parasympathetic homeostasis occur as a result of critical illness. Changes in ANS function are particularly salient in neurocritical illness, when direct structural and functional perturbations to autonomic network pathways occur and may herald impending clinical deterioration or intervenable evolving mechanisms of secondary injury. Sympathetic and parasympathetic balance can be measured quantitatively at the bedside using multiple methods, most readily by extracting data from electrocardiographic or photoplethysmography waveforms. Work from our group and others has demonstrated that data-analytic techniques can identify quantitative physiologic changes that precede clinical detection of meaningful events, and therefore may provide an important window for time-sensitive therapies. Here, we review data-analytic approaches to measuring ANS dysfunction from routine bedside physiologic data streams and integrating this data into multimodal machine learning-based model development to better understand phenotypical expression of pathophysiologic mechanisms and perhaps even serve as early detection signals. Attention will be given to examples from our work in acute traumatic brain injury on detection and monitoring of paroxysmal sympathetic hyperactivity and prediction of neurologic deterioration, and in large hemispheric infarction on prediction of malignant cerebral edema. We also discuss future clinical applications and data-analytic challenges and future directions.

Verticalization for Refractory Intracranial Hypertension: A Case Series.

BACKGROUND: Severe intracranial hypertension is strongly associated with mortality. Guidelines recommend medical management involving sedation, hyperosmotic agents, barbiturates, hypothermia, and surgical intervention. When these interventions are maximized or are contraindicated, refractory intracranial hypertension poses risk for herniation and death. We describe a novel intervention of verticalization for treating intracranial hypertension refractory to aggressive medical treatment. METHODS: This study was a single-center retrospective review of six cases of refractory intracranial hypertension in a tertiary care center. All patients were treated with a standard-of-care algorithm for lowering intracranial pressure (ICP) yet maintained an ICP greater than 20 mmHg. They were then treated with verticalization for at least 24 h. We compared the median ICP, the number of ICP spikes greater than 20 mmHg, and the percentage of ICP values greater than 20 mmHg in the 24 h before verticalization vs. after verticalization. We assessed the use of hyperosmotic therapies and any changes in the mean arterial pressure and cerebral perfusion pressure related with the intervention. RESULTS: Five patients were admitted with subarachnoid hemorrhage and one with intracerebral hemorrhage. All patients had ICP monitoring by external ventricular drain. The median opening pressure was 30 mmHg (25th-75th interquartile range 22.5-30 mmHg). All patients demonstrated a reduction in ICP after verticalization, with a significant decrease in the median ICP (12 vs. 8 mmHg; p < 0.001), the number of ICP spikes (12 vs. 2; p < 0.01), and the percentage of ICP values greater than 20 mmHg (50% vs. 8.3%; p < 0.01). There was a decrease in total medical interventions after verticalization (79 vs. 41; p = 0.05) and a lower total therapy intensity level score after verticalization. The most common adverse effects included asymptomatic bradycardia (n = 3) and pressure wounds (n = 4). CONCLUSIONS: Verticalization is an effective noninvasive intervention for lowering ICP in intracranial hypertension that is refractory to aggressive standard management and warrants further study.

Impact of Enteral Albuterol on Bradycardic Events After Acute Cervical Spinal Cord Injury.

BACKGROUND: Acute cervical spinal cord injury (ACSCI) is commonly complicated by spinal shock, resulting in hemodynamic instability characterized by bradycardia and hypotension that can have fatal consequences. Current guidelines recommend the use of intravenous beta and dopamine agonists, such as norepinephrine and dopamine, respectively. We sought to determine whether enteral albuterol would be a safe and feasible treatment for bradycardia without an increase in the occurrence of known side effects of albuterol in patients with ACSCI. METHODS: A retrospective review of patients with ACSCI admitted to an intensive care unit at a level I trauma center and treated with enteral albuterol was conducted. Patients were excluded for the following reasons: pure beta blocker use prior to injury, concurrent use of pacemaker, age of less than 18 years, or age more than 75 years. As part of the standard of care, all patients underwent mean arterial pressure (MAP) augmentation to reach a goal of greater than 85 mm Hg during the first 7 days post injury. All eligible patient charts were reviewed for demographic characteristics, daily minimum and maximum heart rate and MAP, and concomitant vasoactive medication use. Bradycardia and tachycardia were defined as heart rate less than 60 beats per minute (bpm) and greater than 100 bpm, respectively. Factors found to be associated with bradycardia on univariate analysis were entered into a multivariable generalized estimating equation analysis to determine factors independently associated with bradycardia during the study period. RESULTS: There were 58 patients with cervical ASCI (age 45 ± 18 years, 76% men) admitted between January 1, 2016, and December 31, 2017, that met the study criteria. The mean time to initiation of albuterol was 1.5 ± 1.7 days post injury, with a duration of 9.3 ± 4.5 days and a mean daily dosage of 7.8 ± 4.5 mg. Bradycardia was observed in 136 of 766 patient days (17%). There were a few episodes of hyperglycemia (1%) and tachycardia (3%), but no episodes of hypokalemia. In a multivariable analysis, female sex (P = 0.006) and American Spinal Cord Injury Association grade A, B, or C (P < 0.001) were associated with a higher risk of developing bradycardia, whereas dosage of albuterol (P = 0.009) and norepinephrine use (P = 0.008) were associated with a lower risk of developing bradycardia. CONCLUSIONS: Albuterol administration in ASCI is a safe and feasible treatment for bradycardia, given that no significant side effects, such as hyperglycemia, hypokalemia, or tachycardia, were observed. The administration of enteral albuterol was well tolerated and, in a dose-dependent manner, associated with a lower occurrence of bradycardia. Further prospective trials for the use of enteral albuterol after SCI are warranted.

Admission Features Associated With Paroxysmal Sympathetic Hyperactivity After Traumatic Brain Injury: A Case-Control Study.

OBJECTIVES: Paroxysmal sympathetic hyperactivity occurs in a subset of critically ill traumatic brain injury patients and has been associated with worse outcomes after traumatic brain injury. The goal of this study was to identify admission risk factors for the development of paroxysmal sympathetic hyperactivity in traumatic brain injury patients. DESIGN: Retrospective case-control study of age- and Glasgow Coma Scale-matched traumatic brain injury patients. SETTING: Neurotrauma ICU at the R. Adams Cowley Shock Trauma Center of the University of Maryland Medical System, January 2016 to July 2018. PATIENTS: Critically ill adult traumatic brain injury patients who underwent inpatient monitoring for at least 14 days were included. Cases were identified based on treatment for paroxysmal sympathetic hyperactivity with institutional first-line therapies and were confirmed by retrospective tabulation of established paroxysmal sympathetic hyperactivity diagnostic and severity criteria. Cases were matched 1:1 by age and Glasgow Coma Scale to nonparoxysmal sympathetic hyperactivity traumatic brain injury controls, yielding 77 patients in each group. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Admission characteristics independently predictive of paroxysmal sympathetic hyperactivity included male sex, higher admission systolic blood pressure, and initial CT evidence of diffuse axonal injury, intraventricular hemorrhage/subarachnoid hemorrhage, complete cisternal effacement, and absence of contusion. Paroxysmal sympathetic hyperactivity cases demonstrated significantly worse neurologic outcomes upon hospital discharge despite being matched for injury severity at admission. CONCLUSIONS: Several anatomical, epidemiologic, and physiologic risk factors for clinically relevant paroxysmal sympathetic hyperactivity can be identified on ICU admission. These features help characterize paroxysmal sympathetic hyperactivity as a clinical-pathophysiologic phenotype associated with worse outcomes after traumatic brain injury.

Relationship Between Nutrition Intake and Outcome After Subarachnoid Hemorrhage: Results From the International Nutritional Survey.

BACKGROUND: A previous study suggested an association between low caloric intake(CI), negative nitrogen balance, and poor outcome after subarachnoid hemorrhage(SAH). Objective of this multinational, multicenter study was to investigate whether clinical outcomes vary by protein intake(PI) or CI in SAH patients adjusting for the nutritional risk as judged by the modified NUTrition Risk in the Critically Ill (mNUTRIC) score. METHODS: The International Nutrition Survey(INS) 2007-2014 was utilized to describe the characteristics, outcomes and nutrition use. A subgroup of patients from 2013 and 2014(when NUTRIC score was captured) examined the association between CI and PI and time to discharge alive(TTDA) from hospital using Cox regression models, adjusting for nutrition risk classified by the mNUTRIC score as low(0-4) or high(5-9). RESULTS: There were 489 SAH patients(57% female with a mean ± SD age 57.5 ± 13.9 years, BMI of 25.9 ± 5.3 kg/m2 and APACHE-2 score 19.4 ± 7.0. Majority(85%) received enteral nutrition(EN) only, with a time to initiation of EN of 35.4 ± 35.2 hours. 64% had EN interrupted. Patients received a CI of 14.6 ± 7.1 calories/kg/day and PI 0.7 ± 0.3 grams/kg/day corresponding to 59% and 55% of total prescribed CI and PI respectively. In the 2013 and 2014 subgroup there were 226 SAH patients with a mNUTRIC score of 3.4 ± 1.8. Increased CI and PI were associated with faster TTDA among high mNUTRIC patients(HR per 20% of prescription received = 1.34[95% CI,1.03 -1.76] for CI and 1.44[1.07 -1.93] for PI), but not low mNUTRIC patients(CI: HR = 0.95[0.77 -1.16] PI:0.95[0.78 -1.16]). CONCLUSIONS: Results from this multicenter study found that SAH patients received under 60% of their prescribed CI and PI. Further, achieving greater CI and PI in hi risk SAH patients was associated with improved TTDA. mNUTRIC serves to identify SAH patients that benefit most from artificial nutrition and efforts to optimize protein and caloric delivery in this subpopulation should be maximized.

The Modified Fisher Scale Lacks Interrater Reliability.

BACKGROUND: The modified Fisher scale (mFS) is a critical clinical and research tool for risk stratification of cerebral vasospasm. As such, the mFS is included as a common data element by the National Institute of Neurological Disorders and Stroke SAH Working Group. There are few studies assessing the interrater reliability of the mFS. METHODS: We distributed a survey to a convenience sample with snowball sampling of practicing neurointensivists and through the research survey portion of the Neurocritical Care Society Web site. The survey consisted of 15 scrollable CT scans of patients with SAH for mFS grading, two questions regarding the definitions of the scale criteria and demographics of the responding physician. Kendall's coefficient of concordance was used to determine the interrater reliability of mFS grading. RESULTS: Forty-six participants (97.8% neurocritical care fellowship trained, 78% UCNS-certified in neurocritical care, median 5 years (IQR 3-6.3) in practice, treating median of 80 patients (IQR 50-100) with SAH annually from 32 institutions) completed the survey. By mFS criteria, 30% correctly identified that there is no clear measurement of thin versus thick blood, and 42% correctly identified that blood in any ventricle is scored as "intraventricular blood." The overall interrater reliability by Kendall's coefficient of concordance for the mFS was moderate (W = 0.586, p < 0.0005). CONCLUSIONS: Agreement among raters in grading the mFS is only moderate. Online training tools could be developed to improve mFS reliability and standardize research in SAH.

Neuromuscular Electrical Stimulation and High-Protein Supplementation After Subarachnoid Hemorrhage: A Single-Center Phase 2 Randomized Clinical Trial.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (SAH) survivors live with long-term residual physical and cognitive disability. We studied whether neuromuscular electrical stimulation (NMES) and high-protein supplementation (HPRO) in the first 2 weeks after SAH could preserve neuromotor and cognitive function as compared to standard of care (SOC) for nutrition and mobilization. METHODS: SAH subjects with a Hunt Hess (HH) grade > 1,modified Fisher score > 1 and BMI < 40 kg/m2 were randomly assigned to SOC or NMES + HPRO. NMES was delivered to bilateral quadricep muscles daily during two 30-min sessions along with HPRO (goal:1.8 g/kg/day) between post-bleed day (PBD) 0 and 14. Primary endpoint was atrophy in the quadricep muscle as measured by the percentage difference in the cross-sectional area from baseline to PBD14 on CT scan. All subjects underwent serial assessments of physical (short performance physical battery, SPPB) cognitive (Montreal Cognitive Assessment Scale, MoCA) and global functional recovery (modified Rankin Scale, mRS) at PBD 14, 42, and 90. RESULTS: Twenty-five patients (SOC = 13, NMES + HPRO = 12) enrolled between December 2017 and January 2019 with no between-group differences in baseline characteristics (58 years old, 68% women, 50% HH > 3). Median duration of interventions was 12 days (range 9-14) with completion of 98% of NMES sessions and 83% of goal HPRO, and no reported serious adverse events. There was no difference in caloric intake between groups, but HPRO + NMES group received more protein (1.5 ± 0.5 g/kg/d v 0.9 ± 0.4 g/kg/d, P < 0.01). Muscle atrophy was less in NMES + HPRO than the SOC group (6.5 ± 4.1% vs 12.5 ± 6.4%, P 0.01). Higher atrophy was correlated with lower daily protein intake (ρ = - 0.45, P = 0.03) and lower nitrogen balance (ρ = 0.47, P = 0.02); and worse 3 month SPPB (ρ = -  0.31, P = 0.1) and mRS (ρ = 0.4, P = 0.04). NMES + HPRO patients had a better median [25%,75] SPPB (12[10, 12] v. 9 [4, 12], P = 0.01) and mRS (1[0,2] v.2[1, 3], P = 0.04) than SOC at PBD 90. CONCLUSIONS: NMES + HPRO appears to be feasible and safe acutely after SAH and may reduce acute quadriceps muscle wasting with a lasting benefit on recovery after SAH.

Pain Trajectories Following Subarachnoid Hemorrhage are Associated with Continued Opioid Use at Outpatient Follow-up.

BACKGROUND: Subarachnoid hemorrhage (SAH) is characterized by the worst headache of life and associated with long-term opioid use. Discrete pain trajectories predict chronic opioid use following other etiologies of acute pain, but it is unknown whether they exist following SAH. If discrete pain trajectories following SAH exist, it is uncertain whether they predict long-term opioid use. We sought to characterize pain trajectories after SAH and determine whether they are associated with persistent opioid use. METHODS: We reviewed pain scores from patients admitted to a single tertiary care center for SAH from November 2015 to September 2019. Group-based trajectory modeling identified discrete pain trajectories during hospitalization. We compared outcomes across trajectory groups using χ2 and Kruskal-Wallis tests. Multivariable regression determined whether trajectory group membership was an independent predictor of long-term opioid use, defined as continued use at outpatient follow-up. RESULTS: We identified five discrete pain trajectories among 305 patients. Group 1 remained pain free. Group 2 reported low scores with intermittent spikes and slight increase over time. Group 3 noted increasing pain severity through day 7 with mild improvement until day 14. Group 4 experienced maximum pain with steady decrement over time. Group 5 reported moderate pain with subtle improvement. In multivariable analysis, trajectory groups 3 (odds ratio [OR] 3.5; 95% confidence interval [CI] 1.5-8.3) and 5 (OR 8.0; 95% CI 3.1-21.1), history of depression (OR 3.6; 95% CI 1.3-10.0) and racial/ethnic minority (OR 2.3; 95% CI 1.3-4.1) were associated with continued opioid use at follow-up (median 62 days following admission, interquartile range 48-96). CONCLUSIONS: Discrete pain trajectories following SAH exist. Recognition of pain trajectories may help identify those at risk for long-term opioid use.

Triage of Patients with Intracerebral Hemorrhage to Comprehensive Versus Primary Stroke Centers.

OBJECTIVES: The management of patients admitted with intracerebral hemorrhage (ICH) mostly occurs in an ICU. While guidelines recommend initial treatment of these patients in a neurocritical care or stroke unit, there is limited data on which patients would benefit most from transfer to a comprehensive stroke center where on-site neurosurgical coverage is available 24/7. As neurocritical units become more common in primary stroke centers, it is important to determine which patients are most likely to require neurosurgical intervention and transfer to comprehensive stroke centers. MATERIALS AND METHODS: This is a retrospective observational cohort study conducted at an academic comprehensive stroke center in the United States. Four-hundred-fifty-nine consecutive patients transferred or directly admitted to the neurocritical care unit from 2016-2018 with the primary diagnosis of ICH were included. Univariate statistics and multivariate regression were used to identify clinical characteristics associated with neurosurgical intervention, defined as undergoing craniotomy, ventriculostomy, or endovascular embolization of an arteriovenous malformation (AVM). RESULTS: The following variables were associated with neurosurgical intervention in multivariate analysis: age (OR 0.38, 95% CI 0.27-0.55), admission Glasgow Coma Scale (OR 0.29, 95% CI 0.18-0.48), the presence of intraventricular hemorrhage (OR 2.82, CI 1.71-4.65), infratentorial location of ICH (OR 2.28, 95% CI 1.20-4.31), previous antiplatelet use (OR 2.04, 95% CI 1.24-3.34), and an AVM indicated on CT Angiogram (OR 2.59, 95% CI 1.19-5.63) were independently associated with the need for neurosurgical intervention. This was translated into a scoring system to help make quick triage decisions, with high sensitivity (99%, 95% CI 97-99%) and negative predictive value (98%, 95% CI 89-99%). CONCLUSIONS: Using previously well described predictors of severity in ICH patients, we were able to develop a scoring system to predict the need for neurosurgical intervention with high sensitivity and negative predictive value.

Traumatic microbleeds suggest vascular injury and predict disability in traumatic brain injury.

Traumatic microbleeds are small foci of hypointensity seen on T2*-weighted MRI in patients following head trauma that have previously been considered a marker of axonal injury. The linear appearance and location of some traumatic microbleeds suggests a vascular origin. The aims of this study were to: (i) identify and characterize traumatic microbleeds in patients with acute traumatic brain injury; (ii) determine whether appearance of traumatic microbleeds predict clinical outcome; and (iii) describe the pathology underlying traumatic microbleeds in an index patient. Patients presenting to the emergency department following acute head trauma who received a head CT were enrolled within 48 h of injury and received a research MRI. Disability was defined using Glasgow Outcome Scale-Extended ≤6 at follow-up. All magnetic resonance images were interpreted prospectively and were used for subsequent analysis of traumatic microbleeds. Lesions on T2* MRI were stratified based on 'linear' streak-like or 'punctate' petechial-appearing traumatic microbleeds. The brain of an enrolled subject imaged acutely was procured following death for evaluation of traumatic microbleeds using MRI targeted pathology methods. Of the 439 patients enrolled over 78 months, 31% (134/439) had evidence of punctate and/or linear traumatic microbleeds on MRI. Severity of injury, mechanism of injury, and CT findings were associated with traumatic microbleeds on MRI. The presence of traumatic microbleeds was an independent predictor of disability (P < 0.05; odds ratio = 2.5). No differences were found between patients with punctate versus linear appearing microbleeds. Post-mortem imaging and histology revealed traumatic microbleed co-localization with iron-laden macrophages, predominately seen in perivascular space. Evidence of axonal injury was not observed in co-localized histopathological sections. Traumatic microbleeds were prevalent in the population studied and predictive of worse outcome. The source of traumatic microbleed signal on MRI appeared to be iron-laden macrophages in the perivascular space tracking a network of injured vessels. While axonal injury in association with traumatic microbleeds cannot be excluded, recognizing traumatic microbleeds as a form of traumatic vascular injury may aid in identifying patients who could benefit from new therapies targeting the injured vasculature and secondary injury to parenchyma.

Factors associated with tracheostomy decannulation in patients with severe traumatic brain injury.

OBJECTIVE: To assess variables associated with decannulation in patients with traumatic brain injury (TBI). PARTICIPANTS: 79 patients with TBI requiring tracheostomy and ICU admission from January 1st to December 31st, 2014. DESIGN: Retrospective analysis. MEASURES: Patients decannulated prior to 90 days were compared with patients who remained cannulated. Two Cox Proportional Hazards models were used to predict decannulation using variables prior to tracheostomy and throughout hospitalization. RESULTS: Median time to decannulation was 37 days (Interquartile Range [IQR] 29-67). Variables prior to tracheostomy associated with decannulation included diabetes (HR, 0.15; 95% CI, 0.03-0.84; p =.03), craniotomy (HR, 0.25; 95% CI, 0.06-1.02; p =.05) and acute kidney injury (AKI) (HR, 0.06; 95% CI, 0.01-0.48; p =.01). Variables present throughout hospitalization included age (HR, 1.12; 95% CI, 1.01-1.21; p =.03), ventilator days (HR, 0.74; 95% CI, 0.57-0.95; p =.02), reintubation (HR, 0.07; 95% CI, 0.01-0.64; p =.02), aspiration (HR, 0.01; 95% CI, 0.0-0.29, p =.01), craniotomy (HR, 0.004; 95% CI, 0.0-0.39; p =.02) and AKI (HR, 0.0; 95% CI, 0.0-0.21; p =.01). CONCLUSION: The presence of diabetes, craniotomy and acute kidney injury may inform the conversation surrounding chances for decannulation prior to tracheostomy.

Iodine-based Dual-Energy CT of Traumatic Hemorrhagic Contusions: Relationship to In-Hospital Mortality and Short-term Outcome.

BackgroundTraumatic hemorrhagic contusions are associated with iodine leak; however, quantification of leakage and its importance to outcome is unclear.PurposeTo identify iodine-based dual-energy CT variables that correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.Materials and MethodsIn this retrospective study, consecutive patients with contusions from May 2016 through January 2017 were analyzed. Two radiologists evaluated CT variables from unenhanced admission head CT and follow-up head dual-energy CT scans obtained after contrast material-enhanced whole-body CT. The outcomes evaluated were in-hospital mortality, Rancho Los Amigos scale (RLAS) score, and disability rating scale (DRS) score. Logistic regression and linear regression were used to develop prediction models for categorical and continuous outcomes, respectively.ResultsThe study included 65 patients (median age, 48 years; interquartile range, 25-65.5 years); 50 were men. Dual-energy CT variables that correlated with mortality, RLAS score, and DRS score were iodine concentration, pseudohematoma volume, iodine quantity in pseudohematoma, and iodine quantity in contusion. The single-energy CT variable that correlated with mortality, RLAS score, and DRS score was hematoma volume at follow-up CT. Multiple logistic regression analysis after inclusion of clinical variables identified two predictors that enabled determination of mortality: postresuscitation Glasgow coma scale (P-GCS) (adjusted odds ratio, 0.42; 95% confidence interval [CI]: 0.2, 0.86; P = 0.01) and iodine quantity in pseudohematoma (adjusted odds ratio, 1.4 per milligram; 95% CI: 1.02 per milligram, 1.9 per milligram; P = 0.03), with a mean area under the receiver operating characteristic curve of 0.96 ± 0.05 (standard error). For RLAS, the predictors were P-GCS (mean coefficient, 0.32 ± 0.06; P < .001) and iodine quantity in contusion (mean coefficient, -0.04 per milligram ± 0.02; P = 0.01). Predictors for DRS were P-GCS (mean coefficient, -1.15 ± 0.27; P < .001), age (mean coefficient, 0.13 per year ± 0.04; P = .002), and iodine quantity in contusion (mean coefficient, 0.19 per milligram ± 0.07; P = .02).ConclusionIodine-based dual-energy CT variables correlate with in-hospital mortality and short-term outcomes for contusions at hospital discharge.© RSNA, 2019Online supplemental material is available for this article.See also the editorial by Talbott and Hess in this issue.

Inpatient Complications Predict Tracheostomy Better than Admission Variables After Traumatic Brain Injury.

BACKGROUND: Data regarding who will require tracheostomy are lacking which may limit investigations into therapeutic effects of early tracheostomy. METHODS: We performed an observational study of adult traumatic brain injury (TBI) patients requiring intensive care unit (ICU) admission for ≥ 72 h and mechanical ventilation for ≥ 24 h between January 2014 and December 2014 at a level 1 trauma center. Patients who had life-sustaining measures withdrawn were excluded. Multivariable logistic regression analyses were used to assess admission and inpatient factors associated with receiving a tracheostomy and to develop predictive models. Inpatient complications prior to day 7 were used to standardize data collection for patients with and without tracheostomy. Patients who received tracheostomy prior to day 7 were excluded from analysis. RESULTS: In total, 209 patients (78% men, mean 48 years old, median Glasgow Coma Scale score (GCS) 8) met study criteria with tracheostomy performed in 94 (45%). Admission predictors of tracheostomy included GCS, chest tube, Injury Severity Score, and Marshall score. Inpatient factors associated with tracheostomy included the requirement for an external ventricular drain (EVD), number of operations, inpatient dialysis, aspiration, GCS on day 5, and reintubation. Multiple logistic regression analysis demonstrated that the number of operation room trips (adjusted odds ratio [AOR], 1.75; 95% CI, 1.04-2.97; P = 0.036), reintubation (AOR, 8.45; 95% CI, 1.91-37.44; P = .005), and placement of an EVD (AOR, 3.48; 95% CI, 1.27-9.58; P = .016) were independently associated with patients undergoing tracheostomy. Higher GCS on hospital day 5 (AOR, 0.52; 95% CI, 0.40-0.68; P < 0.001) was protective against tracheostomy. A model of inpatient variables only had a stronger association with tracheostomy than one with admission variables only (ROC AUC 0.93 vs 0.72, P < 0.001) and did not benefit from the addition of admission variables (ROC AUC 0.93 vs 0.92, P = 0.78). CONCLUSION: Potentially modifiable inpatient factors have a stronger association with tracheostomy than do admission characteristics. Multicenter studies are needed to validate the results.

Revisiting Grade 3 Diffuse Axonal Injury: Not All Brainstem Microbleeds are Prognostically Equal.

BACKGROUND: Recovery of functional independence is possible in patients with brainstem traumatic axonal injury (TAI), also referred to as "grade 3 diffuse axonal injury," but acute prognostic biomarkers are lacking. We hypothesized that the extent of dorsal brainstem TAI measured by burden of traumatic microbleeds (TMBs) correlates with 1-year functional outcome more strongly than does ventral brainstem, corpus callosal, or global brain TMB burden. Further, we hypothesized that TMBs within brainstem nuclei of the ascending arousal network (AAN) correlate with 1-year outcome. METHODS: Using a prospective outcome database of patients treated for moderate-to-severe traumatic brain injury at an inpatient rehabilitation hospital, we retrospectively identified 39 patients who underwent acute gradient-recalled echo (GRE) magnetic resonance imaging (MRI). TMBs were counted on the acute GRE scans globally and in the dorsal brainstem, ventral brainstem, and corpus callosum. TMBs were also mapped onto an atlas of AAN nuclei. The primary outcome was the disability rating scale (DRS) score at 1 year post-injury. Associations between regional TMBs, AAN TMB volume, and 1-year DRS score were assessed by calculating Spearman rank correlation coefficients. RESULTS: Mean ± SD number of TMBs was: dorsal brainstem = 0.7 ± 1.4, ventral brainstem = 0.2 ± 0.6, corpus callosum = 1.8 ± 2.8, and global = 14.4 ± 12.5. The mean ± SD TMB volume within AAN nuclei was 6.1 ± 18.7 mm3. Increased dorsal brainstem TMBs and larger AAN TMB volume correlated with worse 1-year outcomes (R = 0.37, p = 0.02, and R = 0.36, p = 0.02, respectively). Global, callosal, and ventral brainstem TMBs did not correlate with outcomes. CONCLUSIONS: These findings suggest that dorsal brainstem TAI, especially involving AAN nuclei, may have greater prognostic utility than the total number of lesions in the brain or brainstem.

Super Refractory Status Epilepticus Improved After Emergency Use of Ganaxolone: Case Report.

We present a case of a 34-year-old man with epilepsy who developed super refractory status epilepticus in the setting of COVID-19 pneumonia in whom aggressive therapy with multiple parenteral, enteral, and non-pharmacologic interventions were utilized without lasting improvement in clinical examination or electroencephalogram (EEG). The patient presented with multiple recurrences of electrographic status epilepticus throughout a prolonged hospital stay. Emergency use authorization was obtained for intravenous ganaxolone, a neuroactive steroid that is a potent modulator of both synaptic and extrasynaptic GABAA receptors. Following administration of intravenous ganaxolone according to a novel dosing paradigm, the patient showed sustained clinical and electrographic improvement.

Utilizing ultra-early continuous physiologic data to develop automated measures of clinical severity in a traumatic brain injury population.

Determination of prognosis in the triage process after traumatic brain injury (TBI) is difficult to achieve. Current severity measures like the Trauma and injury severity score (TRISS) and revised trauma score (RTS) rely on additional information from the Glasgow Coma Scale (GCS) and the Injury Severity Score (ISS) which may be inaccurate or delayed, limiting their usefulness in the rapid triage setting. We hypothesized that machine learning based estimations of GCS and ISS obtained through modeling of continuous vital sign features could be used to rapidly derive an automated RTS and TRISS. We derived variables from electrocardiograms (ECG), photoplethysmography (PPG), and blood pressure using continuous data obtained in the first 15 min of admission to build machine learning models of GCS and ISS (ML-GCS and ML-ISS). We compared the TRISS and RTS using ML-ISS and ML-GCS and its value using the actual ISS and GCS in predicting in-hospital mortality. Models were tested in TBI with systemic injury (head abbreviated injury scale (AIS) ≥ 1), and isolated TBI (head AIS ≥ 1 and other AIS ≤ 1). The area under the receiver operating characteristic curve (AUROC) was used to evaluate model performance. A total of 21,077 cases (2009-2015) were in the training set. 6057 cases from 2016 to 2017 were used for testing, with 472 (7.8%) severe TBI (GCS 3-8), 223 (3.7%) moderate TBI (GCS 9-12), and 5913 (88.5%) mild TBI (GCS 13-15). In the TBI with systemic injury group, ML-TRISS had similar AUROC (0.963) to TRISS (0.965) in predicting mortality. ML-RTS had AUROC (0.823) and RTS had AUROC 0.928. In the isolated TBI group, ML-TRISS had AUROC 0.977, and TRISS had AUROC 0.983. ML-RTS had AUROC 0.790 and RTS had AUROC 0.957. Estimation of ISS and GCS from machine learning based modeling of vital sign features can be utilized to provide accurate assessments of the RTS and TRISS in a population of TBI patients. Automation of these scores could be utilized to enhance triage and resource allocation during the ultra-early phase of resuscitation.