Severe Subarachnoid Hemorrhage Research Articles

Establishment of a novel protocol for assessing the severity of subarachnoid hemorrhage in circle Willis perforation mouse model

The Circle of Willis perforation (cWp) mouse model is a key tool in subarachnoid hemorrhage (SAH) research; however, inconsistent bleeding volumes can challenge experimental reliability. To address this issue, we introduced the ROB Scoring System, a novel protocol integrating Rotarod Tests (RT), Open-field Tests (OT) video analysis, and daily Body Weight Loss (BWL) monitoring to precisely categorize SAH severity. Forty C57BL/6 mice underwent cWp SAH induction, categorized by ROB into severity subgroups (severe, moderate, mild). Validation compared ROB trends in subgroups, and ROB outcomes with autopsy results on postoperative days three and seven for acute and sub-acute evaluations. Mortality rates were analyzed via the survival log-rank test, revealing a significant difference among SAH subgroups (P < 0.05). Strong correlations between ROB grades and autopsy findings underscored its precision. Notably, the severe group exhibited 100% mortality within 4 days post SAH onset. Single parameters (RT, OT, BWL) were insufficient for distinguishing SAH severity levels. The ROB score represents a significant advancement, offering an objective method for precise categorization and addressing inherent bleeding variations in the cWp SAH model. This standardized protocol enhances the reliability and effectiveness of the SAH translational research, providing a valuable tool for future investigations into this critical area.

Outcomes of heparin-induced thrombocytopenia type II in aneurysmal subarachnoid hemorrhage patients: A US nationwide analysis.

Despite the widespread use of heparin during and following endovascular procedures in the management of aneurysmal subarachnoid hemorrhage (SAH) patients, limited research has explored the incidence and impact of heparin-induced thrombocytopenia (HIT) on SAH. Descriptive statistics, multivariate regressions, and propensity score-matching were employed to compare clinical characteristics, comorbidities, interventions, complications, and outcomes of HIT in SAH patients identified within the US National Inpatient Sample database from 2010 to 2019. Among 76 387 SAH patients from 2010 to 2019, 166 (0.22%) developed HIT. HIT was identified as a significant predictor of prolonged length of stay (OR 6.799, 95% CI 3.985 to 11.6, P<0.01) and poor functional outcomes (OR 2.541, 95% CI 1.628 to 3.966, P<0.01) after adjusting for relevant factors. HIT incidence was higher in patients with elevated SAH severity scores (1.42 vs 1.06, P<0.01), younger patients (58.04 vs 61.39 years, P=0.01), overweight individuals (0.4% vs 0.2%, P<0.01), those on long-term anticoagulants (10.84% vs 5.72%, P<0.01), or with a cerebrospinal fluid drainage device (external ventricular drain, ventriculoperitoneal shunt; P<0.01). HIT patients showed increased rates of endovascular coiling, ventricular drain placement, shunt placement, deep vein thrombosis, urinary tract infection, acute kidney injury, pulmonary embolism, venous sinus thrombosis, pneumonia, and cerebral vasospasm (all P<0.01). SAH patients with HIT exhibited various comorbidities and increased rates of complications, which may contribute to extended hospital stays. This nationwide study aids clinical suspicion and highlights HIT's impact on SAH patients.

Exploring the Role of Ferroptosis-Related Circular RNAs in Subarachnoid Hemorrhage.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event associated with high mortality and significant morbidity. Recent studies have highlighted the emerging role of ferroptosis, a novel form of regulated cell death, in the pathogenesis of SAH. Circular RNAs (circRNAs), have been found to play essential roles in various cellular processes, including gene regulation and disease pathogenesis. The expression profile of circRNAs in neural tissues, particularly in the brain, suggests their critical role in synaptic function and neurogenesis. Moreover, the interplay between circRNAs and ferroptosis-related pathways, such as iron metabolism and lipid peroxidation, is explored in the context of SAH. Understanding the functional roles of specific circRNAs in the context of SAH may provide potential therapeutic targets to attenuate ferroptosis-associated brain injury. Furthermore, the potential of circRNAs as diagnostic biomarkers for SAH severity, prognosis, and treatment response is discussed. Overall, this review highlights the significance of studying the intricate interplay between circRNAs and ferroptosis in the context of SAH. Unraveling the mechanisms by which circRNAs modulate ferroptotic cell death may pave the way for the development of novel therapeutic strategies and diagnostic approaches for SAH management, ultimately improving patient outcomes and quality of life.

Rates of operative intervention and in-hospital mortality following subarachnoid hemorrhage in patients with COVID-19.

COVID-19 had massive effects on the healthcare system and multifactorial implications for the management of intensive care unit and cerebrovascular patients. This study aimed to assess the effect of COVID-19 on the outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH). The National Inpatient Sample (NIS) was used to identify patients with nontraumatic SAH (ICD-10 code I60.x). Patients with nonaneurysmal cerebrovascular malformations or traumatic intracranial injuries were excluded. Only patients managed from April to December 2020 were included in the study given the availability of an ICD-10 code for COVID-19. Data on sociodemographic factors, hospital characteristics, comorbidities, NIS SAH Severity Score (NIS-SSS), surgical treatment, and death were acquired. Multivariable analysis was used to assess predictors of both surgical intervention and in-hospital mortality. In total, 6984 patients met the study criteria, 359 (5.1%) of whom had COVID-19. Those with COVID-19 were more likely to be younger and male and had a higher All Patient Refined Diagnosis-Related Groups illness severity subclass, and NIS-SSS. Moreover, patients with COVID-19 were less likely to undergo surgery (10.0% vs 23.6%, OR 0.35, p < 0.0001) and had significantly higher mortality rates (48.2% vs 22.7%, p < 0.0001). When controlling for other variables, COVID-19 was an independent predictor of death (OR 1.67, p = 0.0002). Aneurysm surgery was performed in 1597 patients (317 open and 1280 endovascular procedures). There was no difference between the cohorts positive and negative for COVID-19 in terms of time to surgery or type of surgery. COVID-19 had significant impacts on patients with nontraumatic SAH. Specifically, patients with COVID-19 were significantly less likely to undergo surgery and had higher in-hospital mortality rates; however, for patients who did undergo procedural intervention, there was no significant difference in the type of intervention. Multiple factors, from medical acuity to healthcare system limitations, may contribute to these findings. Further retrospective research is needed to identify both specific causes of lower intervention rates and other potential nonaneurysmal causes of SAH in patients with COVID-19.

Systemic tolerance of intravenous milrinone administration for cerebral vasospasm secondary to non-traumatic subarachnoid hemorrhage

PurposeDelayed cerebral ischemia (DCI) is a severe subarachnoid hemorrhage (SAH) complication, closely related to cerebral vasospasm (CVS). CVS treatment frequently comprises intravenous milrinone, an inotropic and vasodilatory drug. Our objective is to describe milrinone's hemodynamic, respiratory and renal effects when administrated as treatment for CVS. MethodsRetrospective single-center observational study of patients receiving intravenous milrinone for CVS with systemic hemodynamics, oxygenation, renal disorders monitoring. We described these parameters' evolution before and after milrinone initiation (day – 1, baseline, day 1 and day 2), studied treatment cessation causes and assessed neurological outcome at 3–6 months. ResultsNinety-one patients were included. Milrinone initiation led to cardiac output increase (4.5 L/min [3.4–5.2] at baseline vs 6.6 L/min [5.2–7.7] at day 2, p < 0.001), Mean Arterial Pressure decrease (101 mmHg [94–110] at baseline vs 95 mmHg [85–102] at day 2, p = 0.001) norepinephrine treatment requirement increase (32% of patients before milrinone start vs 58% at day 1, p = 0.002) and slight PaO2/FiO2 ratio deterioration (401 [333–406] at baseline vs 348 [307–357] at day 2, p = 0.016). Milrinone was interrupted in 8% of patients. 55% had a favorable outcome. ConclusionIntravenous milrinone for CVS treatment seems associated with significant impact on systemic hemodynamics leading sometimes to treatment discontinuation.

Subarachnoid Hemorrhage Trials: Cutting, Sliding, or Keeping mRS Scores and WFNS Grades.

Rigorous evidence generation with randomized controlled trials has lagged for aneurysmal subarachnoid hemorrhage (SAH) compared with other forms of acute stroke. Besides its lower incidence compared with other stroke subtypes, the presentation and outcome of patients with SAH also differ. This must be considered and adjusted for in designing pivotal randomized controlled trials of patients with SAH. Here, we show the effect of the unique expected distribution of the SAH severity at presentation (World Federation of Neurological Surgeons grade) on the outcome most used in pivotal stroke randomized controlled trials (modified Rankin Scale) and, consequently, on the sample size. Furthermore, we discuss the advantages and disadvantages of different options to analyze the outcome and control the expected distribution of the World Federation of Neurological Surgeons grades in addition to showing their effects on the sample size. Finally, we offer methods that investigators can adapt to more precisely understand the effect of common modified Rankin Scale analysis methods and trial eligibility pertaining to the World Federation of Neurological Surgeons grade in designing their large-scale SAH randomized controlled trials.

Circadian dependency of microglial heme oxygenase-1 expression and inflammation determine neuronal injury in hemorrhagic stroke

BackgroundThe heme oxygenase-1 (HO-1) enzyme pathway is of crucial importance in the removal of toxic blood components and regulation of neuroinflammation following hemorrhagic stroke. Although a circadian pattern dependency in the incidence and severity of hemorrhagic stroke exists, it is unknown whether the activity of the HO-1 system in the context of hemorrhagic injury also exhibits circadian dependency. We hypothesized that the circadian regulation of microglial HO-1 would determine the extent of neuroinflammation and neuronal injury in a murine model of subarachnoid hemorrhage (SAH).MethodsIn vitro expression patterns of HO-1 and circadian rhythm genes were analyzed in the microglial BV-2 cell line and primary microglia (PMG) using Western blot and qPCR. PMG isolated from Hmox1fl/fl and LyzM-Cre-Hmox1fl/fl mice were used to evaluate the role of microglial HO-1. We further investigated the in vivo relevance in a murine subarachnoid hemorrhage (SAH) model using Hmox1fl/fl and LyzM-Cre-Hmox1fl/fl mice with myeloid cell HO-1 deficiency, inducing SAH at different zeitgeber (ZT) times and analyzing the expression of HO-1 and the circadian control gene Period-2 (Per-2), respectively. Furthermore, we measured the inflammatory cytokine Monocyte Chemoattractant Protein-1 (MCP-1) in the cerebrospinal fluid of SAH patients in correlation with clinical outcome.ResultsHO-1 baseline expression and response to CO with blood exposure depended on ZT. In vitro expression of circadian control genes was de-synchronized in LyzM-Cre-Hmox1fl/fl PMG and did not respond to exogenous CO exposure. We found that circadian rhythm plays a crucial role in brain damage after SAH. At ZT2, we observed less phagocytic function, more vasospasm and increased microglial activation. CO reduced mortality at ZT12 in HO-1 deficient mice and reduced the difference between ZT2 and ZT12 in the inflammatory response. Induction of MCP-1 in the CSF from SAH patients was time-dependent and correlated with the expression of circadian control genes, SAH severity, functional impairment and delirium.ConclusionsOur data point towards a crucial role for the HO-1 enzyme system and circadian control in neuronal injury after a hemorrhagic stroke.

Intrahospital Transport of Critically Ill Patients with Subarachnoid Hemorrhage-Frequency, Timing, Complications, and Clinical Consequences.

Patients with subarachnoid hemorrhage (SAH) often necessitate intra-hospital transport (IHT) during intensive care treatment. These transfers to facilities outside of the neurointensive care unit (NICU) pose challenges due to the inherent instability of the hemodynamic, respiratory, and neurological parameters that are typical in these patients. In this retrospective, single-center cohort study, a total of 108 IHTs were analyzed for demographics, transport rationale, clinical outcomes, and pre/post-IHT monitoring parameters. After establishing clinical thresholds, the frequency of complications was calculated, and predictors of thresholds violations were determined. The mean age was 55.7 (+/-15.3) years, with 68.0% showing severe SAH (World Federation of Neurosurgical Societies Scale 5). IHTs with an emergency indication made up 30.8% of all transports. Direct therapeutic consequences from IHT were observed in 38.5%. On average, the first IHT occurred 1.5 (+/-2.0) days post-admission and patients were transported 4.3 (+/-1.8) times during their stay in the NICU. Significant parameter changes from pre- to post-IHT included mean arterial pressure, systolic blood pressure, oxygen saturation, blood glucose levels, temperature, dosages of propofol and ketamine, tidal volume, inspired oxygen concentration, Horovitz index, glucose, pH, intracranial pressure, and cerebral perfusion pressure. Relevant hemodynamic thresholds were violated in 31.5% of cases, while respiratory complications occurred in 63.9%, and neurological complications in 20.4%. For hemodynamic complications, a low heart rate with a threshold of 61/min (OR 0.96, 95% CI 0.93-0.99, p = 0.0165) and low doses of midazolam with a threshold of 17.5 mg/h (OR 0.97, 95% CI 0.95-1.00, p = 0.0232) significantly predicted adverse events. However, the model did not identify significant predictors for respiratory and neurological outcomes. Conclusively, IHTs in SAH patients are associated with relevant changes in hemodynamic, respiratory, and neurological monitoring parameters, with direct therapeutic consequences in 4/10 IHTs. These findings underscore the importance of further studies on the clinical impact of IHTs.

Association between transcutaneous oxygen saturation within 24 h of admission and mortality in critically ill patients with non-traumatic subarachnoid hemorrhage: a retrospective analysis of the MIMIC-IV database.

In critically ill patients, transcutaneous oxygen saturation (SpO2) upon admission is typically associated with in-hospital mortality. Nevertheless, the available information for patients with non-traumatic subarachnoid hemorrhage (SAH) is limited. In our study, our objective was to assess the correlation between SpO2 levels and mortality among patients diagnosed with severe SAH. In this study, we extracted data from the Medical Information Marketplace in Intensive Care (MIMIC-IV) database, which comprises information on critically ill patients. By employing matching ICD-9 and ICD-10 codes, we identified 3,328 patients diagnosed with SAH. Every individual who was admitted to the intensive care unit (ICU) had their SpO2 data and various covariates, including age, sex, diagnosis, and duration of stay, recorded upon admission. Subsequently, the patients were categorized into three distinct groups according to their SpO2 levels: low (≤95%), moderate (95-98%), and high (≥98%). To investigate the association between percutaneous oxygen saturation and mortality in patients with severe SAH, logistic regression, and cubic spline models were utilized. The main outcomes of interest were 28- and 90-day mortality rates. Additionally, subgroup analyses were conducted to evaluate these correlations and assess the consistency of interactions. A cohort of 864 patients diagnosed with non-traumatic SAH was included in this study. The correlation between SpO2 and mortality displayed a U-shaped curve when utilizing a finite cubic spline function (non-linearity < 0.001), with the nadir in the probability of in-hospital death at 96%. Mortality at 28 and 90 days showed an inverse correlation with SpO2 < 96% (adjusted odds ratio [OR], 0.8; 95% confidence interval [CI], 0.67-0.95, and 0.76; 95% CI, 0.6-0.96). Conversely, there was a positive correlation between percutaneous oxygen saturation (SpO2) levels of ≥96% and mortality rates at both 28 and 90 days (adjusted OR, 1.17; 95% CI, 1.02-1.35 and 1.2; 95% CI, 1.05-1.39). In patients with severe subarachnoid hemorrhage, the association between SpO2 and mortality at 28 and 90 days demonstrated a U-shaped pattern. When SpO2 levels were between 95 and 98%, both short- and long-term mortality rates were at their lowest. Patients with significant subarachnoid hemorrhage had a lower chance of survival when their SpO2 values were either high or low.

The effect of green channel for stroke patients on treatment of severe aneurysmal subarachnoid hemorrhage

PurposeTo explore the effect of green channel for stroke patients on the treatment of severe aneurysmal subarachnoid hemorrhage. MethodsThis is a retrospective case-control study. The clinical data of patients with severe aneurysmal subarachnoid hemorrhage admitted to the emergency department of our hospital from January 2015 to June 2022 were retrospectively analyzed. Patients diagnosed with subarachnoid hemorrhage, confirmed intracranial aneurysm by preoperative CT angiography or digital subtraction, graded Hunt-Hess grade III, IV, and V, < 72 h from the onset to the time of consultation received surgical treatment in our hospital were included in this study. Patients with serious underlying diseases, such as heart, liver, kidney diseases, or malignant tumors, traumatic subarachnoid hemorrhage, previous history of cerebral hemorrhage, and incomplete data were excluded. The control group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2015 to December 2018 before the establishment of the green channel for stroke patients, and the observation group included patients with severe aneurysmal subarachnoid hemorrhage admitted from January 2019 to June 2022 after the establishment of the green channel. The control group received routine treatment in the emergency department; the observation group received improved treatment of green channel for stroke patients. Gender, age, Hunt-Hess grade on admission, modified Rankin scale (mRS) on admission, aneurysm location, aneurysm size and whether accompanied by intracerebral hemorrhage, the time from onset to emergency department, the time from emergency department to vascular diagnostic examination, the time from onset to surgery, the time from emergency department to surgery, the time from hospital admission to surgery, length of hospital stay, complications, treatment effect were analyzed and compared between the 2 groups. SPSS 23.0 software was utilized to conduct comparisons between the 2 groups. The t-test, Chi-square test, or Mann-Whitney U test was chosen based on the data type. Statistical significance was established when p < 0.05. ResultsA total of 71 patients were included in this study, of whom 37 were in the control group and 34 were in the observation group. There were no statistical differences in age, gender, Hunt-Hess grade, mRS scores, aneurysm location, aneurysm size, intracerebral hemorrhage, the time from onset to emergency department, length of hospital stay, complications between the observation group and the control group (all p > 0.05). The time (min) from visit to vascular diagnostic test (60.50 vs. 120.00, p = 0.027), the time (min) from onset to surgery (1792.00 vs. 2868.00, p = 0.023), the time (min) from emergency department to surgery (1568.50 vs. 2778.00, p = 0.016), the time (min) from hospital admission to surgery (1188.50 vs. 2708.00, p = 0.043), all of them were shorter in the observation group than those in the control group. The relative values of admission and 7-day postoperative mRS scores and the relative values of admission and discharge mRS scores ≥ 2 were used as the criteria for determining better efficacy, and the treatment effect was better than that in the control group, and the differences were statistically significant (admission to 7 days postoperative mRS score ≥ 2, 17 (50.0 %) vs. 8 (21.6 %), p = 0.012; admission to discharge mRS score ≥ 2, 19 (55.9 %) vs. 11 (29.7 %), p = 0.026). ConclusionThe green channel for stroke patients with severe aneurysmal subarachnoid hemorrhage can effectively shorten the time from arrival at the emergency department to vascular diagnostic examination and the time from the emergency department to surgery, and achieve a better therapeutic effect, which is worth popularizing and applying.

Abstract 005: Outcomes of Heparin Induced Thrombocytopenia Type II in Aneurysmal Subarachnoid Hemorrhage Patients

Introduction Heparin‐induced thrombocytopenia (HIT) is a rare complication characterized by a decreased platelet count and hypercoagulability following heparin and light‐molecular weight heparin administration. Both anticoagulants can be used intraoperatively and postoperatively for DVT prophylaxis in patients undergoing subarachnoid hemorrhage (SAH) treatment. Patients with SAH are an understudied population in terms of assessing incidence and impact of HIT. This study aims to investigate the incidence, complications, and outcomes of SAH patients who develop HIT. Methods ICD‐9‐CM and ICD‐10‐CM codes were used to query the National Inpatient Sample for patients with SAH between 2010 and 2019. Subgroup analysis was stratified by HIT development. SAH severity was determined using the National Institute of Health Stroke Scale as a template. Patients from both groups were assessed for baseline clinical characteristics, comorbidities, interventions, complications, and outcomes. Cohorts containing ten or fewer patients must only be described qualitatively. Descriptive statistics, multivariate regressions, and propensity score‐matching were all performed using IBM SPSS 28. Results 76,387 patients were diagnosed with SAH between 2010 and 2019. 166 (.22%) had developed HIT in response to anticoagulant administration. The incidence of HIT was higher in patients who were younger (58.04 vs 61.39, p = 0.01), obese (0.4% vs 0.2%, p &lt; 0.01), on long‐term anticoagulant use (10.84% vs 5.72%, p &lt; 0.01), and had an implanted cerebrospinal fluid drainage device (p &lt; 0.01). Patients with HIT were associated with higher SAH severity (1.42 vs 1.06, p &lt; 0.01). Through both the complete cohort and propensity score‐matched cohort, patients with HIT were associated with higher rates of endovascular coiling, external ventricular drain placement (p &lt; 0.01), and ventriculoperitoneal shunt placement (p &lt; 0.01). HIT patients had significantly higher rates of deep vein thrombosis (p &lt; 0.01), pulmonary embolism (p &lt; 0.01), central venous sinus thrombosis (p = 0.01), pneumonia (p &lt; 0.01), urinary tract infection (p &lt; 0.01), acute kidney injury (p &lt; 0.01), and cerebral vasospasm (p &lt; 0.01). Patients who develop HIT had a longer length of stay (LOS) (24.04 vs 10.48, p &lt; 0.01). HIT continued to be a significant predictor of having an above average LOS (OR: 6.799, CI: 3.985 ‐ 11.6, p &lt; 0.01) when controlling for age, SAH severity, and significant comorbidities. Conclusion Our study revealed that younger SAH patients with various comorbidities are more prone to developing HIT, leading to higher rates of thrombotic events, acute kidney injury, and nosocomial infections, which can significantly prolong their hospital stay. Considering the extended postoperative recovery period for SAH, investigating the causes of HIT can facilitate earlier detection and prevention of thrombotic complications. This nationwide, multicenter, retrospective study provides valuable insights for clinicians on how to prevent and manage HIT in patients with subarachnoid hemorrhage.

Systemic inflammation response index as a clinical outcome evaluating tool and prognostic indicator for hospitalized stroke patients: a systematic review and meta-analysis.

Stroke, which is the main element of cerebrovascular disease (CVD), has become the foremost reason for death and disability on a global scale. The systemic inflammation response index (SIRI), a newly developed and comprehensive indicator, has demonstrated promise in forecasting clinical results for diverse ailments. Nevertheless, the uncertainty surrounding the assessment and prediction of clinical outcomes for stroke patients by SIRI persists, and the conflicting findings from the limited studies conducted on this matter further complicate the situation. Consequently, we performed a thorough systematic review and meta-analysis to explore the correlation between SIRI and the clinical results in individuals suffering from stroke. This research was registered in PROSPERO and carried out following the PRISMA guidelines. A thorough investigation was carried out on PubMed, Embase, the Cochrane Library, Web of Science, and Scopus databases. Furthermore, we conducted a manual search in Chinese databases, such as China national Knowledge Infrastructure (CNKI), WanFang, VIP, and China Biology Medicine (CBM). We assessed the potential for bias in the studies included by utilizing the Newcastle-Ottawa Scale (NOS) tool. Adverse clinical outcomes were the main focus of the study, with secondary endpoints including mortality, the predictive value of SIRI, SIRI values across various endpoints, and clinical parameters associated with subarachnoid hemorrhage (SAH) in relation to low and high SIRI group. Following rigorous evaluation, a grand total of 22 investigations, encompassing a populace of 12,737 individuals, were considered suitable for incorporation in the final analysis. The findings from our meta-analysis indicate a strong and consistent correlation between elevated SIRI levels and adverse functional outcomes, irrespective of the method used to evaluate unfavorable outcomes. Furthermore, increased SIRI values have a strong correlation with mortality rates in both the short and long term. Besides, SIRI is a useful indicator of the severity of SAH. SIRI demonstrates strong predictive ability in identifying unfavorable outcomes and stroke-related pneumonia (SAP), as higher SIRI values are typically linked to negative endpoints. Nevertheless, the meta-analysis indicated that there was no significant increase in the risk of early neurological deterioration (END) and acute hydrocephalus (AHC) in high SIRI group when comparing to low SIRI. This study could potentially pave the way for groundbreaking insights into the relationship between SIRI and stroke patient outcomes, as it appears to be the first meta-analysis to explore this association. Given the critical role of the inflammatory response in stroke recovery, closely monitoring patients with high SIRI levels could represent a promising strategy for mitigating brain damage post-stroke. Thus, further investigation into SIRI and its impact on clinical outcomes is essential. While our initial findings offer valuable insights into this area, continued research is necessary to fully elucidate the potential of SIRI, ideally through dynamic monitoring and large-scale, multi-center studies. Ultimately, this research has the potential to inform clinical decision-making and improve patient outcomes following stroke. https://www.crd.york.ac.uk/prospero/ ; Identifier CRD42023405221.

The role of previous medical history and secondary complications for the outcome of aneurysmal subarachnoid hemorrhage in elderly patients

BackgroundAneurysmal subarachnoid hemorrhage (SAH) presents a devastating diagnosis for elderly individuals, resulting in high morbidity and mortality rates. The aim of the study was to analyze the impact of medical history and complications during SAH on the outcome of elderly patients. MethodsConsecutive SAH cases aged ≥ 65 years old treated in our hospital between 01/2003 and 06/2016 were included (n = 218). Data on comorbidities, previous medication, initial severity, secondary complications, and the outcome were collected. Study endpoints were occurrence of cerebral infarcts, in-hospital mortality, and unfavorable outcome at 6 months after SAH. ResultsCerebral infarcts were documented in 111 (51.2 % ) individuals. Multivariate analysis showed that angiographic vasospasm caused an increase (adjusted odds ratio [aOR] = 3.11, p = 0.022) in the risk of infarction, whereas aspirin treatment decreased (aOR = 0.25, p = 0.001) the risk of infarction. In turn, increasing age (aOR = 1.11, p = 0.002), intracranial hypertension (>20 mmHg, aOR = 3.32, p = 0.006) and acute kidney failure (aOR = 6.65, p = 0.035) during SAH were independently related to the risk of in-hospital mortality (n = 50; 22.9 % ). Finally, patients’ age (aOR = 1.09, p = 0.022), high initial SAH burden (WFNS ≥ 4: aOR = 7.5, p < 0.0001; intraventricular hemorrhage: aOR = 4.38, p = 0.007), aneurysm clipping (aOR = 4.07, p = 0.018), and intracranial hypertension during SAH (aOR = 4.08, p = 0.006) were independent predictors of unfavorable outcome (n = 106/192; 55.5 % ). Previous medical history showed no negative impact on the severity, course and outcome of SAH. ConclusionAbout half of elderly SAH patients face poor outcomes after aneurysm securing. The initial severity of and complications during SAH are the major contributors to poor treatment results. Our findings might help to optimize the treatment strategies.

Effect of Intrathecal Urokinase Infusion on Cerebral Vasospasm After Aneurysmal Subarachnoid Hemorrhage

Vasospasm following an aneurysmal subarachnoid hemorrhage (SAH) causes serious neurological complications, despite surgical clipping of the aneurysm. Intrathecal urokinase (UK) infusion has been shown to effectively prevent symptomatic vasospasm in patients who have undergone endovascular obliteration of the ruptured aneurysms. To investigate whether intrathecal UK infusion can prevent symptomatic vasospasm in patients undergoing surgical or endovascular treatment. A total of 90 patients with severe aneurysmal SAH were enrolled and assigned to a surgical neck clipping (n= 56) or an endovascular coil embolization (n= 34) groups. After treatment, UK infusion from the lumbar drain was repeated in 32 patients in the surgical neck clipping group (group B) and all in the endovascular coil embolization group (group C) until complete resolution of the SAH was observed on computed tomography. The remaining 24 of the surgical neck clipping group, without UK infusion, were assigned to group A. Symptomatic vasospasm occurred in 7 (29.2%) patients in group A, 2 (6.3%) in group B, and none in group C (group A vs. group B [P=0.02]; group B vs. group C [P=0.14]). Excellent clinical outcomes (modified Rankin score, 0 or 1) were observed in 37.5%, 59.4%, and 76.5% of patients in group A, B, and C, respectively (group A vs. group B [P=0.11]). Clearance of SAH via intrathecal UK infusion significantly reduced symptomatic vasospasm in patients in both UK groups, resulting in better clinical outcomes.

Early brain metabolic disturbances associated with delayed cerebral ischemia in patients with severe subarachnoid hemorrhage

Delayed cerebral ischemia (DCI) is a devastating complication of aneurysmal subarachnoid hemorrhage (ASAH) causing brain infarction and disability. Cerebral microdialysis (CMD) monitoring is a focal technique that may detect DCI-related neurochemical changes as an advance warning. We conducted retrospective analyses from 44 poor-grade ASAH patients and analyzed glucose, lactate, pyruvate, and glutamate concentrations in control patients without DCI (n = 19), and in patients with DCI whose CMD probe was located within (n = 17) or outside (n = 8) a new infarct. When monitored from within a lesion, DCI was preceded by a decrease in glucose and a surge in glutamate, accompanied by increases in lactate/pyruvate and lactate/glucose ratios whereas these parameters remained stable in control patients. When CMD monitoring was performed outside the lesion, the glutamate surge was absent, but glucose and L/G ratio were still significantly altered. Overall, glucose and L/G ratio were significant biomarkers of DCI (se96.0, spe73.7-68.4). Glucose and L/G predicted DCI 67 h before CT detection of a new infarct. The pathogenesis of DCI therefore induces early metabolic disturbances that can be detected by CMD as an advance warning. Glucose and L/G could provide a trigger for initiating further examination or therapy, earlier than when guided by other monitoring techniques.

Balanced volatile sedation with isoflurane in critically ill patients with aneurysmal subarachnoid hemorrhage - a retrospective observational study.

In patients with severe aneurysmal subarachnoid hemorrhage (SAH) deep sedation is often used early in the course of the disease in order to control brain edema formation and thus intracranial hypertension. However, some patients do not reach an adequate sedation depth despite high doses of common intravenous sedatives. Balanced sedation protocols incorporating low-dose volatile isoflurane administration might improve insufficient sedation depth in these patients. We retrospectively analyzed ICU patients with severe aneurysmal SAH who received isoflurane in addition to intravenous anesthetics in order to improve insufficient sedation depth. Routinely recorded data from neuromonitoring, laboratory and hemodynamic parameters were compared before and up to 6 days after initiation of isoflurane. Sedation depth measured using the bispectral index improved in thirty-six SAH patients (-15.16; p = 0.005) who received additional isoflurane for a mean period of 9.73 ± 7.56 days. Initiation of isoflurane sedation caused a decline in mean arterial pressure (-4.67 mmHg; p = 0.014) and cerebral perfusion pressure (-4.21 mmHg; p = 0.013) which had to be balanced by increased doses of vasopressors. Patients required increased minute ventilation in order to adjust for the increase in PaCO2 (+2.90 mmHg; p < 0.001). We did not detect significant increases in mean intracranial pressure. However, isoflurane therapy had to be terminated prematurely in 25% of the patients after a median of 30 h due to episodes of intracranial hypertension or refractory hypercapnia. A balanced sedation protocol including isoflurane is feasible for SAH patients experiencing inadequately shallow sedation. However, therapy should be restricted to patients without impaired lung function, hemodynamic instability and impending intracranial hypertension.

Retracted: High-Quality Nursing Combined with the Whole-Course Responsibility Nursing Intervention Reduces the Incidence of Complications in Severe Aneurysmal Subarachnoid Hemorrhage.

[This retracts the article DOI: 10.1155/2022/3252718.].

Pretreatment with Clodronate Improved Neurological Function by Preventing Reduction of Posthemorrhagic Cerebral Blood Flow in Experimental Subarachnoid Hemorrhage.

Brain perivascular macrophages (PVMs) are potential treatment targets for subarachnoid hemorrhage (SAH), and previous studies revealed that their depletion by clodronate (CLD) improved outcomes after experimental SAH. However, the underlying mechanisms are not well understood. Therefore, we investigated whether reducing PVMs by CLD pretreatment improves SAH prognosis by inhibiting posthemorrhagic impairment of cerebral blood flow (CBF). In total, 80 male Sprague-Dawley rats received an intracerebroventricular injection of the vehicle (liposomes) or CLD. Subsequently, the rats were categorized into the prechiasmatic saline injection (sham) and blood injection (SAH) groups after 72h. We assessed its effects on weak and severe SAH, which were induced by 200- and 300-µL arterial blood injections, respectively. In addition, neurological function at 72h and CBF changes from before the intervention to 5min after were assessed in rats after sham/SAH induction as the primary and secondary end points, respectively. CLD significantly reduced PVMs before SAH induction. Although pretreatment with CLD in the weak SAH group provided no additive effects on the primary end point, rats in the severe SAH group showed significant improvement in the rotarod test. In the severe SAH group, CLD inhibited acute reduction of CBF and tended to decrease hypoxia-inducible factor 1α expression. Furthermore, CLD reduced the number of PVMs in rats subjected to sham and SAH surgery, although no effects were observed in oxidative stress and inflammation. Our study proposes that pretreatment with CLD-targeting PVMs can improve the prognosis of severe SAH through a candidate mechanism of inhibition of posthemorrhagic CBF reduction.

Cisterna Magna Injection Mouse Model of Subarachnoid Hemorrhage (SAH): A Systematic Literature Review of Preclinical SAH Research

Objective: This review article describes the characteristics of published literature using the cisterna magna blood injection mouse model of subarachnoid hemorrhage (SAH) with the aim to define particular standards and identify moderators of mortality rate, SAH grade, and large artery vasospasm. Methods: We searched for English-original peer-reviewed studies which reported the induction of SAH in mice via single or multiple blood injections into the cisterna magna. The search included studies published until 13th February 2023 on PubMed, Embase and Web of Science. Furthermore, we investigated the reporting of mortality rate, vasospasms by measuring large arteries, and SAH grade in cisterna magna blood injection mouse model. Results: Seven articles out of 136 identified records matched our inclusion criteria and were therefore included in descriptive analysis. Four articles reported the mortality rate which varied between zero and 22 percent. Five articles displayed vasospasms of large cerebral arteries including basilar artery (BA), anterior cerebral artery (ACA), and middle cerebral artery (MCA). Interestingly, the diameters of the observed arteries started to decrease already within the first hour after blood injection and achieved the lowest values at different times, but mainly between six and twelve hours after SAH induction. The artery diameters reached nearly their pre-SAH (control group) diameters approximately after four to seven days after SAH. However, the SAH severity grade was reported in none of these publications. No uniform model characteristics were observed in current literature. Conclusion: A systemic overview of the cisterna magna blood injection mouse model of SAH is presented. An important heterogeneity was observed. Hence, standardized model features and study endpoints have to be defined in order to improve reporting frequency and quality to enhance the reproducibility of preclinical SAH research in the future.

Aneurysmal Subarachnoid Hemorrhage in Hospitalized Patients on Anticoagulants—A Two Center Matched Case-Control Study

Objective-Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods-Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results-During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4-5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1-3) after 12 months. Conclusions-Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients.