Multimodal Neurologic Monitoring in Patients Undergoing Extracorporeal Membrane Oxygenation.

Introduction Extracorporeal membrane oxygenation (ECMO) is associated with a high rate of neurologic complications. Multimodal neurologic monitoring (MNM) has the potential for early detection and intervention. We examined the safety and feasibility of noninvasive MNM during ECMO. We hypothesized that survivors and non-survivors would have meaningful differences in transcranial Doppler (TCD) sonography and electroencephalographic (EEG) characteristics, which we aimed to identify. We also investigated adverse neurologic events and attempted to identify differences in EEG and TCD characteristics among patients based on the type of ECMO and the occurrence of these events. Material and methods We performed an observational study on all patients undergoing ECMO at Baylor St. Luke's Medical Center's critical care unit in Houston, Texas, United States, from January 2017 to February 2019. All patients underwent a noninvasive MNM protocol. Results NM was completed in 75% of patients; all patients received at least one component of the monitoring protocol. No adverse events were noted, showing the feasibility and safety of the protocol. The 60.4% of patients who did not survive tended to be older, had lower ejection fractions, and had lower median right middle cerebral artery (MCA) pulsatility and resistivity indexes. Patients undergoing venoarterial (VA)-ECMO had lower median left and right MCA velocities and lower right Lindegaard ratios than patients who underwent venovenous-ECMO. In VA-ECMO patients, EEG less often showed sleep architecture, while other findings were similar between groups. Adverse neurologic events occurred in 24.7% of patients, all undergoing VA-ECMO. Acute ischemic stroke occurred in 22% of patients, intraparenchymal hemorrhage in 4.9%, hypoxic-ischemic encephalopathy in 3.7%, subarachnoid hemorrhage in 2.5%, and subdural hematoma in 1.2%. Conclusion Our results suggest that MNM is safe and feasible for patients undergoing ECMO. Certain EEG and TCD findings could aid in the early detection of neurologic deterioration. MNM may not just be used in monitoring patients undergoing ECMO but also in prognostication and aiding clinical decision-making.

Regional Variability in the Care and Outcomes of Subarachnoid Hemorrhage Patients in the United States.

Background and Objectives: Regional variability in subarachnoid hemorrhage (SAH) care is reported in physician surveys. We aimed to describe variability in SAH care using patient-level data and identify factors impacting hospital outcomes and regional variability in outcomes. Methods: A retrospective multi-center cross-sectional cohort study of consecutive non-traumatic SAH patients in the Vizient Clinical Data Base, between January 1st, 2009 and December 30th, 2018 was performed. Participating hospitals were divided into US regions: Northeast, Midwest, South, West. Regional demographics, co-morbidities, severity-of-illness, complications, interventions and discharge outcomes were compared. Multivariable logistic regression was performed to identify factors independently associated with primary outcomes: hospital mortality and poor discharge outcome. Poor discharge outcome was defined by the Nationwide Inpatient Sample-SAH Outcome Measure, an externally-validated outcome measure combining death, discharge disposition, tracheostomy and/or gastrostomy. Regional variability in the associations between care and outcomes were assessed by introducing an interaction term for US region into the models. Results: Of 109,034 patients included, 24.3% were from Northeast, 24.9% Midwest, 34.9% South, 15.9% West. Mean (SD) age was 58.6 (15.6) years and 64,245 (58.9%) were female. In-hospital mortality occurred in 21,991 (20.2%) and 44,159 (40.5%) had poor discharge outcome. There was significant variability in severity-of-illness, co-morbidities, complications and interventions across US regions. Notable findings were higher prevalence of surgical clipping (18.8 vs. 11.6%), delayed cerebral ischemia (4.3 vs. 3.1%), seizures (16.5 vs. 14.8%), infections (18 vs. 14.7%), length of stay (mean [SD] days; 15.7 [19.2] vs. 14.1 [16.7]) and health-care direct costs (mean [SD] USD; 80,379 [98,999]. vs. 58,264 [74,430]) in the West when compared to other regions (all p < 0.0001). Variability in care was also associated with modest variability in hospital mortality and discharge outcome. Aneurysm repair, nimodipine use, later admission-year, endovascular rescue therapies reduced the odds for poor outcome. Age, severity-of-illness, co-morbidities, hospital complications, and vasopressor use increased those odds (c-statistic; mortality: 0.77; discharge outcome: 0.81). Regional interaction effect was significant for admission severity-of-illness, aneurysm-repair and nimodipine-use. Discussion: Multiple hospital-care factors impact SAH outcomes and significant variability in hospital-care and modest variability in discharge-outcomes exists across the US. Variability in SAH-severity, nimodipine-use and aneurysm-repair may drive variability in outcomes.

Implementation of systematic safety checklists in a neurocritical care unit: a quality improvement study.

BACKGROUND AND OBJECTIVES: Structured and systematised checklists have been shown to prevent complications and improve patient care. We evaluated the implementation of systematic safety checklists in our neurocritical care unit (NCCU) and assessed its effect on patient outcomes. DESIGN/METHODS: This quality improvement project followed a Plan-Do-Study-Act (PDSA) methodology. A checklist for medication reconciliation, thromboembolic prophylaxis, glycaemic control, daily spontaneous awakening, breathing trial, diet, catheter/lines duration monitoring and antibiotics de-escalation was implemented during daily patient rounds. Main outcomes included the rate of new infections, mortality and NCCU-length of stay (LOS). Intervened patients were compared with historical controls after propensity score and Euclidean distance matching to balance baseline covariates. RESULTS: After several PDSA iterations, we applied checklists to 411 patients; the overall average age was 61.34 (17.39). The main reason for admission included tumour resection (31.39%), ischaemic stroke (26.76%) and intracerebral haemorrhage (10.95%); the mean Sequential Organ Failure Assessment (SOFA) score was 2.58 (2.68). At the end of the study, the checklist compliance rate throughout the full NCCU stays reached 97.11%. After controlling for SOFA score, age, sex and primary admitting diagnosis, the implementation of systematic checklists significantly correlated with a reduced LOS (ß=-0.15, 95% CI -0.24 to -0.06), reduced rate of any new infections (OR 0.59, 95% CI 0.40 to 0.87) and reduced urinary tract infections (UTIs) (OR 0.23, 95% CI 0.09 to 0.55). Propensity score and Euclidean distance matching yielded 382 and 338 pairs with excellent covariate balance. After matching, outcomes remained significant. DISCUSSION: The implementation of safety checklists in the NCCU proved feasible, easy to incorporate into the NCCU workflow, and a helpful tool to improve adherence to practice guidelines and quality of care measurements. Furthermore, our intervention resulted in a reduced NCCU-LOS, rate of new infections and rate of UTIs compared with propensity score and Euclidean distance matched historical controls.

Impact of systemic inflammatory response syndrome on acute ischemic stroke patients treated with mechanical thrombectomy.

AIM: Systemic inflammatory response syndrome (SIRS) has been associated with poor outcomes after acute ischemic stroke (AIS). The primary goal of this study was to determine whether SIRS status on admission correlated with functional outcomes in AIS treated with mechanical thrombectomy (MT). METHODS: Consecutive patients from September 2015 to April 2019 were retrospectively reviewed for SIRS on admission. SIRS was defined as the presence of ≥2 of the following: temperature < 36 °C or > 38 °C, heart rate > 90, respiratory rate > 20, and white blood cell count <4000/mm or > 12,000 mm. RESULTS: Of 202 patients, 188 met inclusion criteria. 49 patients (26%) had evidence of SIRS. Neither basic patient demographics nor standard stroke risk factors predicted the development of SIRS. However, presentation with SIRS was correlated with higher rates of death (odds ratio [OR], 2.6; 95% confidence interval [CI], 1.2-5.5) as well as lower rates of favorable functional outcomes at discharge (OR, 0.09; 95% CI, 0.02-0.40) and 3-month follow up (OR 0.12; 95% CI 0.03-0.43). These results remained significant even after adjustment for age, sex, baseline NIHSS, recanalization status, and prior co-morbidities. CONCLUSION: In our sample population, SIRS was associated with worse outcomes and higher rates of mortality in AIS patients treated with MT. Recognition of key risk factors can provide better prognostication and possible future therapeutic targets.

Hyperosmolar therapy: A century of treating cerebral edema.

Hyperosmolar therapy is a cornerstone for the management of elevated intracranial pressure in patients with devastating neurological injuries. Its discovery and use in various pathologies has become a valuable therapy in modern neurological critical care across the globe. Although hyperosmolar therapy is used routinely, the history of its origin is still elusive to many physicians. Understanding the basis of discovery and use of different hyperosmolar agents lends insight into the complex management of elevated intracranial pressure. There are very few practices in medicine which has stood the test of time. The discovery of hyperosmolar therapy has not only provided us a wealth of data for the management of intracranial hypertension but has also allowed us to develop new treatment strategies by improving our understanding of the molecular mechanisms of cerebral inflammation, blood-brain permeability, and cerebral edema in all modes of neuronal injury.

Risk of Stroke vs. Intracerebral Hemorrhage in Patients with Non-Valvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Comparing Dual vs. Triple Antithrombotic Therapy.

BACKGROUND: About 15% of patients with non-valvular atrial fibrillation might require percutaneous coronary interventions (PCIs) with stent placement to treat obstructive coronary artery disease. Dual antiplatelet therapy (DAPT) with acetylsalicylic acid (aspirin) and P2Y12 antagonist is recommended after PCI. Patients requiring DAPT also require treatment with oral anticoagulation for atrial fibrillation. We conducted a meta-analysis to identify the antithrombotic regimen associated with the lowest rate of bleeding and thromboembolic events in non-valvular atrial fibrillation after PCI. METHODS: We searched PubMed, Embase, Scopus and Cochrane databases to identify randomized trials that investigated the use of dual antiplatelet therapy and vitamin K antagonist and/or Non-vitamin K antagonist oral anticoagulants (NOAC) (triple antithrombotic therapy (TAT)) against single antiplatelet agent and NOAC (dual antithrombotic therapy (DAT)) in the setting of coronary artery disease (CAD) requiring PCI and non-valvular atrial fibrillation. Random-effect models were used to pool data. We used the I2 statistic to measure heterogeneity between trials. RESULTS: We found 4 randomized clinical trials (ENTRUST, AUGUSTUS, PIONEER, REDUAL) using different NOACs. Overall, 9241 patients (median age 70 years, 41.4% female, mean CHADS2VASC Score 3.5) were included. We excluded patients in the very low dose rivaroxaban group from the PIONEER AF-PCI trial and low dose dabigatran group from the REDUAL PCI trial as these are not available in the United States. Our metanalysis showed that dual therapy was associated with less risk of intracranial hemorrhage (RR 0.55, 95% CI 0.31-0.99; p = 0.045; I2 = 42%) and major bleeding (RR 0.66; 95% CI 0.55-0.79; p < 0.0001; I2 = 27%) as compared to triple therapy. Further risk of ischemic stroke (RR 0.94, 95% CI 0.63-1.39; p = 0.75; I2=0%), myocardial infarction (RR 1.18, 95% CI 0.94-1.47; p = 0.16; I2 = 0), or stent thrombosis (RR 0.50, 95% CI 0.93-2.41; p = 0.10; I2 = 0%) were unchanged. Similar findings were also noted on analysis of NOAC specific DAT vs VKA based TAT. CONCLUSIONS: The combination of an antiplatelet and NOACs (dual therapy) is associated with less risk of major bleeding and intracranial hemorrhage, with no significant difference in ischemic events (stroke myocardial infarction or stent thrombosis).

Blood pressure management after mechanical thrombectomy in stroke patients.

Endovascular treatment of acute ischemic stroke (AIS) and mechanical thrombectomy (MT) is proven as a safe and effective novel treatment for emergent large vessel occlusion in the anterior cerebral circulation. However, there are still many unanswered questions on peri and post-procedural management including blood pressure (BP) control. The current guidelines recommend maintaining BP <180/105 mmHg in the first 24 h after MT. However, recent studies suggest that maintaining BP levels at lower levels in the first 24 h after successful revascularization have been associated with favorable functional outcome, reduced mortality rate, and hemorrhagic complications. Not only absolute BP but also its variation in the first 24 h after MT have been associated with neurological outcomes. Evidence on the effect of BP variability (BPV) after MT in AIS even though limited, it does indicate the association of the higher BPV in the first 24 h after MT and poor functional outcomes in AIS. In this review, we will discuss the current literature on BP management in the first 24 h after MT and the impact of BPV in the first 24 h after MT.

Temporal Relationship between Hyponatremia and Development of Cerebral Vasospasm in Aneurysmal Subarachnoid Hemorrhage Patients: A Retrospective Observational Study.

BACKGROUND: Hyponatremia is a common complication after aneurysmal subarachnoid hemorrhage (aSAH). Previous studies have reported an association between hyponatremia and vasospasm, however whether hyponatremia directly contributes to the pathogenesis of cerebral vasospasm (CVS), or is a by-product is still unclear. The aim of this study was to explore an association between hyponatremia and CVS after aSAH, and evaluating the temporality of these 2 events. METHODS: A retrospective study of consecutive patients with aSAH admitted to the Baylor St. Luke's Medical center between January 2008 and December 2012 was conducted. Demographics, baseline characteristics, serum sodium levels, and evidence of vasospasm detected by transcranial Doppler, CT Angiogram, MR angiogram, and digital subtracted angiography were collected. Patients were dichotomized into a hyponatremic and a normonatremic group. CVS incidence and clinical outcome was compared between groups. Timing of CVS after initial hyponatremia episodes was recorded Results: One hundred and sixty 4 patients with aSAH were included. Hyponatremia was identified in 66 patients (40.2%) and CVS occurred in 71 subjects (43.2%). The incidence of CVS was higher in the hyponatremic group compared to the normonatremic group, 65.1 % versus 28.5%, respectively (P < .001). Hyponatremia preceded CVS by median 1.5 days suggesting a temporal trend. CONCLUSIONS: Our study shows a significant association between hyponatremia and CVS, with hyponatremia preceding CVS events. This retrospective finding denotes the need for larger prospective studies, aiming to clarify the temporal relationship of serum sodium levels and CVS.

Blood pressure variability and outcome after acute intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is life threatening neurologic event that results in significant rate of morbidity and mortality. Unfortunately, several randomized clinical trials aiming at limiting the hematoma expansion (HE) in the acute phase of ICH have not shown significant effects in improving the functional outcomes. Blood pressure variability (BPV) is common following ICH. High BPs have been associated with increased risk of bleeding and HE. Conversely, recurrent sudden decrease in BP promote perihematomal ischemia. However, it is still not clear weather BPV causes adverse prognosis following ICH or large ICHs cause fluctuations in BP. In the current review, we will discuss the mechanistic pathophysiology of BPV and the evidence regarding the role of BPV on the ICH outcomes.

Exploration of Multiparameter Hematoma 3D Image Analysis for Predicting Outcome After Intracerebral Hemorrhage.

BACKGROUND: Rapid diagnosis and proper management of intracerebral hemorrhage (ICH) play a crucial role in the outcome. Prediction of the outcome with a high degree of accuracy based on admission data including imaging information can potentially influence clinical decision-making practice. METHODS: We conducted a retrospective multicenter study of consecutive ICH patients admitted between 2012-2017. Medical history, admission data, and initial head computed tomography (CT) scan were collected. CT scans were semiautomatically segmented for hematoma volume, hematoma density histograms, and sphericity index (SI). Discharge unfavorable outcomes were defined as death or severe disability (modified Rankin Scores 4-6). We compared (1) hematoma volume alone; (2) multiparameter imaging data including hematoma volume, location, density heterogeneity, SI, and midline shift; and (3) multiparameter imaging data with clinical information available on admission for ICH outcome prediction. Multivariate analysis and predictive modeling were used to determine the significance of hematoma characteristics on the outcome. RESULTS: We included 430 subjects in this analysis. Models using automated hematoma segmentation showed incremental predictive accuracies for in-hospital mortality using hematoma volume only: area under the curve (AUC): 0.85 [0.76-0.93], multiparameter imaging data (hematoma volume, location, CT density, SI, and midline shift): AUC: 0.91 [0.86-0.97], and multiparameter imaging data plus clinical information on admission (Glasgow Coma Scale (GCS) score and age): AUC: 0.94 [0.89-0.99]. Similarly, severe disability predictive accuracy varied from AUC: 0.84 [0.76-0.93] for volume-only model to AUC: 0.88 [0.80-0.95] for imaging data models and AUC: 0.92 [0.86-0.98] for imaging plus clinical predictors. CONCLUSIONS: Multiparameter models combining imaging and admission clinical data show high accuracy for predicting discharge unfavorable outcome after ICH.

Brain Physiological Response and Adaptation During Spaceflight.

More than half of astronauts returning from long-duration missions on the International Space Station present with neuro-ocular structural and/or functional changes, including optic disc edema, optic nerve sheath distension, globe flattening, choroidal folds, or hyperopic shifts. This spaceflight-associated neuro-ocular syndrome (SANS) represents a major risk to future exploration class human spaceflight missions, including Mars missions. Although the exact pathophysiology of SANS is unknown, evidence thus far suggests that an increase in intracranial pressure (ICP) relative to the upright position on Earth, which is due to the loss of hydrostatic pressure gradients in space, may play a leading role. This review focuses on brain physiology in the spaceflight environment, specifically on how spaceflight may affect ICP and related indicators of cranial compliance, potential factors related to the development of SANS, and findings from spaceflight as well as ground-based spaceflight analog research studies.

Common Data Element for Unruptured Intracranial Aneurysm and Subarachnoid Hemorrhage: Recommendations from Assessments and Clinical Examination Workgroup/Subcommittee.

BACKGROUND: Clinical studies of subarachnoid hemorrhage (SAH) and unruptured cerebral aneurysms lack uniformity in terms of variables used for assessments and clinical examination of patients which has led to difficulty in comparing studies and performing meta-analyses. The overall goal of the National Institute of Health/National Institute of Neurological Disorders and Stroke Unruptured Intracranial Aneurysms (UIA) and subarachnoid hemorrhage (SAH) Common Data Elements (CDE) Project was to provide common definitions and terminology for future unruptured intracranial aneurysm and SAH research. METHODS: This paper summarizes the recommendations of the subcommittee on SAH Assessments and Clinical Examination. The subcommittee consisted of an international and multidisciplinary panel of experts in UIA and SAH. Consensus recommendations were developed by reviewing previously published CDEs for other neurological diseases including traumatic brain injury, epilepsy and stroke, and the SAH literature. Recommendations for CDEs were classified by priority into "core," "supplemental-highly recommended," "supplemental" and "exploratory." RESULTS: We identified 248 variables for Assessments and Clinical Examination. Only the World Federation of Neurological Societies grading scale was classified as "Core." The Glasgow Coma Scale was classified as "Supplemental-Highly Recommended." All other Assessments and Clinical Examination variables were categorized as "Supplemental." CONCLUSION: The recommended Assessments and Clinical Examination variables have been collated from a large number of potentially useful scales, history, clinical presentation, laboratory, and other tests. We hope that adherence to these recommendations will facilitate the comparison of results across studies and meta-analyses of individual patient data.

Serum magnesium level and hematoma expansion in patients with intracerebral hemorrhage.

Spontaneous intracerebral hemorrhage (ICH) is a devastating subtype of stroke that results in significant rates of mortality and morbidities. The initial hematoma volume, hematoma expansion (HE), blood pressure (BP), and coagulopathy are considered strong predictors of clinical outcomes and mortality. Low serum magnesium (Mg++) levels have been shown to be associated with larger initial hematoma and greater HE. Coagulopathy, platelet dysfunction, high BP, and increased inflammatory response might form the mechanistic link between low serum Mg++ levels, larger hematoma size and greater HE. However, randomized clinical trials administering intravenous Mg++ have shown no benefit over placebo in ICH patients. The confounding effect of hypocalcemia and a delay in Mg++ trafficking across the blood-brain barrier might explain the futile results for intravenous Mg++ therapy. In the current review, we will discuss the evidence regarding the possible role of low serum Mg++ level on HE in acute ICH.

Full-Dose Thrombolysis for a Right Middle Cerebral Artery Stroke after an Acute Aortic Dissection.

Intravenous recombinant tissue plasminogen activator (IV r-tpa) is the standard of care for patients suffering from neurological deficits due to an acute ischemic stroke within 4.5 hours in the absence of intracranial hemorrhage. We report a case of a patient with an acute right middle cerebral artery stroke due to an acute aortic dissection (Stanford Type A) who was treated with full dose IV r-tpa resulting in a good outcome.

Regional Intervention of Stroke Care to Increase Thrombolytic Therapy for Acute Ischemic Stroke.

Background and Purpose- The aims of this study were to investigate the effect of an intervention to unblind data on r-tPA (recombinant tissue-type plasminogen activator) administration and sharing data with chief executive officers of participating hospitals, on r-tPA administration rates postintervention and on potential healthcare cost savings implemented at 26 Southeast Texas Regional Advisory Council hospitals. Methods- Retrospective analysis of prospective data on thrombolytic therapy from 26 Southeast Texas Regional Advisory Council hospitals, collected between April 2014 and June 2016. The control (blinded) period (Q2-2014 to Q2-2015) was followed by unblinding (Q3-2015). Results- Intervention was associated with 21.1% increase in r-tPA administration rates, with 38.5% increase in r-tPA administration with door-to-needle time ≤60 minutes. An absolute increase in r-tPA administration of 2.1% was seen with an average lifetime cost savings of $3.6 million. Conclusions- Transparent regional data sharing was associated with improved r-tPA administration and healthcare cost savings.

Real-time Noninvasive Monitoring of Intracranial Fluid Shifts During Dialysis Using Volumetric Integral Phase-Shift Spectroscopy (VIPS): A Proof-of-Concept Study.

BACKGROUND: Cerebral edema, which is associated with increased intracranial fluid, is often a complication of many acute neurological conditions. There is currently no accepted method for real-time monitoring of intracranial fluid volume at the bedside. We evaluated a novel noninvasive technique called "Volumetric Integral Phase-shift Spectroscopy (VIPS)" for detecting intracranial fluid shifts during hemodialysis. METHODS: Subjects receiving scheduled hemodialysis for end-stage renal disease and without a history of major neurological conditions were enrolled. VIPS monitoring was performed during hemodialysis. Serum osmolarity, electrolytes, and cognitive function with mini-mental state examination (MMSE) were assessed. RESULTS: Twenty-one monitoring sessions from 14 subjects (4 women), mean group age 50 (SD 12.6), were analyzed. The serum osmolarity decreased by a mean of 6.4 mOsm/L (SD 6.6) from pre- to post-dialysis and correlated with an increase in the VIPS edema index (E-Dex) of 9.7% (SD 12.9) (Pearson's correlation r = 0.46, p = 0.037). Of the individual determinants of serum osmolarity, changes in serum sodium level correlated best with the VIPS edema index (Pearson's correlation, r = 0.46, p = 0.034). MMSE scores did not change from pre- to post-dialysis. CONCLUSIONS: We detected an increase in the VIPS edema index during hemodialysis that correlated with decreased serum osmolarity, mainly reflected by changes in serum sodium suggesting shifts in intracranial fluids.

Secondary Stroke Prevention in Nonvalvular Atrial Fibrillation.

Approximately 750,000 US adults per year experience a stroke. On average, the annual risk for future ischemic stroke (secondary stroke) after an initial ischemic stroke or transient ischemic attack is approximately 3% to 4%. Cardioembolic strokes account for 20% to 25% of all strokes, with nonvalvular atrial fibrillation (NVAF) considered one of the main sources of embolism; this explains up to half of all cardioembolic strokes. We present the risk factors for stroke in NVAF, risk stratification, a diagnosis of NVAF, and treatment and prevention of stroke in NVAF. We reviewed the literature by performing a PubMed search of articles focusing on secondary stroke prevention in NVAF. This review examines the findings of major clinical trials and society guidelines for secondary stroke prevention in NVAF and presents a cost-effectiveness analysis.