Anesthesia modality does not affect clinical outcomes of intra-arterial vasodilator treatment in patients with symptomatic cerebral vasospasms

Background: Delayed cerebral ischemia and cerebral vasospasm remain the leading causes of poor outcome in survivors of aneurysmal subarachnoid hemorrhage. Refractory cerebral vasospasms can be treated with endovascular vasodilator therapy, which can either be performed in conscious sedation or general anesthesia. The aim of this study is to compare the effect of the anesthesia modality on long-term clinical outcomes in patients undergoing endovascular vasodilator therapy due to cerebral vasospasm and hypoperfusion. Methods: Modified Rankin Scale (mRS) scores were retrospectively analyzed at time of discharge from the hospital and six months after aneurysmal subarachnoid hemorrhage. Additionally, National Institutes of Health Stroke Scale (NIHSS) was assessed 24 hours before, immediately before, immediately after, and 24 hours after endovascular vasodilator therapy, and at discharge and six months. Interventional parameters such as duration of intervention, choice and dosage of vasodilator and number of arteries treated were also recorded. Results: A total of 98 patients were included in this analysis and separated into patients who had interventions in conscious sedation, general anesthesia and a mix of both. Neither mRS at discharge nor at six months showed a significant difference for functionally independent outcomes (mRS 0-2) between groups. NIHSS before endovascular vasodilator therapy was significantly higher in patients receiving interventions in general anesthesia but did not differ anymore between groups six months after the initial bleed. Conclusion: This study did not observe a difference in outcome whether patients underwent endovascular vasodilator therapy in general anesthesia or conscious sedation for refractory cerebral vasospasms. Hence, the choice should be made for each patient individually.

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Anesthesia modality does not affect clinical outcomes of intra-arterial vasodilator treatment in patients with symptomatic cerebral vasospasms

F1000Research ◽

10.12688/f1000research.52324.2 ◽

2021 ◽

Vol 10 ◽

pp. 417

Author(s):

Corinne Fischer ◽

Sonja Vulcu ◽

Johannes Goldberg ◽

Franca Wagner ◽

Belén Rodriguez ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

General Anesthesia ◽

Clinical Outcomes ◽

Cerebral Vasospasm ◽

Conscious Sedation ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Vasodilator Therapy ◽

Significant Difference ◽

Vasodilator Treatment

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Cerebrospinal fluid macrophage migration inhibitory factor: a potential predictor of cerebral vasospasm and clinical outcome after aneurysmal subarachnoid hemorrhage

Journal of Neurosurgery ◽

10.3171/2019.6.jns19613 ◽

2020 ◽

Vol 133 (6) ◽

pp. 1786-1791 ◽

Cited By ~ 1

Author(s):

Kevin Kwan ◽

Orseola Arapi ◽

Katherine E. Wagner ◽

Julia Schneider ◽

Heustein L. Sy ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Vasospasm ◽

Migration Inhibitory Factor ◽

Macrophage Migration Inhibitory Factor ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Inhibitory Factor ◽

Macrophage Migration ◽

Significant Difference

OBJECTIVEIn patients with aneurysmal subarachnoid hemorrhage (aSAH), poor outcomes have been shown to be correlated with subsequent cerebral vasospasm (CV) and delayed cerebral ischemia (DCI). The identification of novel biomarkers may aid in the prediction of which patients are vulnerable to developing vasospasm, cerebral ischemia, and neurological deterioration.METHODSIn this prospective clinical study at North Shore University Hospital, patients with aSAH or normal pressure hydrocephalus (NPH) with external ventricular drains were enrolled. The concentration of macrophage migration inhibitory factor (MIF) in CSF was assessed for correlation with CV or DCI, the primary outcome measures.RESULTSTwenty-five patients were enrolled in the aSAH group and 9 were enrolled in the NPH group. There was a significant increase in aggregate CSF MIF concentration in patients with aSAH versus those with NPH (24.4 ± 19.2 vs 2.3 ± 1.1 ng/ml, p < 0.0002). Incidence of the day of peak MIF concentration significantly correlated with the onset of clinical vasospasm (rho = 0.778, p < 0.0010). MIF concentrations were significantly elevated in patients with versus those without evidence of DCI (18.7 ± 4.93 vs 8.86 ± 1.28 ng/ml, respectively, p < 0.0025). There was a significant difference in MIF concentrations between patients with infection versus those without infection (16.43 ± 4.21 vs 8.5 ± 1.22 ng/ml, respectively, p < 0.0119).CONCLUSIONSPreliminary evidence from this study suggests that CSF concentrations of MIF are correlated with CV and DCI. These results, however, could be confounded in the presence of clinical infection. A study with a larger patient sample size is necessary to corroborate these findings.

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Computed tomography perfusion imaging after aneurysmal subarachnoid hemorrhage can detect cerebral vasospasm and predict delayed cerebral ischemia after endovascular treatment

Surgical Neurology International ◽

10.25259/sni_14_2020 ◽

2020 ◽

Vol 11 ◽

pp. 233

Author(s):

Koji Omoto ◽

Ichiro Nakagawa ◽

Fumihiko Nishimura ◽

Shuichi Yamada ◽

Yasushi Motoyama ◽

...

Keyword(s):

Computed Tomography ◽

Subarachnoid Hemorrhage ◽

Endovascular Treatment ◽

Clinical Outcomes ◽

Cerebral Vasospasm ◽

Cerebral Blood Volume ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Mean Transit Time ◽

Delayed Cerebral Ischemia ◽

Computed Tomography Perfusion

Background: Endovascular treatment (ET) can improve angiographic cerebral vasospasm (CV) after aneurysmal subarachnoid hemorrhage, but was unrelated to clinical outcomes in previous analyses. Appropriate detection of CV and precise indications for ET are required. This study investigated whether changes in computed tomography perfusion (CTP) parameter can determine indications for ET in CV and predict its effectiveness. Methods: Participants comprised 140 patients who underwent neck clipping or coil embolization. CTP was performed a week after aneurysmal treatment or when clinical deterioration had occurred. Patients were divided into ET and non-ET groups by propensity score matching. In addition, the ET group was divided into subgroups with and without new cerebral infarction (CI). All CTP images in the three groups were retrospectively investigated qualitatively and quantitatively. CI was diagnosed from CT at 3 months postoperatively. Results: Of the 121 patients examined, 15 patients (11%) needed ET. In qualitative analysis, all ET group patients displayed extension of time-to-peak (TTP) at the region of vasospastic change, regardless of the presence of CI. Quantitative analysis showed significant decreases in cerebral blood volume (P < 0.01), cerebral blood flow (CBF) (P < 0.001), and extension in TTP (P < 0.01) in the ET group compared with the non-ET group. A significant decrease in CBF (P < 0.001) and extension in mean transit time (P < 0.001) was seen in the ET with CI subgroup compared with the ET without CI subgroup. Conclusion: CTP in the vasospastic period may be an indication for ET and predict the effectiveness of ET for CV to improve clinical outcomes.

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Blood free Radicals Concentration Determined by Electron Paramagnetic Resonance Spectroscopy and Delayed Cerebral Ischemia Occurrence in Patients with Aneurysmal Subarachnoid Hemorrhage

Cell Biochemistry and Biophysics ◽

10.1007/s12013-017-0820-7 ◽

2017 ◽

Vol 75 (3-4) ◽

pp. 351-358 ◽

Cited By ~ 2

Author(s):

Grzywna Ewelina ◽

Stachura Krzysztof ◽

Moskala Marek ◽

Kruczala Krzysztof

Keyword(s):

Electron Paramagnetic Resonance ◽

Free Radicals ◽

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Paramagnetic Resonance ◽

Significant Difference ◽

Electron Paramagnetic

Abstract Pathophysiology of delayed cerebral ischemia and cerebral vasospasm following aneurysmal subarachnoid hemorrhage is still poorly recognized, however free radicals are postulated as one of the crucial players. This study was designed to scrutinize whether the concentration of free radicals in the peripheral venous blood is related to the occurrence of delayed cerebral ischemia associated with cerebral vasospasm. Twenty-four aneurysmal subarachnoid hemorrhage patients and seven patients with unruptured intracranial aneurysm (control group) have been studied. Free radicals in patients’ blood have been detected by the electron paramagnetic resonance (CMH.HCl spin probe, 150 K, ELEXSYS E500 spectrometer) on admission and at least 72 h from disease onset. Delayed cerebral ischemia monitoring was performed by daily neurological follow-up and transcranial color coded Doppler. Delayed cerebral ischemia observed in six aneurysmal subarachnoid hemorrhage patients was accompanied by cerebral vasospasm in all six cases. No statistically significant difference in average free radicals concentration between controls and study subgroups was noticed on admission (p = .3; Kruskal–Wallis test). After 72 h free radicals concentration in delayed cerebral ischemia patients (3.19 ± 1.52 mmol/l) differed significantly from the concentration in aneurysmal subarachnoid hemorrhage patients without delayed cerebral ischemia (0.65 ± 0.37 mmol/l) (p = .012; Mann–Whitney test). These findings are consistent with our assumptions and seem to confirm the role of free radicals in delayed cerebral ischemia development. Preliminary results presented above are promising and we need perform further investigation to establish whether blood free radicals concentration may serve as the biomarker of delayed cerebral ischemia associated with cerebral vasospasm.

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Severity of cerebral vasospasm associated with development of collaterals following aneurysmal subarachnoid hemorrhage

Journal of NeuroInterventional Surgery ◽

10.1136/neurintsurg-2017-013410 ◽

2018 ◽

Vol 10 (7) ◽

pp. 638-643

Author(s):

Fawaz Al-Mufti ◽

Jens Witsch ◽

Nathan Manning ◽

Michael Crimmins ◽

Krishna Amuluru ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Delayed Cerebral Ischemia ◽

Weighted Kappa ◽

Observational Cohort Study ◽

Cognitive Outcome ◽

Multivariable Model ◽

Final Infarct Size ◽

Observational Cohort

IntroductionCerebral collateral circulation has been studied extensively in ischemic stroke where it has been shown to be a predictor of reperfusion, final infarct size, and outcome. Little is known about the significance of the collaterals in the setting of aneurysmal subarachnoid hemorrhage (aSAH). We sought to evaluate the effect of cerebral vasospasm on the development of cerebral collaterals following aneurysmal subarachnoid hemorrhage and the effects of the latter on delayed cerebral ischemia (DCI).MethodsWe retrospectively evaluated 64 aSAH patients with evidence of DCI between day 5 and 7, enrolled in a prospectively maintained observational cohort study. Angiograms were evaluated by four blinded neurointerventionalists. We compared good collateral grades to poor collateral grades, additionally we compared enrolled individuals with any collaterals versus patients who had no collaterals.ResultsInter-rater reliability for collateral grades was substantial (weighted kappa 0.632). Mild vasospasm was more frequent in patients with poor collateral grades compared with patients with good collateral grades (32% vs 4% P=0.012). There was no difference between the collateral groups with regards to DCI, functional, or cognitive outcome. Patients adjudicated to have any collaterals were more likely to have severe vasospasm (62% vs 33% P=0.023) and less likely to have mild vasospasm (37% vs 9% P=0.007). In a multivariable model, vasospasm severity remained associated with collateral status, while aneurysm location was not.ConclusionsThe severity of vasospasm following aSAH was associated with the development of collaterals. There was no difference between collateral grades with regards to DCI or outcome.

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Meta-analysis of associations of genetic polymorphisms with cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage

Acta Neurologica Belgica ◽

10.1007/s13760-021-01829-5 ◽

2021 ◽

Author(s):

Yuliia Solodovnikova ◽

Alina Ivaniuk ◽

Tetiana Marusich ◽

Anatoliy Son

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Ischemia ◽

Genetic Polymorphisms ◽

Cerebral Vasospasm ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Meta Analysis ◽

Delayed Cerebral Ischemia

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Abstract T P352: Dantrolene for the Prevention and Treatment of Cerebral Vasospasm after Subarachnoid Hemorrhage - A Randomized Placebo-Controlled Trial to Assess Safety, Tolerability and Feasibility

Stroke ◽

10.1161/str.45.suppl_1.tp352 ◽

2014 ◽

Vol 45 (suppl_1) ◽

Author(s):

Susanne Muehlschlegel ◽

Raphael Carandang ◽

Wiley Hall ◽

Kini Nisha ◽

Saef Izzy ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Cerebral Vasospasm ◽

Liver Toxicity ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Statistical Significance ◽

Delayed Cerebral Ischemia ◽

Double Blind ◽

Outcome Differences ◽

Infusion Period

Introduction: Dantrolene is neuroprotective in animal models and may attenuate cerebral vasospasm (cVSP) after aneurysmal subarachnoid hemorrhage (aSAH) in humans. We evaluated safety/tolerability and feasibility of intravenous dantrolene (IV-D) after aSAH. Methods: In this single-center, randomized, double-blind, placebo-controlled trial, 31 patients with acute aSAH were randomized to IV-D 1.25 mg IV every 6 hours x 7 days (n=16) or placebo (n=15). Primary endpoint was incidence of hyponatremia (sNa ≤ 134 mmol/L) and liver toxicity (% patients with ALT, AST and AlkPhos >5x upper limit of normal). Secondary safety endpoints included tolerability, systemic hypotension and intracranial hypertension. Efficacy was explored by clinical, transcranial Doppler (TCD) or angiographic cVSP occurrence, delayed cerebral ischemia (DCI) and 3-month modified-Rankin-Scale, Glasgow Outcome Scale and Barthel Index. Statistical analysis was performed using non-parametric tests, generalized estimating equations and mixed models. Results: Between IV-D vs. placebo, no differences were observed in the primary outcome (hyponatremia: 44% vs. 67% [p=0.29]; liver toxicity 6% vs. 0% [p=1.0]). Numerically more AEs and SAEs were seen in the IV-D group, but did not reach statistical significance (16 vs. 5 AEs, of which 5 vs. 2 were severe; RR 2.2; 95% CI 0.7-6.7; p=0.16). Three IV-D vs. two placebo patients reached stop criteria: one IV-D patient developed liver toxicity; two patients in each group developed brain edema requiring osmotherapy. No differences in angiographic, TCD, clinical cVSP, DCI, or 3-month functional outcomes were seen. Quantitative angiogram analysis revealed a trend towards increased vessel diameters in the IV-D group after the 7-day infusion-period (p=0.05). Conclusion: In this small trial, IV-Dantrolene after aSAH was feasible, tolerable and safe, but was underpowered to show efficacy or outcome differences.

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Randomized, placebo-controlled, double-blind, pilot trial to investigate safety and efficacy of Cerebrolysin in patients with aneurysmal subarachnoid hemorrhage

BMC Neurology ◽

10.1186/s12883-020-01908-9 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Peter Y. M. Woo ◽

Joanna W. K. Ho ◽

Natalie M. W. Ko ◽

Ronald P. T. Li ◽

Leo Jian ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Adverse Effects ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Pilot Trial ◽

Delayed Cerebral Ischemia ◽

Trial Registration ◽

Study Group ◽

Double Blind ◽

Link Type ◽

Significant Difference

Asbtract Background There are limited neuroprotective treatment options for patients with aneurysmal subarachnoid hemorrhage (SAH). Cerebrolysin, a brain-specific proposed pleiotropic neuroprotective agent, has been suggested to improve global functional outcomes in ischemic stroke. We investigated the efficacy, safety and feasibility of administering Cerebrolysin for SAH patients. Methods This was a prospective, randomized, double-blind, placebo-controlled, single-center, parallel-group pilot study. Fifty patients received either daily Cerebrolysin (30 ml/day) or a placebo (saline) for 14 days (25 patients per study group). The primary endpoint was a favorable Extended Glasgow Outcome Scale (GOSE) of 5 to 8 (moderate disability to good recovery) at six-months. Secondary endpoints included the modified Ranking Scale (mRS), the Montreal Cognitive Assessment (MOCA) score, occurrence of adverse effects and the occurrence of delayed cerebral ischemia (DCI). Results No severe adverse effects or mortality attributable to Cerebrolysin were observed. No significant difference was detected in the proportion of patients with favorable six-month GOSE in either study group (odds ratio (OR): 1.49; 95% confidence interval (CI): 0.43–5.17). Secondary functional outcome measures for favorable six-month recovery i.e. a mRS of 0 to 3 (OR: 3.45; 95% CI 0.79–15.01) were comparable for both groups. Similarly, there was no difference in MOCA neurocognitive performance (p-value: 0.75) and in the incidence of DCI (OR: 0.85 95% CI: 0.28–2.59). Conclusions Use of Cerebrolysin in addition to standard-of-care management of aneurysmal SAH is safe, well tolerated and feasible. However, the neutral results of this trial suggest that it does not improve the six-month global functional performance of patients. Clinical trial registration Name of Registry: ClinicalTrials.gov Trial Registration Number: NCT01787123. Date of Registration: 8th February 2013.

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Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage

Neurology ◽

10.1212/wnl.0000000000007862 ◽

2019 ◽

Vol 93 (5) ◽

pp. e458-e466 ◽

Cited By ~ 13

Author(s):

Ramazan Jabbarli ◽

Daniela Pierscianek ◽

Roland Rölz ◽

Marvin Darkwah Oppong ◽

Klaus Kaier ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Functional Outcome ◽

Cerebral Vasospasm ◽

Delayed Cerebral Ischemia ◽

Final Analysis ◽

Unfavorable Outcome ◽

Independent Effect ◽

Preventive Strategy ◽

Class Iii ◽

Significant Difference

ObjectiveDelayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts.MaterialsData from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed.ResultsThe final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], p < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, p < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, p = 0.0001) and unfavorable outcome (44% vs 50.6%, p = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome.ConclusionsA preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH.Classification of evidenceThis study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.

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High-Dose Nadroparin Following Endovascular Aneurysm Treatment Benefits Outcome After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽

10.1093/neuros/nyx381 ◽

2017 ◽

Vol 83 (2) ◽

pp. 281-287 ◽

Cited By ~ 1

Author(s):

Rene Post ◽

IJsbrand A.J Zijlstra ◽

Rene van den Berg ◽

Bert A Coert ◽

Dagmar Verbaan ◽

...

Keyword(s):

Subarachnoid Hemorrhage ◽

Dose Group ◽

Low Dose ◽

Aneurysmal Subarachnoid Hemorrhage ◽

Controlled Trial ◽

Delayed Cerebral Ischemia ◽

Neurological Status ◽

High Dose ◽

Aneurysm Treatment ◽

Significant Difference

Abstract BACKGROUND Delayed cerebral ischemia (DCI) is one of the major causes of delayed morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To evaluate the effect of high-dose nadroparin treatment following endovascular aneurysm treatment on the occurrence of DCI and clinical outcome. METHODS Medical records of 158 adult patients with an aSAH were retrospectively analyzed. Those patients treated endovascularly for their ruptured aneurysm were included in this study. They received either high-dose (twice daily 5700 AxaIE) or low-dose (once daily 2850 AxaIE) nadroparin treatment after occlusion of the aneurysm. Medical charts were reviewed and imaging was scored by 2 independent neuroradiologists. Data with respect to in-hospital complications, peri-procedural complications, discharge location, and mortality were collected. RESULTS Ninety-three patients had received high-dose nadroparin, and 65 patients prophylactic low-dose nadroparin. There was no significant difference in clinical DCI occurrence between patients treated with high-dose (34%) and low-dose (31%) nadroparin. More patients were discharged to home in patients who received high-dose nadroparin (40%) compared to low-dose (17%; odds ratio [OR] 3.13, 95% confidence interval [95% CI]: 1.36-7.24). Furthermore, mortality was lower in the high-dose group (5%) compared to the low-dose group (23%; OR 0.19, 95% CI: 0.07-0.55), also after adjusting for neurological status on admission (OR 0.21, 95% CI: 0.07-0.63). CONCLUSION Patients who were treated with high-dose nadroparin after endovascular treatment for aneurysmal SAH were more often discharged to home and showed lower mortality. High-dose nadroparin did not, however, show a decrease in the occurrence of clinical DCI after aSAH. A randomized controlled trial seems warranted.

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