Predictors of Intrahospital Mortality in Aneurysmal Subarachnoid Hemorrhage after Endovascular Embolization.

Background and Objectives: Aneurysmal subarachnoid hemorrhage (ASAH) is defined as bleeding in the subarachnoid space caused by the rupture of a cerebral aneurysm. About 11% of people who develop ASAH die before receiving medical treatment, and 40% of patients die within four weeks of being admitted to hospital. There are limited data on single-center experiences analyzing intrahospital mortality in ASAH patients treated with an endovascular approach. Given that, we wanted to share our experience and explore the risk factors that influence intrahospital mortality in patients with ruptured intracranial aneurysms treated with endovascular coil embolization. Materials and Methods: Our study was designed as a clinical, observational, retrospective cross-sectional study. It was performed at the Department for Radiology, University Clinical Center Kragujevac in Kragujevac, Serbia. The study inclusion criteria were ≥18 years, admitted within 24 h of symptoms onset, acute SAH diagnosed on CT, aneurysm on DSA, and treated by endovascular coil embolization from January 2014 to December 2018 at our institution. Results: A total of 66 patients were included in the study-48 (72.7%) women and 18 (27.3%) men, and 19.7% of the patients died during hospitalization. After adjustment, the following factors were associated with in-hospital mortality: a delayed ischemic neurological deficit, the presence of blood in the fourth cerebral ventricle, and an elevated urea value after endovascular intervention, increasing the chances of mortality by 16.3, 12, and 12.6 times. Conclusions: Delayed cerebral ischemia and intraventricular hemorrhage on initial head CT scan are strong predictors of intrahospital mortality in ASAH patients. Also, it is important to monitor kidney function and urea levels in ASAH patients, considering that elevated urea values after endovascular aneurysm embolization have been shown to be a significant risk factor for intrahospital mortality.

Prompt closure versus gradual weaning of external ventricular drain for hydrocephalus following aneurysmal subarachnoid haemorrhage: a statistical analysis plan for the DRAIN randomised clinical trial.

BACKGROUND: Insertion of an external ventricular drain (EVD) is a first-line treatment of acute hydrocephalus caused by aneurysmal subarachnoid haemorrhage (aSAH). Once the patient is clinically stable, the EVD is either removed or replaced by a permanent internal shunt. The optimal strategy for cessation of the EVD is unknown. Prompt closure carries a risk of acute hydrocephalus or redundant shunt implantations, whereas gradual weaning may increase the risk of EVD-related infections. METHODS: DRAIN (Danish RAndomised Trial of External Ventricular Drainage Cessation IN Aneurysmal Subarachnoid Haemorrhage) is an international multicentre randomised clinical trial comparing prompt closure versus gradual weaning of the EVD after aSAH. The primary outcome is a composite of VP-shunt implantation, all-cause mortality, or EVD-related infection. Secondary outcomes are serious adverse events excluding mortality and health-related quality of life (EQ-5D-5L). Exploratory outcomes are modified Rankin Scale, Fatigue Severity Scale, Glasgow Outcome Scale Extended, and length of stay in the neurointensive care unit and hospital. Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, alpha 5%, power 80%), 122 participants are required in each intervention group. Outcome assessment for the primary outcome, statistical analyses, and conclusion drawing will be blinded. Two independent statistical analyses and reports will be tracked using a version control system, and both will be published. Based on the final statistical report, the blinded steering group will formulate two abstracts. CONCLUSION: We present a pre-defined statistical analysis plan for the randomised DRAIN trial, which limits bias, p-hacking, and data-driven interpretations. This statistical analysis plan is accompanied by tables with simulated data, which increases transparency and reproducibility. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256. Registered on May 13, 2019.

Dental pulp mesenchymal stem cell-derived exosomes inhibit neuroinflammation and microglial pyroptosis in subarachnoid hemorrhage via the miRNA-197-3p/FOXO3 axis.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a severe stroke subtype that lacks effective treatment. Exosomes derived from human dental pulp stem cells (DPSCs) are a promising acellular therapeutic strategy for neurological diseases. However, the therapeutic effects of DPSC-derived exosomes (DPSC-Exos) on SAH remain unknown. In this study, we investigated the therapeutic effects and mechanisms of action of DPSC-Exos in SAH. MATERIALS AND METHODS: SAH was established using 120 male Sprague-Dawley rats. One hour after SAH induction, DPSC-Exos were administered via tail vein injection. To investigate the effect of DPSC-Exos, SAH grading, short-term and long-term neurobehavioral assessments, brain water content, western blot (WB), immunofluorescence staining, Nissl staining, and HE staining were performed. The role of miR-197-3p/FOXO3 in regulating pyroptosis was demonstrated through miRNA sequencing, bioinformatics analysis, and rescue experiments. The SAH model in vitro was established by stimulating BV2 cells with hemoglobin (Hb) and the underlying mechanism of DPSC-Exos was investigated through WB and Hoechst/PI staining. RESULTS: The expressions of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) were increased after SAH. DPSC-Exos alleviated brain edema and neuroinflammation by inhibiting the expression of FOXO3 and reducing NLRP3 inflammasome activation, leading to improved neurobehavioral functions at 24 h after SAH. In vitro, the expression of the NLRP3 inflammasome components (NLRP3 and caspase1-p20), GSDMD-N, and IL-18 was inhibited in BV2 cells pretreated with DPSC-Exos. Importantly, DPSC-Exos overexpressing miR-197-3p had a more obvious protective effect than those from NC-transfected DPSCs, while those from DPSCs transfected with the miR-197-3p inhibitor had a weaker protective effect. Functional studies indicated that miR-197-3p bound to the 3'-untranslated region of FOXO3, inhibiting its transcription. Furthermore, the overexpression of FOXO3 reversed the protective effects of miR-197-3p. CONCLUSIONS: DPSC-Exos inhibited activation of the NLRP3 inflammasome and related cytokine release via the miR-197-3p/FOXO3 pathway, alleviated neuroinflammation, and inhibited microglial pyroptosis. These findings suggest that using DPSC-Exos is a promising therapeutic strategy for SAH.

Identification of metabolites associated with preserved muscle volume after aneurysmal subarachnoid hemorrhage due to high protein supplementation and neuromuscular electrical stimulation.

The INSPIRE randomized clinical trial demonstrated that a high protein diet (HPRO) combined with neuromuscular electrical stimulation (NMES) attenuates muscle atrophy and may improve outcomes after aneurysmal subarachnoid hemorrhage We sought to identify specific metabolites mediating these effects. Blood samples were collected from subjects on admission prior to randomization to either standard of care (SOC; N = 12) or HPRO + NMES (N = 12) and at 7 days. Untargeted metabolomics were performed for each plasma sample. Sparse partial least squared discriminant analysis identified metabolites differentiating each group. Correlation coefficients were calculated between each metabolite and total protein per day and muscle volume. Multivariable models determined associations between metabolites and muscle volume. Unique metabolites (18) were identified differentiating SOC from HPRO + NMES. Of these, 9 had significant positive correlations with protein intake. In multivariable models, N-acetylleucine was significantly associated with preserved temporalis [OR 1.08 (95% CI 1.01, 1.16)] and quadricep [OR 1.08 (95% CI 1.02, 1.15)] muscle volume. Quinolinate was also significantly associated with preserved temporalis [OR 1.05 (95% CI 1.01, 1.09)] and quadricep [OR 1.04 (95% CI 1.00, 1.07)] muscle volume. N-acetylserine and ß-hydroxyisovaleroylcarnitine were associated with preserved temporalis or quadricep volume. Metabolites defining HPRO + NMES had strong correlations with protein intake and were associated with preserved muscle volume.

Emergent Management of Spontaneous Subarachnoid Hemorrhage.

OBJECTIVE: Spontaneous subarachnoid hemorrhage (SAH) carries high morbidity and mortality rates, and the emergent management of this disease can make a large impact on patient outcome. The purpose of this article is to provide a pragmatic overview of the emergent management of SAH. LATEST DEVELOPMENTS: Recent trials have influenced practice around the use of antifibrinolytics, the timing of aneurysm securement, the recognition of cerebral edema and focus on avoiding a lower limit of perfusion, and the detection and prevention of delayed cerebral ischemia. Much of the acute management of SAH can be protocolized, as demonstrated by two updated guidelines published by the American Heart Association/American Stroke Association and the Neurocritical Care Society in 2023. However, the gaps in evidence lead to clinical equipoise in some aspects of critical care management. ESSENTIAL POINTS: In acute management, there is an urgency to differentiate the etiology of SAH and take key emergent actions including blood pressure management and coagulopathy reversal. The critical care management of SAH is similar to that of other acute brain injuries, with the addition of detecting and treating delayed cerebral ischemia. Strategies for the detection and treatment of delayed cerebral ischemia are limited by disordered consciousness and may be augmented by monitoring and imaging technology.

[Chinese guideline for the clinical management of patients with ruptured intracranial aneurysms (2024)].

Subarachnoid hemorrhage caused by intracranial aneurysm (aneurysmal subarachnoid hemorrhage,aSAH) poses a significant threat to the health of the Chinese people. The prognosis of aSAH patients is poor, with a mortality of up to 50%, which is a public health problem in China. The clinical evaluation, surgical ctrategies, and perioperative management are important parts of clinical management for aSAH patients. This clinical management guideline consists of 112 recommendations on epidemiology, clinical imaging diagnosis, prognosis evaluation, treatment strategies and selection, anesthesia management, perioperative care, and management of special populations with aSAH, aiming to provide clinical guidance for clinical doctors and related professionals.

[Interpretation of Chinese guideline for the clinical management of patients with ruptured intracranial aneurysms (2024)].

Aneurysmal subarachnoid hemorrhage (aSAH) is a life-threatening neurological emergency with high mortality, and even patients receiving optimal medical care may develop long-term disability, which seriously affects their quality of life and increases the heavy medical burden on society and families. To provide comprehensive clinical management advice, the Society of Neurosurgery of the Chinese Medical Association, the Society of the Chinese Stroke Association of the National Medical Center for Neurological Diseases, and the National Clinical Research Center for Neurological Diseases jointly formulate "Chinese Guidelines for the Clinical Management of Patients With Ruptured Intracranial Aneurysms in 2024". The evidence sources are divided into the Chinese population and other populations, using a modular format to provide recommendations, summaries of relevant opinions, and future research directions on epidemiology, clinical imaging diagnosis, prognosis evaluation, treatment strategies and choices, anesthesia management, perioperative care, and recommendations for the management of aSAH in special populations. It provides practical clinical guidance and recommendations for doctors and related professionals.

Sex differences in the use of mechanical ventilation in a neurointensive care population: a retrospective study.

BACKGROUND: In the general intensive care unit (ICU) women receive invasive mechanical ventilation (IMV) less frequently than men. We investigated whether sex differences in the use of IMV also exist in the neurocritical care unit (NCCU), where patients are intubated not only due to respiratory failure but also due to neurological impairment. METHODS: This retrospective single-centre study included adults admitted to the NCCU of the University Hospital Zurich between January 2018 and August 2021 with neurological or neurosurgical main diagnosis. We collected data on demographics, intubation, re-intubation, tracheotomy, and duration of IMV or other forms of respiratory support from the Swiss ICU registry or the medical records. A descriptive statistics was performed. Baseline and outcome characteristics were compared by sex in the whole population and in subgroup analysis. RESULTS: Overall, 963 patients were included. No differences between sexes in the use and duration of IMV, frequency of emergency or planned intubations, tracheostomy were found. The duration of oxygen support was longer in women (men 2 [2, 4] vs. women 3 [1, 6] days, p = 0.018), who were more often admitted due to subarachnoid hemorrhage (SAH). No difference could be found after correction for age, diagnosis of admission and severity of disease. CONCLUSION: In this NCCU population and differently from the general ICU population, we found no difference by sex in the frequency and duration of IMV, intubation, reintubation, tracheotomy and non-invasive ventilation support. These results suggest that the differences in provision of care by sex reported in the general ICU population may be diagnosis-dependent. The difference in duration of oxygen supplementation observed in our population can be explained by the higher prevalence of SAH in women, where we aim for higher oxygenation targets due to the specific risk of vasospasm.

Predictors of Outcome in Aneurysmal Subarachnoid Hemorrhage: A Tertiary Center Experience.

AIM: To determine the risk factors affecting the mortality rate and outcomes of patients with subarachnoid hemorrhage (SAH). MATERIAL AND METHODS: The records of patients who underwent aneurysm treatment and intensive care unit (ICU) followup in our hospital between 2013-2021 were reviewed retrospectively. Demographics of the patients, aneurysm characteristics, complications in the ICU, the Hunt Hess score, Glasgow Coma Scale (GCS), Acute Physiologic Assessment and Chronic Health Evaluation II score (APACHE II), sepsis status, and mechanical ventilation (MV) needed during ICU admission were collected. The generalized linear mixed modeling method was used to determine independent risk factors affecting mortality. RESULTS: The records of 91 patients who met the inclusion criteria were analyzed. The age of the patients ranged from 21 to 86 years, and the female-to-male ratio was 6 / 7, with a mean age of 49.9 ± 13.06 years. The aneurysm treatment modality was surgical in 79 patients (86.8%) and endovascular in 12 patients (13.2%). The length of the ICU stay was mean 10.96 ± 13.66 days. While 64.8% (n=59) of the patients were discharged, 7.7% (n=7) were referred to palliative care units, and 25% (n=25) died. A one-unit increase in the APACHE II score was determined to increase the risk of vasospasm 1.154 times (p < 0.001). Analysis showed that a one-day increase in the MV day increased the mortality risk 1.838 times (p < 0.001), and vasospasm increased the mortality risk 32.151 times (p=0.004) CONCLUSION: The length of hospital stay, the day of MV, and the presence of vasospasm were determined as independent risk factors affecting mortality. Early diagnosis and rapid treatment of vasospasm, which increases mortality during ICU follow-up, positively impact patient outcomes.

Clinical Characteristics and Outcomes of Aneurysmal Subarachnoid Hemorrhage Patients Who Live Alone.

It has been shown that living alone is one of the risk factors for unfavorable outcomes in ischemic stroke patients, mostly due to delay in receiving appropriate treatment. A single-center retrospective observational study was conducted to evaluate whether living alone was associated with unfavorable outcomes in aneurysmal subarachnoid hemorrhage (SAH) patients. Among 451 SAH patients admitted to our institution between January 2013 and December 2022, 43 patients who lived alone had sustained SAH at home (group A) and 329 patients who lived with family had sustained SAH at home (group F). The mortality rate (46.5% vs. 29.8%, p = 0.04) and a tendency for having unfavorable outcomes were higher in group A than in group F. The incidence of concomitant hydrocephalus was significantly higher in the former (37.2% vs. 21.3%, p = 0.03). Group A was further classified to the Able to Call (n = 15, group AC) and Unable to Call (n = 28, group UC) subgroups based on their ability to call for help by themselves. Group AC tended to have favorable outcomes (27% vs. 4%, p = 0.04). Treatment to obliterate a ruptured aneurysm had particularly been challenging in group UC, in which the accurate time of onset often remained unidentifiable: Their overall mortality was as high as 57% and their capability to undergo surgical/interventional treatment was only 67%. Perioperative complications resulting from delayed presentation had been common. Considering the present finding that most of those who lived alone could not call for help, further effort is warranted to facilitate early detection of those patients.

Advances and Future Trends in the Diagnosis and Management of Subarachnoid Hemorrhage.

Major advances in neurocritical care and the modalities used to treat aneurysms have led to improvement in the outlook of patients with aneurysmal subarachnoid hemorrhage. Yet, several knowledge gaps remain widely open. Variability in practices stems from the lack of solid evidence to guide management, which recent guidelines from professional organizations aim to mitigate. In this article, the authors review some of these gaps in knowledge, highlight important messages from recent management guidelines, emphasize aspects of our practice that we consider particularly useful to optimize patient outcomes, and suggest future areas of research.

Association of geographical disparities and segregation in regional treatment facilities for Black patients with aneurysmal subarachnoid hemorrhage in the United States.

Background and objectives: This study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations. Methods: This cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed. Results: 142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division (D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic (D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p < 0.001) were associated a lower likelihood of mortality (OR 0.91, 95% CI 0.82-1.00, p = 0.044 vs. OR 0.75, 95% CI 0.68-0.83, p < 0. 001) (p = 0.049), greater likelihood of tracheostomy tube placement (OR 1.45, 95% CI 1.22-1.73, p < 0.001 vs. OR 1.87, 95% CI 1.59-2.21, p < 0.001) (p < 0. 001), and lower likelihood of receiving palliative care (OR 0.88, 95% CI 0.76-0.93, p < 0.001 vs. OR 0.67, 95% CI 0.59-0.77, p < 0.001) (p = 0.029). Conclusion: This study demonstrates regional differences in disparities for Black patients with aSAH, particularly in end-of-life care, with varying levels of segregation in regional treatment facilities playing an associated role. The findings underscore the need for targeted interventions and policy changes to address systemic healthcare inequities, reduce segregation, and ensure equitable access to high-quality care for all patients.

Global Disparities in the Presentation and Management of Aneurysmal Subarachnoid Hemorrhage: A Review and Analysis.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality rates. There is a significant gap in the literature describing global disparities in demographics, management, and outcomes among patients with aSAH. We aimed to conduct a systematic review and meta-analysis to assess global disparities in aSAH presentation and management. METHODS: PubMed and Embase databases were queried from earliest records to November 2022 for aSAH literature. Presentation, demographics, comorbidities, treatment methods, and outcomes data were collected. Articles that did not report aSAH-specific patient management and outcomes were excluded. Pooled weighted prevalence rates were calculated. Random effects model rates were reported. RESULTS: After screening, 33 articles representing 10,553 patients were included. The prevalence of Fisher grade 3 or 4 aSAH in high- and lower-income countries (HIC and LIC), respectively, was 79.8% (P < 0.01) and 84.1 (P < 0.01). Prevalence of male aSAH patients in HIC and LIC, respectively, was 35.8% (P < 0.01) and 45.0% (P < 0.01). Prevalence of treatment in aSAH patients was 99.5% (P < 0.01) and 99.4% (P = 0.16) in HIC and LIC, respectively. In HIC, 35% (P < 0.01) of aneurysms in aSAH patients were treated with coiling. No LIC reported coiling for aSAH treatment; LIC only reported rates of surgical clipping, with a total prevalence of 92.4% (P < 0.01) versus 65.6% (P < 0.01) in HIC. CONCLUSION: In this analysis, we found similar rates of high-grade SAH hemorrhages in HIC and LIC but a lack of endovascular coil embolization treatments reported in LIC. Additional research and discussion are needed to identify reasons for treatment disparities and intervenable societal factors to improve aSAH outcomes worldwide.

Contemporary management of aneurysmal subarachnoid haemorrhage. An update for the intensivist.

Aneurysmal subarachnoid haemorrhage (aSAH) is a rare yet profoundly debilitating condition associated with high global case fatality and morbidity rates. The key determinants of functional outcome include early brain injury, rebleeding of the ruptured aneurysm and delayed cerebral ischaemia. The only effective way to reduce the risk of rebleeding is to secure the ruptured aneurysm quickly. Prompt diagnosis, transfer to specialized centers, and meticulous management in the intensive care unit (ICU) significantly improved the prognosis of aSAH. Recently, multimodality monitoring with specific interventions to correct pathophysiological imbalances has been proposed. Vigilance extends beyond intracranial concerns to encompass systemic respiratory and haemodynamic monitoring, as derangements in these systems can precipitate secondary brain damage. Challenges persist in treating aSAH patients, exacerbated by a paucity of robust clinical evidence, with many interventions showing no benefit when tested in rigorous clinical trials. Given the growing body of literature in this field and the issuance of contemporary guidelines, our objective is to furnish an updated review of essential principles of ICU management for this patient population. Our review will discuss the epidemiology, initial stabilization, treatment strategies, long-term prognostic factors, the identification and management of post-aSAH complications. We aim to offer practical clinical guidance to intensivists, grounded in current evidence and expert clinical experience, while adhering to a concise format.

Trends in incidence and treatments of spontaneous subarachnoid hemorrhage- a 10 year hospital based study.

BACKGROUND: Improved endovascular methods make it possible to treat complex ruptured aneurysms, but surgery is still needed in certain cases. We evaluated the effects on the clinical results of the changes in aneurysm treatment. METHODS: The study cohort was 837 patients with spontaneous subarachnoid hemorrhage (SAH) and one or multiple aneurysms, admitted to Dept of Neurosurgery, Uppsala University Hospital from 2012 to 2021. Demography, location and treatment of aneurysms, neurologic condition at admission and discharge, mortality and last tier treatment of high intracranial pressure (ICP) was evaluated. Functional outcome was measured using the Extended Glasgow Outcome Scale (GOSE) Data concerning national incidences of stroke diseases was collected from open Swedish databases. RESULTS: Endovascular methods were used in 666 cases (79.6%). In 111 (13.3%) with stents. Surgery was performed in 115 cases (13.7%) and 56 patients (6.7%) had no aneurysm treatment. The indications for surgery were a hematoma (51 cases, 44.3%), endovascular treatment not considered safe (47 cases, 40.9%), or had been attempted without success (13 cases, 11.3%). Treatment with stent devices increased, and with surgery decreased over time. There was a trend in decrease in hemicraniectomias over time. Both the patient group admitted awake (n = 681) and unconscious (n = 156) improved significantly in consciousness between admission and discharge. Favorable outcome (GOSE 5-8) was seen in 69% for patients admitted in Hunt & Hess I-II and 25% for Hunt & Hess III-V. Mortality at one year was 10.9% and 42.7% for those admitted awake and unconscious, respectively.The number of cases decreased during the study period, which was in line with Swedish national data. CONCLUSIONS: The incidence of patients with SAH gradually decreased in our material, in line with national data. The treatment policy in our unit has been shifting to more use of endovascular methods. During the study period the use of hemicraniectomies decreased.