Smartphone Use in the Management of Neurological Emergencies: A Simulation-Based Study.

BACKGROUND: Smartphone use in medicine is nearly universal despite a dearth of research assessing utility in clinical performance. We sought to identify and define smartphone use during simulated neuroemergencies. METHODS: In this retrospective review of a prospective observational single-center simulation-based study, participants ranging from subinterns to attending physicians and stratified by training level (novice, intermediate, and advanced) managed a variety of neurological emergencies. The primary outcome was frequency and purpose of smartphone use. Secondary outcomes included success rate of smartphone use and performance (measured by completion of critical tasks) of participants who used smartphones versus those who did not. In subgroup analyses we compared outcomes across participants by level of training using t-tests and χ2 statistics. RESULTS: One hundred and three participants completed 245 simulation scenarios. Smartphones were used in 109 (45%) simulations. Of participants using smartphones, 102 participants looked up medication doses, 52 participants looked up management guidelines, 11 participants looked up hospital protocols, and 13 participants used smartphones for assistance with an examination scale. Participants found the correct answer 73% of the time using smartphones. There was an association between participant level and smartphone use with intermediate participants being more likely to use their smartphones than novice or advanced participants, 53% versus 29% and 26%, respectively (p < 0.05). Of the intermediate participants, those who used smartphones did not perform better during the simulation scenario than participants who did not use smartphones (smartphone users' mean score [standard deviation] = 12.3 [2.9] vs. nonsmartphone users' mean score [standard deviation] = 12.9 (2.7), p = 0.85). CONCLUSIONS: Participants commonly used smartphones in simulated neuroemergencies but use didn't confer improved clinical performance. Less experienced participants were the most likely to use smartphones and less likely to arrive at correct conclusions, and thus are the most likely to benefit from an evidence-based smartphone application for neuroemergencies.

Comparison of induction agents for rapid sequence intubation in refractory status epilepticus: A single-center retrospective analysis.

Endotracheal intubation, frequently required during management of refractory status epilepticus (RSE), can be facilitated by anesthetic medications; however, their effectiveness for RSE control is unknown. We performed a single-center retrospective review of patients admitted to a neurocritical care unit (NCCU) who underwent in-hospital intubation during RSE management. Patients intubated with propofol, ketamine, or benzodiazepines, termed anti-seizure induction (ASI), were compared to patients who received etomidate induction (EI). The primary endpoint was clinical or electrographic seizures within 12 h post-intubation. We estimated the association of ASI on post-intubation seizure using logistic regression. A sub-group of patients undergoing electroencephalography during intubation was identified to evaluate the immediate effect of ASI on RSE. We screened 697 patients admitted to the NCCU for RSE and identified 148 intubated in-hospital (n = 90 ASI, n = 58 EI). There was no difference in post-intubation seizure (26 % (n = 23) ASI, 29 % (n = 17) EI) in the cohort, however, there was increased RSE resolution with ASI in 24 patients with electrographic RSE during intubation (ASI: 61 % (n = 11/18) vs EI: 0 % (n = 0/6), p =.016). While anti-seizure induction did not appear to affect post-intubation seizure occurrence overall, a sub-group of patients undergoing electroencephalography during intubation had a higher incidence of seizure cessation, suggesting potential benefit in an enriched population.

Iodine-based dual-energy CT predicts early neurological decline from cerebral edema after large hemispheric infarction.

Background & Purpose: Ischemia affecting two thirds of the MCA territory predicts development of malignant cerebral edema. However, early infarcts are hard to diagnose on conventional head CT. We hypothesize that high-energy (190keV) virtual monochromatic images (VMI) from dual-energy CT (DECT) imaging enables earlier detection of secondary injury from malignant cerebral edema (MCE). Methods: Consecutive LHI patients with NIHSS ≥ 15 and DECT within 10 hours of reperfusion from May 2020 to March 2022 were included. We excluded patients with parenchymal hematoma-type 2 transformation. Retrospective analysis of clinical and novel variables included VMI Alberta Stroke Program Early CT Score (ASPECTS), total iodine content, and VMI infarct volume. Primary outcome was early neurological decline (END). Secondary outcomes included hemorrhagic transformation, decompressive craniectomy (DC), and medical treatment of MCE. Fisher's exact test and Wilcoxon test were used for univariate analysis. Logistic regression was used to develop prediction models for categorical outcomes. Results: Eighty-four LHI patients with a median age of 67.5 [IQR 57,78] years and NIHSS 22 [IQR 18,25] were included. Twenty-nine patients had END. VMI ASPECTS, total iodine content, and VMI infarct volume were associated with END. VMI ASPECTS, VMI infarct volume, and total iodine content were predictors of END after adjusting for age, sex, initial NIHSS, and tPA administration, with a AUROC of 0.691 [0.572,0.810], 0.877 [0.800, 0.954], and 0.845 [0.750, 0.940]. By including all three predictors, the model achieved AUROC of 0.903 [0.84,0.97] and was cross validated by leave one out method with AUROC of 0.827. Conclusion: DECT with high-energy VMI and iodine quantification is superior to conventional CT ASPECTS and is a novel predictor for early neurological decline due to malignant cerebral edema after large hemispheric infarction.

Steroids Provide Temporary Improvement of Refractory Pain Following Subarachnoid Hemorrhage.

Introduction: Evidence for optimal analgesia following subarachnoid hemorrhage (SAH) is limited. Steroid therapy for pain refractory to standard regimens is common despite lack of evidence for its efficacy. We sought to determine if steroids reduced pain or utilization of other analgesics when given for refractory headache following SAH. Methods: We performed a retrospective within-subjects cohort study of SAH patients who received steroids for refractory headache. We compared daily pain scores, total daily opioid, and acetaminophen doses before, during, and after steroids. Repeated measures were analyzed with a multivariable general linear model and generalized estimating equations. Results: Included 52 patients treated with dexamethasone following SAH, of whom 11 received a second course, increasing total to 63 treatment epochs. Mean pain score on the first day of therapy was 7.92 (standard error of the mean [SEM] .37) and decreased to 6.68 (SEM .36) on the second day before quickly returning to baseline levels, 7.36 (SEM .33), following completion of treatment. Total daily analgesics mirrored this trend. Mean total opioid and acetaminophen doses on days one and two and two days after treatment were 47.83mg (SEM 6.22) and 1848mg (SEM 170.66), 34.24mg (SEM 5.12) and 1809mg (SEM 150.28), and 46.38mg (SEM 11.64) and 1833mg (SEM 174.23), respectively. Response to therapy was associated with older age, decreasing acetaminophen dosing, and longer duration of steroids. Hyperglycemia and sleep disturbance/delirium effected 28.6% and 55.6% of cases, respectively. Conclusion: Steroid therapy for refractory pain in SAH patients may have modest, transient effects in select patients.

Prediction of blood pressure variability during thrombectomy using supervised machine learning and outcomes of patients with ischemic stroke from large vessel occlusion.

Mechanical thrombectomy (MT) is the standard of care for patients with acute ischemic stroke from large vessel occlusion (AIS-LVO). The association of blood pressure variability (BPV) during MT and outcomes are unknown. We leveraged a supervised machine learning algorithm to predict patient characteristics that are associated with BPV indices. We performed a retrospective review of our comprehensive stroke center's registry of all adult patients undergoing MT between 01/01/2016 and 12/31/2019. The primary outcome was poor functional independence, defined as 90-day modified Rankin Scale (mRS) ≥ 3. We used probit analysis and multivariate logistic regressions to evaluate the association of patients' clinical factors and outcomes. We applied a machine learning algorithm (random forest, RF) to determine predictive factors for the different BPV indices during MT. Evaluation was performed with root-mean-square error (RMSE) and normalized-RMSE (nRMSE) metrics. We analyzed 375 patients with mean age (± standard deviation [SD]) of 65 (15) years. There were 234 (62%) patients with mRS ≥ 3. Univariate probit analysis demonstrated that BPV during MT was associated with poor functional independence. Multivariable logistic regression showed that age, admission National Institutes of Health Stroke Scale (NIHSS), mechanical ventilation, and thrombolysis in cerebral infarction (TICI) score (OR 0.42, 95% CI 0.17-0.98, P = 0.044) were significantly associated with outcome. RF analysis identified that the interval from last-known-well time-to-groin puncture, age, and mechanical ventilation were among important factors significantly associated with BPV. BPV during MT was associated with functional outcome in univariate probit analysis but not in multivariable regression analysis, however, NIHSS and TICI score were. RF algorithm identified risk factors influencing patients' BPV during MT. While awaiting further studies' results, clinicians should still monitor and avoid high BPV during thrombectomy while triaging AIS-LVO candidates quickly to MT.

Intracranial and Blood Pressure Variability and In-Hospital Outcomes in Intracranial Device-Monitored Patients with Spontaneous Intracerebral Hemorrhage.

BACKGROUND: Spontaneous intracerebral hemorrhage (sICH) is a major health concern and has high mortality rates up to 52%. Despite a decrease in its incidence, fatality rates remain unchanged; understanding and preventing of factors associated with mortality and treatments for these are needed. Blood pressure variability (BPV) has been shown to be a potential modifiable factor associated with clinical outcomes in patients with traumatic intracerebral hemorrhage and sICH. Few data are available on the effect of intracranial pressure (ICP) variability (ICPV) and outcomes in patients with sICH. The goal of our study was to investigate the association between ICPV and BPV during the first 24 h of intensive care unit (ICU) admission and external ventricular drain (EVD) placement, and mortality in patients with sICH who were monitored with an EVD. METHODS: We conducted a single-center retrospective study of adult patients admitted to an ICU with a diagnosis of sICH who required EVD placement during hospitalization. We excluded patients with ICH secondary to other pathological conditions such as trauma, underlying malignancy, or arteriovenous malformation. Blood pressure and ICP measurements were collected and recorded hourly during the first 24 h of ICU admission and EVD placement, respectively. Measures of variability used were standard deviation (SD) and successive variation (SV). Primary outcome of interest was in-hospital mortality, and secondary outcomes were hematoma expansion and discharge home (a surrogate for good functional outcome at discharge). Descriptive statistics and multivariable logistic regressions were performed. RESULTS: We identified 179 patients with sICH who required EVD placement. Of these, 52 (29%) patients died, 121 (68%) patients had hematoma expansion, and 12 (7%) patients were discharged home. Patient's mean age (± SD) was 56 (± 14), and 87 (49%) were women. The mean opening ICP (± SD) was 21 (± 8) and median ICH score (interquartile range) was 2 (2-3). Multivariable logistic regression found an association between ICP-SV and ICP-SD and hematoma expansion (odds ratio 1.6 [1.03-2.30], p = 0.035 and odds ratio 0.77 [0.63-0.93] p = 0.009, respectively). CONCLUSIONS: Our study found an association between ICPV and hematoma expansion in patients with sICH monitored with an EVD. Measures of ICPV relating to rapid changes in ICP (ICP-SV) were associated with a higher odds of hematoma expansion, whereas measures relating to tight control of ICP (ICP-SD) were associated with a lower odds of hematoma expansion. One measure of BPV, sytolic blood pressure maximum-minimum (SBP max-min), was found to be weakly associated with discharge home (a surrogate for good functional outcome at hospital discharge). More research is needed to support these findings.

Simulation-based assessment of trainee's performance in post-cardiac arrest resuscitation.

Objectives: To assess trainees' performance in managing a patient with post-cardiac arrest complicated by status epilepticus. Methods: In this prospective, observational, single-center simulation-based study, trainees ranging from sub interns to critical care fellows evaluated and managed a post cardiac arrest patient, complicated by status epilepticus. Critical action items were developed by a modified Delphi approach based on American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurological Life Support protocols. The primary outcome measure was the critical action item sum score. We sought validity evidence to support our findings by including attending neurocritical care physicians and comparing performance across four levels of training. Results: Forty-nine participants completed the simulation. The mean sum of critical actions completed by trainees was 10/21 (49%). Eleven (22%) trainees verbalized a differential diagnosis for the arrest. Thirty-two (65%) reviewed the electrocardiogram, recognized it as abnormal, and consulted cardiology. Forty trainees (81%) independently decided to start temperature management, but only 20 (41%) insisted on it when asked to reconsider. There was an effect of level of training on critical action checklist sum scores (novice mean score [standard deviation (SD)] = 4.8(1.8) vs. intermediate mean score (SD) = 10.4(2.1) vs. advanced mean score (D) = 11.6(3.0) vs. expert mean score (SD) = 14.7(2.2)). Conclusions: High-fidelity manikin-based simulation holds promise as an assessment tool in the performance of post-cardiac arrest care.

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.

Simulation-Based Assessment of Graduate Neurology Trainees' Performance Managing Acute Ischemic Stroke.

BACKGROUND AND OBJECTIVES: Multidisciplinary acute stroke teams improve acute ischemic stroke management but may hinder trainees' education, which in turn may contribute to poorer outcomes in community hospitals on graduation. Our goal was to assess graduate neurology trainee performance independently of a multidisciplinary stroke team in the management of acute ischemic stroke, tissue plasminogen activator (tPA)-related hemorrhage, and cerebral herniation syndrome. METHODS: In this prospective, observational, single-center simulation-based study, participants (subinterns to attending physicians) managed a patient with acute ischemic stroke followed by tPA-related hemorrhagic conversion leading to cerebral herniation. Critical actions were developed by a modified Delphi approach based on relevant American Heart Association guidelines and the Neurocritical Care Society's Emergency Neurologic Life Support protocols. The primary outcome measure was graduate neurology trainees' critical action item sum score. We sought validity evidence to support our findings by comparing performance across 4 levels of training. RESULTS: Fifty-three trainees (including 31 graduate neurology trainees) and 5 attending physicians completed the simulation. The mean sum of critical actions completed by graduate neurology trainees was 15 of 22 (68%). Ninety percent of graduate neurology trainees properly administered tPA; 84% immediately stopped tPA infusion after patient deterioration; but only 55% reversed tPA according to guidelines. There was a moderately strong effect of level of training on critical action sum score (level 1 mean [SD] score 7.2 [2.8] vs level 2 mean [SD] score 12.3 [2.6] vs level 3 mean [SD] score 13.3 [2.2] vs level 4 mean [SD] score 16.3 [2.4], p < 0.001, R 2 = 0.54). DISCUSSION: Graduate neurology trainees reassuringly perform well in initial management of acute ischemic stroke but frequently make errors in the treatment of hemorrhagic transformation after thrombolysis, suggesting the need for more education surrounding this low-frequency, high-acuity event. High-fidelity simulation holds promise as an assessment tool for acute stroke management performance.

An update on the pharmacological management and prevention of cerebral edema: current therapeutic strategies.

Introduction: Cerebral edema is a common complication of multiple neurological diseases and is a strong predictor of outcome, especially in traumatic brain injury and large hemispheric infarction.Areas Covered: Traditional and current treatments of cerebral edema include treatment with osmotherapy or decompressive craniectomy at the time of clinical deterioration. The authors discuss preclinical and clinical models of a variety of neurological disease states that have identified receptors, ion transporters, and channels involved in the development of cerebral edema as well as modulation of these receptors with promising agents.Expert opinion: Further study is needed on the safety and efficacy of the agents discussed. IV glibenclamide has shown promise in preclinical and clinical trials of cerebral edema in large hemispheric infarct and traumatic brain injury. Consideration of underlying pathophysiology and pharmacodynamics is vital, as the synergistic use of agents has the potential to drastically mitigate cerebral edema and secondary brain injury thusly transforming our treatment paradigms.

BIIB093 (IV glibenclamide): an investigational compound for the prevention and treatment of severe cerebral edema.

Introduction: Brain swelling due to edema formation is a major cause of neurological deterioration and death in patients with large hemispheric infarction (LHI) and severe traumatic brain injury (TBI), especially contusion-TBI. Preclinical studies have shown that SUR1-TRPM4 channels play a critical role in edema formation and brain swelling in LHI and TBI. Glibenclamide, a sulfonylurea drug and potent inhibitor of SUR1-TRPM4, was reformulated for intravenous injection, known as BIIB093.Areas covered: We discuss the findings from Phase 2 clinical trials of BIIB093 in patients with LHI (GAMES-Pilot and GAMES-RP) and from a small Phase 2 clinical trial in patients with TBI. For the GAMES trials, we review data on objective biological variables, adjudicated edema-related endpoints, functional outcomes, and mortality which, despite missing the primary endpoint, supported the initiation of a Phase 3 trial in LHI (CHARM). For the TBI trial, we review data on MRI measures of edema and the initiation of a Phase 2 trial in contusion-TBI (ASTRAL).Expert opinion: Emerging clinical data show that BIIB093 has the potential to transform our management of patients with LHI, contusion-TBI and other conditions in which swelling leads to neurological deterioration and death.

Octogenarian Reports of Lifetime Spiritual Experiences: Types of Experience and Early Life Predictors.

This study assessed lifetime histories of discrete spiritual experiences recalled by 144 octogenarian men studied since adolescence and 80 spouses. Women were more likely to report discrete spiritual experiences, as were those from higher socioeconomic backgrounds and those judged more open to experience as young adults. Factor analysis revealed four types of experiences related to beauty/nature, negative life events, protection by a sacred other, and traditional religious settings. Men from better childhood environments more commonly reported spiritual experiences concerning negative life events. Those with serious childhood illnesses were less likely to report experiences of feeling protected by a sacred other.