Impact of Continuous Infusion Ketamine Compared to Continuous Infusion Benzodiazepines on Delirium in the Intensive Care Unit.

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods: In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines.

Predicting Hospital Survival in Patients Admitted to ICU with Pulmonary Embolism.

OBJECTIVE: The Pulmonary Embolism Severity Index (PESI) and simplified PESI (sPESI) predict mortality for patients with PE. We compared PESI/sPESI to the Acute Physiology and Chronic Health Evaluation IV (APACHE-IV) in predicting mortality in patients with PE admitted to the intensive care unit (ICU). Additionally, we assessed the performance of a novel ICU-sPESI score created by adding three clinical variables associated with acuity of PE presentation (intubation, confusion [altered mental status], use of vasoactive infusions) to sPESI. MATERIALS AND METHODS: Using the eICU Collaborative Research Database from 2014 to 2015, we conducted a large retrospective cohort study of adult patients admitted to the ICU with a primary diagnosis of PE. We calculated APACHE-IV, PESI, sPESI, and ICU-sPESI scores and compared their performance for predicting in-hospital mortality using area under the receiver operating characteristic (AUROC) curve. Score thresholds for >99% negative predictive values (NPV) were calculated for each score. Survival was estimated using the Kaplan-Meier method. RESULTS: We included 1424 PE cases. In-hospital mortality was 6.3% [95% CI: 5.1%-7.6%]. AUROC for APACHE-IV, PESI, and sPESI were 0.870, 0.848, and 0.777, respectively. APACHE-IV and PESI outperformed sPESI (P < 0.01 for both comparisons), while APACHE-IV and PESI demonstrated similar performance (P = 0.322). The ICU-sPESI performance was similar to APACHE-IV and PESI (AUROC = 0.847; AUROC comparison: APACHE-IV vs ICU-sPESI: P = 0.396; PESI vs ICU-sPESI: P = 0.945). Hospital mortality for ICU-sPESI scores 0-2 was 1.1%, and for scores 3, 4, 5, 6, and ≥7 was 8.6%, 11.7%, 29.2%, 37.5%, and 76.9%, respectively. Score thresholds for >99% NPV were ≤48 for APACHE-IV, ≤115 for PESI, and 0 points for sPESI and ICU-sPESI. CONCLUSIONS: By accounting for severity of PE presentation, our newly proposed ICU-sPESI score provided improved PE mortality prediction compared to the original sPESI score and offered excellent discrimination of mortality risk.

Optical Coherence Tomography Angiography Retinal Imaging Associations With Burden of Small Vessel Disease and Amyloid Positivity in the Brain.

BACKGROUND: Alzheimer disease (AD) and other dementias are associated with vascular changes and amyloid deposition, which may be reflected as density changes in the retinal capillaries. These changes may can be directly visualized and quantified with optical coherence tomography angiography (OCTA), making OCTA a potential noninvasive preclinical biomarker of small vessel disease and amyloid positivity. Our objective was to investigate the feasibility of retinal imaging metrics as noninvasive biomarkers of small vessel disease and amyloid positivity in the brain. METHODS: We investigated associations between OCTA and neuroimaging and cognitive metrics in 41 participants without dementia from the Mayo Clinic Study of Aging and Alzheimer's Disease Research Center. OCTA metrics included superficial, deep, and full retina capillary density of the fovea, parafovea, and macula as well as the area of the foveal avascular zone (FAZ). Neuroimaging metrics included a high burden of white matter hyperintensity (WMH), presence of cerebral microbleeds (CMB), lacunar infarcts, and amyloid positivity as evidenced on positron emission tomography (PET), whereas cognitive metrics included mini-mental status examination (MMSE) score. We performed generalized estimating equations to account for measurements in each eye while controlling for age and sex to estimate associations between OCTA metrics and neuroimaging and cognitive scores. RESULTS: Associations between OCTA and neuroimaging metrics were restricted to the fovea. OCTA showed decreased capillary density with high burden of WMH in both the superficial (P = 0.003), deep (P = 0.004), and full retina (P = 0.01) in the fovea but not the parafovea or whole macula. Similarly, participants with amyloid PET positivity had significantly decreased capillary density in the superficial fovea (P = 0.027) and deep fovea (P = 0.03) but higher density in the superficial parafovea (P = 0.038). Participants with amyloid PET positivity also had a significantly larger FAZ (P = 0.031), whereas in those with high WMH burden the difference did not reach statistical significance (P = 0.075). There was also a positive association between MMSE and capillary density of the full retina within the fovea (P = 0.037) and in the superficial parafovea (P = 0.046). No associations were found between OCTA metrics and presence of CMB or presence of lacunar infarcts. CONCLUSION: The associations of lower foveal capillary density with cerebral WMH and amyloid positivity suggest that further research is warranted to evaluate for shared mechanisms of disease between small vessel disease and AD pathologies.

Machine learning prediction of hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the United States.

BACKGROUND AND PURPOSE: Predicting patient recovery and discharge disposition following mechanical thrombectomy remains a challenge in patients with ischemic stroke. Machine learning offers a promising prognostication approach assisting in personalized post-thrombectomy care plans and resource allocation. As a large national database, National Inpatient Sample (NIS), contain valuable insights amenable to data-mining. The study aimed to develop and evaluate ML models predicting hospital discharge disposition with a focus on demographic, socioeconomic and hospital characteristics. MATERIALS AND METHODS: The NIS dataset (2006-2019) was used, including 4956 patients diagnosed with ischemic stroke who underwent thrombectomy. Demographics, hospital characteristics, and Elixhauser comorbidity indices were recorded. Feature extraction, processing, and selection were performed using Python, with Maximum Relevance - Minimum Redundancy (MRMR) applied for dimensionality reduction. ML models were developed and benchmarked prior to interpretation of the best model using Shapley Additive exPlanations (SHAP). RESULTS: The multilayer perceptron model outperformed others and achieved an AUROC of 0.81, accuracy of 77 %, F1-score of 0.48, precision of 0.64, and recall of 0.54. SHAP analysis identified the most important features for predicting discharge disposition as dysphagia and dysarthria, NIHSS, age, primary payer (Medicare), cerebral edema, fluid and electrolyte disorders, complicated hypertension, primary payer (private insurance), intracranial hemorrhage, and thrombectomy alone. CONCLUSION: Machine learning modeling of NIS database shows potential in predicting hospital discharge disposition for inpatients with acute ischemic stroke following mechanical thrombectomy in the NIS database. Insights gained from SHAP interpretation can inform targeted interventions and care plans, ultimately enhancing patient outcomes and resource allocation.

The impact of pre-stroke metformin use on clinical outcomes after acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVES: Stroke is a leading cause of mortality and disability globally, with limited treatment options available for acute ischemic stroke (AIS) patients. Type 2 diabetes mellitus (T2DM) is not only widespread but also a known risk factor for stroke. Our meta-analysis aims to assess the influence of pre-stroke metformin use on the clinical outcomes in AIS patients with T2DM. MATERIALS AND METHODS: We conducted this study following PRISMA guidelines, searching the following databases: Medline, Embase, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials up to February 29, 2024. All studies providing separate data on AIS patients using metformin were included, and statistical analysis was conducted using R software to pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: Out of 1051 studies, 7 met the inclusion criteria for our meta-analysis with a total of 11589 diabetic patients, including 5445 patients taking metformin and 6144 diabetic patients in the non-metformin group. Compared to the non-metformin group, the metformin group had a significantly higher rate of mRS 0-2 score at discharge (OR 1.56; 95% CI 1.25:1.95; p=< 0.01) and a lower rate of 90-day mortality (OR 0.51; 95% CI 0.42:0.61; p=< 0.01), with no significant difference in sICH (OR 0.88; 95% CI 0.47:1.64; p= 0.68) between the two groups. CONCLUSIONS: Our meta-analysis demonstrated that pre-stroke metformin use is associated with higher functional independence and lower mortality in AIS patients with T2DM.

2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage: A Guideline From the American Heart Association/American Stroke Association.

AIM: The "2023 Guideline for the Management of Patients With Aneurysmal Subarachnoid Hemorrhage" replaces the 2012 "Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage." The 2023 guideline is intended to provide patient-centric recommendations for clinicians to prevent, diagnose, and manage patients with aneurysmal subarachnoid hemorrhage. METHODS: A comprehensive search for literature published since the 2012 guideline, derived from research principally involving human subjects, published in English, and indexed in MEDLINE, PubMed, Cochrane Library, and other selected databases relevant to this guideline, was conducted between March 2022 and June 2022. In addition, the guideline writing group reviewed documents on related subject matter previously published by the American Heart Association. Newer studies published between July 2022 and November 2022 that affected recommendation content, Class of Recommendation, or Level of Evidence were included if appropriate. Structure: Aneurysmal subarachnoid hemorrhage is a significant global public health threat and a severely morbid and often deadly condition. The 2023 aneurysmal subarachnoid hemorrhage guideline provides recommendations based on current evidence for the treatment of these patients. The recommendations present an evidence-based approach to preventing, diagnosing, and managing patients with aneurysmal subarachnoid hemorrhage, with the intent to improve quality of care and align with patients' and their families' and caregivers' interests. Many recommendations from the previous aneurysmal subarachnoid hemorrhage guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Artificial intelligence-guided screening for atrial fibrillation using electrocardiogram during sinus rhythm: a prospective non-randomised interventional trial.

BACKGROUND: Previous atrial fibrillation screening trials have highlighted the need for more targeted approaches. We did a pragmatic study to evaluate the effectiveness of an artificial intelligence (AI) algorithm-guided targeted screening approach for identifying previously unrecognised atrial fibrillation. METHODS: For this non-randomised interventional trial, we prospectively recruited patients with stroke risk factors but with no known atrial fibrillation who had an electrocardiogram (ECG) done in routine practice. Participants wore a continuous ambulatory heart rhythm monitor for up to 30 days, with the data transmitted in near real time through a cellular connection. The AI algorithm was applied to the ECGs to divide patients into high-risk or low-risk groups. The primary outcome was newly diagnosed atrial fibrillation. In a secondary analysis, trial participants were propensity-score matched (1:1) to individuals from the eligible but unenrolled population who served as real-world controls. This study is registered with ClinicalTrials.gov, NCT04208971. FINDINGS: 1003 patients with a mean age of 74 years (SD 8·8) from 40 US states completed the study. Over a mean 22·3 days of continuous monitoring, atrial fibrillation was detected in six (1·6%) of 370 patients with low risk and 48 (7·6%) of 633 with high risk (odds ratio 4·98, 95% CI 2·11-11·75, p=0·0002). Compared with usual care, AI-guided screening was associated with increased detection of atrial fibrillation (high-risk group: 3·6% [95% CI 2·3-5·4] with usual care vs 10·6% [8·3-13·2] with AI-guided screening, p<0·0001; low-risk group: 0·9% vs 2·4%, p=0·12) over a median follow-up of 9·9 months (IQR 7·1-11·0). INTERPRETATION: An AI-guided targeted screening approach that leverages existing clinical data increased the yield for atrial fibrillation detection and could improve the effectiveness of atrial fibrillation screening. FUNDING: Mayo Clinic Robert D and Patricia E Kern Center for the Science of Health Care Delivery.

Developing DELPHI expert consensus rules for a digital twin model of acute stroke care in the neuro critical care unit.

INTRODUCTION: Digital twins, a form of artificial intelligence, are virtual representations of the physical world. In the past 20 years, digital twins have been utilized to track wind turbines' operations, monitor spacecraft's status, and even create a model of the Earth for climate research. While digital twins hold much promise for the neurocritical care unit, the question remains on how to best establish the rules that govern these models. This model will expand on our group's existing digital twin model for the treatment of sepsis. METHODS: The authors of this project collaborated to create a Direct Acyclic Graph (DAG) and an initial series of 20 DELPHI statements, each with six accompanying sub-statements that captured the pathophysiology surrounding the management of acute ischemic strokes in the practice of Neurocritical Care (NCC). Agreement from a panel of 18 experts in the field of NCC was collected through a 7-point Likert scale with consensus defined a-priori by ≥ 80% selection of a 6 ("agree") or 7 ("strongly agree"). The endpoint of the study was defined as the completion of three separate rounds of DELPHI consensus. DELPHI statements that had met consensus would not be included in subsequent rounds of DELPHI consensus. The authors refined DELPHI statements that did not reach consensus with the guidance of de-identified expert comments for subsequent rounds of DELPHI. All DELPHI statements that reached consensus by the end of three rounds of DELPHI consensus would go on to be used to inform the construction of the digital twin model. RESULTS: After the completion of three rounds of DELPHI, 93 (77.5%) statements reached consensus, 11 (9.2%) statements were excluded, and 16 (13.3%) statements did not reach a consensus of the original 120 DELPHI statements. CONCLUSION: This descriptive study demonstrates the use of the DELPHI process to generate consensus among experts and establish a set of rules for the development of a digital twin model for use in the neurologic ICU. Compared to associative models of AI, which develop rules based on finding associations in datasets, digital twin AI created by the DELPHI process are easily interpretable models based on a current understanding of underlying physiology.

A clinical primer for the glymphatic system.

The complex and dynamic system of fluid flow through the perivascular and interstitial spaces of the CNS has new-found implications for neurological diseases. CSF movement throughout the CNS parenchyma is more dynamic than could be explained via passive diffusion mechanisms alone. Indeed, a semistructured glial-lymphatic (glymphatic) system of astrocyte-supported extracellular perivascular channels serves to directionally channel extracellular fluid, clearing metabolites and peptides to optimize neurological function. Clinical studies of the glymphatic network have to date proven challenging, with most data gleaned from rodent models and post-mortem investigations. However, increasing evidence suggests that disordered glymphatic function contributes to the pathophysiology of CNS ageing, neurodegenerative disease and CNS injuries, as well as normal pressure hydrocephalus. Unlocking such pathophysiology could provide important avenues towards novel therapeutics. We here provide a multidisciplinary overview of glymphatics and critically review accumulating evidence regarding its structure, function and hypothesized relevance to neurological disease. We highlight emerging technologies of relevance to the longitudinal evaluation of glymphatic function in health and disease. Finally, we discuss the translational opportunities and challenges of studying glymphatic science.

Urine Output and Mortality in Patients Resuscitated from out of Hospital Cardiac Arrest.

BACKGROUND: Limited data exist regarding urine output (UO) as a prognostic marker in out-of-hospital-cardiac-arrest (OHCA) survivors undergoing targeted temperature management (TTM). METHODS: We included 247 comatose adult patients who underwent TTM after OHCA between 2007 and 2017, excluding patients with end-stage renal disease. Three groups were defined based on mean hourly UO during the first 24 h: Group 1 (<0.5 mL/kg/h, n = 73), Group 2 (0.5-1 mL/kg/h, n = 81) and Group 3 (>1 mL/kg/h, n = 93). Serum creatinine was used to classify acute kidney injury (AKI). The primary and secondary outcomes respectively were in-hospital mortality and favorable neurological outcome at hospital discharge (modified Rankin Scale [mRS]<3). RESULTS: In-hospital mortality decreased incrementally as UO increased (adjusted OR 0.9 per 0.1 mL/kg/h higher; p = 0.002). UO < 0.5 mL/kg/h was strongly associated with higher in-hospital mortality (adjusted OR 4.2 [1.6-10.8], p = 0.003) and less favorable neurological outcomes (adjusted OR 0.4 [0.2-0.8], p = 0.007). Even among patients without AKI, lower UO portended higher mortality (40% vs 15% vs 9% for UO groups 1, 2, and 3 respectively, p < 0.001). CONCLUSION: Higher UO is incrementally associated with lower in-hospital mortality and better neurological outcomes. Oliguria may be a more sensitive early prognostic marker than creatinine-based AKI after OHCA.

Safety of peripheral 3% hypertonic saline bolus administration for neurologic emergency.

BACKGROUND/OBJECTIVE: Hypertonic sodium chloride (HTS) is used for emergent treatment of acute cerebral edema and other neurologic emergencies. Central access is not commonly available in emergent situations and 3% HTS is utilized peripherally. Many studies have shown the safety of its administration at rates up to 75 mL/h, but there is a lack of data to establish the safety of peripherally administered, rapid bolus dosing in emergent situations. The objective of this study is to describe the safety of rapid, peripherally administered (≥ 250 mL/h) 3% HTS for neurologic emergencies. METHODS: This is a retrospective, cohort study including adult patients receiving 3% HTS via a peripheral IV site for elevated intracranial pressure, cerebral edema, or other neurological emergencies at a rate of at least 250 m/h between May 5, 2018 - September 30, 2021. Patients were excluded if they simultaneously received another hypertonic saline fluid. Baseline characteristics collected included HTS dose, rate and site of administration, indication for use and patient demographics. The primary safety outcome was incidence of extravasation and phlebitis within one hour of HTS administration. RESULTS: There were 206 patients receiving 3% HTS who were screened, and 37 patients met inclusion criteria. The most common reason for exclusion was administration at a rate < 250 m/h. The median age was 60 (IQR 45, 72) with 51.4% being male. The most common indications for HTS were traumatic brain injury (45.9%) and intracranial hemorrhage (37.8%). The most common administration location was the emergency department (78.4%). The median IV-gauge (n = 29) was 18 (IQR 18, 20), with the most common placement site being antecubital (48.6%). The median dose of HTS was 250 mL (IQR 250, 350), with a median administration rate of 760 mL/h (IQR 500, 999). There were no episodes of extravasation or phlebitis noted. CONCLUSIONS: Rapid, peripheral administration of 3% HTS boluses is a safe alternative for treatment of neurologic emergencies. Administration at rates up to 999 mL/h did not result in extravasation or phlebitis.

Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding.

BACKGROUND: Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. METHODS: This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018-2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. RESULTS: Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. CONCLUSION: In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.

Prevention and Correction of Dysnatremia After Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Dysnatremia occurs commonly in patients with aneurysmal subarachnoid hemorrhage (aSAH). The mechanisms for development of sodium dyshomeostasis are complex, including the cerebral salt-wasting syndrome, the syndrome of inappropriate secretion of antidiuretic hormone, diabetes insipidus. Iatrogenic occurrence of altered sodium levels plays a role, as sodium homeostasis is tightly linked to fluid and volume management. METHODS: Narrative review of the literature. RESULTS: Many studies have aimed to identify factors predictive of the development of dysnatremia, but data on associations between dysnatremia and demographic and clinical variables are variable. Furthermore, although a clear relationship between serum sodium serum concentrations and outcomes has not been established-poor outcomes have been associated with both hyponatremia and hypernatremia in the immediate period following aSAH and set the basis for seeking interventions to correct dysnatremia. While sodium supplementation and mineralocorticoids are frequently administered to prevent or counter natriuresis and hyponatremia, evidence to date is insufficient to gauge the effect of such treatment on outcomes. CONCLUSIONS: In this article, we reviewed available data and provide a practical interpretation of these data as a complement to the newly issued guidelines for management of aSAH. Gaps in knowledge and future directions are discussed.

Liberation from Mechanical Ventilation and Tracheostomy Practice in Traumatic Brain Injury.

Liberating patients with severe traumatic brain injury (TBI) from mechanical ventilation is often a challenging task. These patients frequently require prolonged ventilation and have persistent alterations in the level and content of consciousness. Questions about their ability to protect their airway are common. Pulmonary complications and copious respiratory secretions are also very prevalent. Thus, it is hardly surprising that rates of extubation failure are high. This is a major problem because extubation failure is associated with a host of poor outcome measures. When the safety of an extubation attempt is uncertain, direct tracheostomy is favored by some, but there is no evidence that this practice leads to better outcomes. Current knowledge is insufficient to reliably predict extubation outcomes in TBI, and practices vary substantially across trauma centers. Yet observational studies provide relevant information that must be weighted when considering the decision to attempt extubation in patients with head injury. This review discusses available evidence on liberation from mechanical ventilation in TBI, proposes priorities for future research, and offers practical advice to guide decisions at the bedside.

Perfusion Deficits in Patients with Posterior Reversible Encephalopathy Syndrome: a Retrospective, Two-Center Study.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is manifested by acute neurological symptoms in patients with varied predisposing factors and characteristic findings on brain imaging. Cerebrovascular autoregulation is thought to be altered in PRES. However, it remains unclear whether cerebral hypoperfusion or hyperperfusion is the initiating event. We aimed to describe the brain perfusion status in untreated patients with PRES. METHODS: Patients with PRES who underwent cerebral perfusion studies on presentation were retrospectively identified from (1) a prospective database of patients with PRES admitted to Saint Mary's Hospital, Mayo Clinic, Rochester from January 2005 to December 2021 and (2) University of Nebraska Medical Center electronic database from January 2010 to December 2021. Demographics, past medical history, presenting symptoms, cause of PRES, and clinical outcomes were recorded. Brain imaging studies were reviewed. We recorded the location of brain lesions, the time from symptoms onset to perfusion study, blood pressure at the time of the perfusion study, and blood pressure lowering treatments. RESULTS: Five patients (four women, median age 66 years) were included. Causes of PRES were acute hypertension (n = 3), perioperative blood pressure fluctuations, and treatment with pazopanib. Four patients had chronic hypertension. Presenting symptoms were encephalopathy (n = 5), focal neurological symptoms (n = 4), and seizures (n = 2). All patients underwent computed tomography (CT) perfusion performed within 12 h of symptoms onset. All but one patient was hypertensive at the time of CT perfusion. Scans showed diffuse cerebral hypoperfusion, more pronounced in the corona radiata and areas with brain edema. No patient had critical cerebral ischemia or arterial vasoconstriction on CT angiogram. CONCLUSIONS: Patients with PRES can have cerebral hypoperfusion despite severe hypertension. A perfusion study in the acute setting may be helpful to better understand the perfusion status and guide blood pressure treatment.

Clinical Characteristics, Imaging Findings, and Outcomes of Cerebral Air Embolism.

BACKGROUND: Arterial cerebral air embolism (CAE) is an uncommon but potentially catastrophic event. Patients can present with focal neurologic deficits, seizures, or coma. They may be treated with hyperbaric oxygen therapy. We review the causes, radiographic and clinical characteristics, and outcomes of patients with CAE. METHODS: We performed a retrospective chart review via an existing institutional database at Mayo Clinic to identify patients with arterial CAE. Demographic data, clinical characteristics, and diagnostic studies were extracted and classified on predefined criteria of diagnostic confidence, and descriptive and univariate analysis was completed. RESULTS: Fifteen patients met criteria for inclusion in our study. Most presented with focal deficits (80%) and/or coma (53%). Seven patients (47%) had seizures, including status epilepticus in one (7%). Five presented with increased muscle tone at the time of the event (33%). Computed tomography (CT) imaging was insensitive for the detection of CAE, only identifying free air in 4 of 13 who underwent this study. When obtained, magnetic resonance imaging typically showed multifocal areas of restricted diffusion. Six patients (40%) were treated with hyperbaric oxygen therapy. Age, Glasgow Coma Scale score at nadir, and use of hyperbaric oxygen therapy were not associated with functional outcome at 1 year in our cohort. Twenty-six percent of patients had a modified Rankin scale score of 0 one year after the event, and functional improvement over time was common after discharge. CONCLUSIONS: A high index of clinical suspicion is needed to identify patients with CAE because of low sensitivity of free air on CT imaging and nonspecific clinical presentation. Acute alteration of consciousness, seizures, and focal signs occur frequently. Because improvement over time is possible even among patients with severe presentation, early prognostication should be approached with caution.

Association of Blood Pressure Variability with Delirium in Patients with Critical Illness.

BACKGROUND: The objective was to examine the association of blood pressure variability (BPV) during the first 24 h after intensive care unit admission with the likelihood of delirium and depressed alertness without delirium ("depressed alertness"). METHODS: This retrospective, observational, cohort study included all consecutive adult patients admitted to an intensive care unit at Mayo Clinic, Rochester, Minnesota, from July 1, 2004, through October 31, 2015. The primary outcomes were delirium and delirium-free days, and the secondary outcomes included depressed alertness and depressed alertness-free days. Logistic regression was performed to determine the association of BPV with delirium and depressed alertness. Proportional odds regression was used to assess the association of BPV with delirium-free days and depressed alertness-free days. RESULTS: Among 66,549 intensive care unit admissions, delirium was documented in 20.2% and depressed alertness was documented in 24.4%. Preserved cognition was documented in 55.4% of intensive care unit admissions. Increased systolic and diastolic BPV was associated with an increased odds of delirium and depressed alertness. The magnitude of the association per 5-mm Hg increase in systolic average real variability (the average of absolute value of changes between consecutive systolic blood pressure readings) was greater for delirium (odds ratio 1.34; 95% confidence interval 1.29-1.40; P < 0.001) than for depressed alertness (odds ratio 1.06; 95% confidence interval 1.02-1.10; P = 0.004). Increased systolic and diastolic BPV was associated with fewer delirium-free days but not with depressed alertness-free days. CONCLUSIONS: BPV in the first 24 h after intensive care unit admission is associated with an increased likelihood of delirium and fewer delirium-free days.

Guidelines for the Neurocritical Care Management of Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: The neurointensive care management of patients with aneurysmal subarachnoid hemorrhage (aSAH) is one of the most critical components contributing to short-term and long-term patient outcomes. Previous recommendations for the medical management of aSAH comprehensively summarized the evidence based on consensus conference held in 2011. In this report, we provide updated recommendations based on appraisal of the literature using the Grading of Recommendations Assessment, Development, and Evaluation methodology. METHODS: The Population/Intervention/Comparator/Outcome (PICO) questions relevant to the medical management of aSAH were prioritized by consensus from the panel members. The panel used a custom-designed survey instrument to prioritize clinically relevant outcomes specific to each PICO question. To be included, the study design qualifying criteria were as follows: prospective randomized controlled trials (RCTs), prospective or retrospective observational studies, case-control studies, case series with a sample larger than 20 patients, meta-analyses, restricted to human study participants. Panel members first screened titles and abstracts, and subsequently full text review of selected reports. Data were abstracted in duplicate from reports meeting inclusion criteria. Panelists used the Grading of Recommendations Assessment, Development, and Evaluation Risk of Bias tool for assessment of RCTs and the "Risk of Bias In Nonrandomized Studies - of Interventions" tool for assessment of observational studies. The summary of the evidence for each PICO was presented to the full panel, and then the panel voted on the recommendations. RESULTS: The initial search retrieved 15,107 unique publications, and 74 were included for data abstraction. Several RCTs were conducted to test pharmacological interventions, and we found that the quality of evidence for nonpharmacological questions was consistently poor. Five PICO questions were supported by strong recommendations, one PICO question was supported by conditional recommendations, and six PICO questions did not have sufficient evidence to provide a recommendation. CONCLUSIONS: These guidelines provide recommendations for or against interventions proven to be effective, ineffective, or harmful in the medical management of patients with aSAH based on a rigorous review of the available literature. They also serve to highlight gaps in knowledge that should guide future research priorities. Despite improvements in the outcomes of patients with aSAH over time, many important clinical questions remain unanswered.

Effects of Tranexamic Acid in Patients with Subarachnoid Hemorrhage in Brazil: A Prospective Observational Study with Propensity Score Analysis.

BACKGROUND: Rebleeding from a ruptured aneurysm increases the risk of unfavorable outcomes after subarachnoid hemorrhage (SAH) and is prevented by early aneurysm occlusion. The role of antifibrinolytics before aneurysm obliteration remains controversial. We investigated the effects of tranexamic acid on long-term functional outcomes of patients with aneurysmal SAH (aSAH). METHODS: This was a single-center, prospective, observational study conducted in a high-volume tertiary hospital in a middle-income country from December 2016 to February 2020. We included all consecutive patients with aSAH who either received or did not receive tranexamic acid (TXA) treatment. Multivariate logistic regression analysis using propensity score was used to evaluate the association of TXA use with long-term functional outcomes, measured by the modified Rankin Scale (mRS) at 6 months. RESULTS: A total of 230 patients with aSAH were analyzed. The median (interquartile range) age was 55 (46-63) years, 72% were women, 75% presented with good clinical grade (World Federation of Neurological Surgeons grade 1-3), and 83% had a Fisher scale of 3 or 4. Around 80% of patients were admitted up to 72 h from ictus. The aneurysm occlusion method was surgical clipping in 80% of the patients. A total of 129 patients (56%) received TXA. In multivariable logistic regression using inverse probability treatment weighting, the long-term rate of unfavorable outcomes (modified Rankin scale 4-6) was the same in the TXA and non-TXA groups (61 [48%] in TXA group vs. 33 [33%] in non-TXA group; odds ratio [OR] 1.39, 95% confidence interval [CI] 0.67-2.92; p = 0.377). The TXA group had higher in-hospital mortality (33 vs. 11% in non-TXA group; OR 4.13, 95% CI 1.55-12.53, p = 0.007). There were no differences between the groups concerning intensive care unit length of stay (16 ± 11.22 days in TXA group vs. 14 ± 9.24 days in non-TXA group; p = 0.2) or hospital (23 ± 13.35 days in TXA group vs. 22 ± 13.36 days in non-TXA group; p = 0.9). There was no difference in the rates of rebleeding (7.8% in TXA group vs. 8.9% in non-TXA group; p = 0.31) or delayed cerebral ischemia (27% in TXA group vs. 19% in non-TXA group; p = 0.14). For the propensity-matched analysis, 128 individuals were selected (64 in TXA group and 64 in non-TXA group), and the rates of unfavorable outcomes at 6 months were also similar between groups (45% in TXA group and 36% in non-TXA group; OR 1.22, 95% CI 0.51-2.89; p = 0.655). CONCLUSIONS: Our findings in a cohort with delayed aneurysm treatment reinforce previous data that TXA use before aneurysm occlusion does not improve functional outcomes in aSAH.

Differences between males and females following endovascular therapy for stroke: A systematic review and meta-analysis.

BACKGROUND: Endovascular therapy (EVT) represents the standard of care for eligible patients with acute ischemic stroke (AIS) and large vessel occlusion. To better understand differences in baseline characteristics and outcomes between males and females following EVT, we conducted a systematic review and meta-analysis. METHODS: We identified, using the Nested Knowledge AutoLit platform, prospective studies that reported 90-day outcomes in males and females treated with EVT for AIS. The primary outcome of interest was 90-day modified Rankin Scale (mRS) 0-2. Secondary outcome variables included mRS 0-1, symptomatic intracranial hemorrhage (sICH), thrombolysis in cerebral infarction (TICI) score 2b-3, and mortality. Using R software version 4.1.2, we calculated pooled odds ratios (ORs) and their corresponding 95% confidence intervals (CI). RESULTS: We included 10 studies with 10,209 patients. There was no difference between males and females in rate of mRS 0-2 (OR= 1.16; 95% CI= 0.87-1.56; P-value= 0.316); however, after removing outliers, males had higher rates of mRS 0-2 (OR= 1.40; 95% CI= 1.19-1.66; P-value< 0.001). Similar results were reported for mRS 0-1 (OR= 1.21; 95% CI= 0.93-1.56; P-value= 0.15), after removing outliers (OR= 1.32; 95% CI= 1.17-1.50; P-value< 0.001). There was no difference between males and females in rate of sICH (OR= 0.89; 95% CI= 0.74-1.08; P-value= 0.246), mortality (OR= 0.88; 95% CI= 0.74-1.05; P-value= 0.15), or TICI 2b-3 (OR= 1.19; 95% CI= 0.85-1.67; P-value= 0.309). CONCLUSIONS: Males tend to experience better outcomes following EVT for AIS, even in the setting of similar reperfusion. The mechanisms underlying this phenomenon remain unclear, and further research is warranted. EVT remains a safe and effective option for both males and females with AIS.