scholarly journals Conditioning Effect of Inhalational Anesthetics on Delayed Cerebral Ischemia After Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2020 ◽  
Author(s):  
Umeshkumar Athiraman ◽  
Rajat Dhar ◽  
Keshav Jayaraman ◽  
Menelaos Karanikolas ◽  
Daniel Helsten ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Protective Effect ◽  
Neurological Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Angiographic Vasospasm ◽  
Inhalational Anesthetic

Abstract BACKGROUND Delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) has been identified as an independent predictor of poor outcome in numerous studies. OBJECTIVE To investigate the potential protective role of inhalational anesthetics against angiographic vasospasm, DCI, and neurologic outcome in SAH patients. METHODS After Institutional Review Board approval, data were collected retrospectively for SAH patients who received general anesthesia for aneurysm repair between January 1st, 2010 and May 31st, 2018. Primary outcomes were angiographic vasospasm, DCI, and neurologic outcome as measured by modified Rankin scale at hospital discharge. Univariate and logistic regression analysis were performed to identify independent predictors of these outcomes. RESULTS The cohort included 390 SAH patients with an average age of 56 ± 15 (mean ± SD). Multivariate logistic regression analysis identified inhalational anesthetic only technique, Hunt-Hess grade, age, anterior circulation aneurysm and average intraoperative mean blood pressure as independent predictors of angiographic vasospasm. Inhalational anesthetic only technique and modified Fishers grade were identified as independent predictors of DCI. No impact on neurological outcome at time of discharge was noted. CONCLUSION Our data provide additional evidence that inhalational anesthetic conditioning in SAH patients affords protection against angiographic vasospasm and new evidence that it exerts a protective effect against DCI. When coupled with similar results from preclinical studies, our data suggest further investigation into the impact of inhalational anesthetic conditioning on SAH patients, including elucidating the most effective dosing regimen, defining the therapeutic window, determining whether a similar protective effect against early brain injury, and on long-term neurological outcome exists.

scholarly journals Ultra-early angiographic vasospasm associated with delayed cerebral ischemia and infarction following aneurysmal subarachnoid hemorrhage

2017 ◽  
Vol 126 (5) ◽  
pp. 1545-1551 ◽  
Author(s):  
Fawaz Al-Mufti ◽  
David Roh ◽  
Shouri Lahiri ◽  
Emma Meyers ◽  
Jens Witsch ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Cerebral Infarction ◽  
Functional Outcome ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Angiographic Vasospasm ◽  
Increased Risk ◽  
Address Data

OBJECTIVEThe clinical significance of cerebral ultra-early angiographic vasospasm (UEAV), defined as cerebral arterial narrowing within the first 48 hours of aneurysmal subarachnoid hemorrhage (aSAH), remains poorly characterized. The authors sought to determine its frequency, predictors, and impact on functional outcome.METHODSThe authors prospectively studied UEAV in a cohort of 1286 consecutively admitted patients with aSAH between August 1996 and June 2013. Admission clinical, radiographic, and acute clinical course information was documented during patient hospitalization. Functional outcome was assessed at 3 months using the modified Rankin Scale. Logistic regression and Cox proportional hazards models were generated to assess predictors of UEAV and its relationship to delayed cerebral ischemia (DCI) and outcome. Multiple imputation methods were used to address data lost to follow-up.RESULTSThe cohort incidence rate of UEAV was 4.6%. Multivariable logistic regression analysis revealed that younger age, sentinel bleed, and poor admission clinical grade were significantly associated with UEAV. Patients with UEAV had a 2-fold increased risk of DCI (odds ratio [OR] 2.3, 95% confidence interval [CI] 1.4–3.9, p = 0.002) and cerebral infarction (OR 2.0, 95% CI 1.0–3.9, p = 0.04), after adjusting for known predictors. Excluding patients who experienced sentinel bleeding did not change this effect. Patients with UEAV also had a significantly higher hazard for DCI in a multivariable model. UEAV was not found to be significantly associated with poor functional outcome (OR 0.8, 95% CI 0.4–1.6, p = 0.5).CONCLUSIONSUEAV may be less frequent than has been reported previously. Patients who exhibit UEAV are at higher risk for refractory DCI that results in cerebral infarction. These patients may benefit from earlier monitoring for signs of DCI and more aggressive treatment. Further study is needed to determine the long-term functional significance of UEAV.

Evidence for a conditioning effect of inhalational anesthetics on angiographic vasospasm after aneurysmal subarachnoid hemorrhage

2020 ◽  
Vol 133 (1) ◽  
pp. 152-158 ◽  
Author(s):  
Umeshkumar Athiraman ◽  
Diane Aum ◽  
Ananth K. Vellimana ◽  
Joshua W. Osbun ◽  
Rajat Dhar ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Brain Injury ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Multivariate Logistic Regression Analysis ◽  
Secondary Brain Injury ◽  
Large Artery ◽  
Inhalational Anesthetics ◽  
Angiographic Vasospasm ◽  
Inhalational Anesthetic

OBJECTIVEDelayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) is characterized by large-artery vasospasm, distal autoregulatory dysfunction, cortical spreading depression, and microvessel thrombi. Large-artery vasospasm has been identified as an independent predictor of poor outcome in numerous studies. Recently, several animal studies have identified a strong protective role for inhalational anesthetics against secondary brain injury after SAH including DCI—a phenomenon referred to as anesthetic conditioning. The aim of the present study was to assess the potential role of inhalational anesthetics against cerebral vasospasm and DCI in patients suffering from an SAH.METHODSAfter IRB approval, data were collected retrospectively for all SAH patients admitted to the authors’ hospital between January 1, 2010, and December 31, 2013, who received general anesthesia with either inhalational anesthetics only (sevoflurane or desflurane) or combined inhalational (sevoflurane or desflurane) and intravenous (propofol) anesthetics during aneurysm treatment. The primary outcomes were development of angiographic vasospasm and development of DCI during hospitalization. Univariate and logistic regression analyses were performed to identify independent predictors of these endpoints.RESULTSThe cohort included 157 SAH patients whose mean age was 56 ± 14 (± SD). An inhalational anesthetic–only technique was employed in 119 patients (76%), while a combination of inhalational and intravenous anesthetics was employed in 34 patients (22%). As expected, patients in the inhalational anesthetic–only group were exposed to significantly more inhalational agent than patients in the combination anesthetic group (p < 0.05). Multivariate logistic regression analysis identified inhalational anesthetic–only technique (OR 0.35, 95% CI 0.14–0.89), Hunt and Hess grade (OR 1.51, 95% CI 1.03–2.22), and diabetes (OR 0.19, 95% CI 0.06–0.55) as significant predictors of angiographic vasospasm. In contradistinction, the inhalational anesthetic–only technique had no significant impact on the incidence of DCI or functional outcome at discharge, though greater exposure to desflurane (as measured by end-tidal concentration) was associated with a lower incidence of DCI.CONCLUSIONSThese data represent the first evidence in humans that inhalational anesthetics may exert a conditioning protective effect against angiographic vasospasm in SAH patients. Future studies will be needed to determine whether optimized inhalational anesthetic paradigms produce definitive protection against angiographic vasospasm; whether they protect against other events leading to secondary brain injury after SAH, including microvascular thrombi, autoregulatory dysfunction, blood-brain barrier breakdown, neuroinflammation, and neuronal cell death; and, if so, whether this protection ultimately improves patient outcome.

Predictors of Delayed Cerebral Ischemia in Patients with Aneurysmal Subarachnoid Hemorrhage with Asymptomatic Angiographic Vasospasm on Admission

2017 ◽  
Vol 97 ◽  
pp. 199-204 ◽  
Author(s):  
Abdulrahman Aldakkan ◽  
Alireza Mansouri ◽  
Blessing N.R. Jaja ◽  
Naif M. Alotaibi ◽  
R. Loch Macdonald ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Angiographic Vasospasm

Gain-of-function polymorphisms of cystathionine β-synthase and delayed cerebral ischemia following aneurysmal subarachnoid hemorrhage

2011 ◽  
Vol 115 (1) ◽  
pp. 101-107 ◽  
Author(s):  
Bartosz T. Grobelny ◽  
Andrew F. Ducruet ◽  
Peter A. DeRosa ◽  
Ivan S. Kotchetkov ◽  
Brad E. Zacharia ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Intracellular Signaling ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Gain Of Function ◽  
Functional Polymorphisms ◽  
Angiographic Vasospasm ◽  
Serum Homocysteine ◽  
Buccal Swabs

Object Cystathionine β-synthase (CBS) is an enzyme that metabolizes homocysteine to form H2S in the brain. Hydrogen sulfide functions as a vasodilator as well as a regulator of neuronal ion channels and multiple intracellular signaling pathways. Given the myriad effects of H2S, the authors hypothesized that patients possessing gain-of-function polymorphisms of the CBS gene will experience a decreased incidence of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH). Methods Patients were enrolled in a prospective observational database of aSAH outcomes. DNA was extracted from buccal swabs and sequenced for 3 functional polymorphisms of the CBS gene (699C→T, 844ins68, and 1080C→T) by polymerase chain reaction. Serum homocysteine levels (μmol/L) were assayed. Multivariate analysis was used to determine the relationship between CBS genotype and occurrence of both angiographic vasospasm and DCI. Results There were 87 patients included in the study. None of the polymorphisms investigated were significantly associated with the incidence of angiographic vasospasm. However, after controlling for admission hypertension, patients with the gain-of-function 844 WT/ins genotypes were less likely to experience DCI relative to those with the 844 WT/WT genotype (86 patients, p = 0.050), while the decrease-in-function genotype 1080 TT was more likely to experience DCI relative to those with 1080 CC and CT genotypes (84 patients, p = 0.042). Serum homocysteine levels did not correlate with the extent of either angiographic vasospasm or DCI in this analysis. Conclusions Polymorphisms of the CBS gene that impart gain-of-function may be associated with a reduced risk of DCI after aSAH, independent of serum homocysteine. Signaling through H2S may mediate protection from DCI following aSAH through a mechanism that does not involve macrovascular vasodilation.

scholarly journals Delayed Cerebral Ischemia and Spreading Depolarization in Absence of Angiographic Vasospasm after Subarachnoid Hemorrhage

2011 ◽  
Vol 32 (2) ◽  
pp. 203-212 ◽  
Author(s):  
Johannes Woitzik ◽  
Jens P Dreier ◽  
Nils Hecht ◽  
Ingo Fiss ◽  
Nora Sandow ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Digital Subtraction Angiography ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Prolonged Release ◽  
Digital Subtraction ◽  
Angiographic Vasospasm ◽  
Electrode Strip ◽  
Subdural Electrode

It has been hypothesized that vasospasm is the prime mechanism of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Recently, it was found that clusters of spreading depolarizations (SDs) are associated with DCI. Surgical placement of nicardipine prolonged-release implants (NPRIs) was shown to strongly attenuate vasospasm. In the present study, we tested whether SDs and DCI are abolished when vasospasm is reduced or abolished by NPRIs. After aneurysm clipping, 10 NPRIs were placed next to the proximal intracranial vessels. The SDs were recorded using a subdural electrode strip. Proximal vasospasm was assessed by digital subtraction angiography (DSA). 534 SDs were recorded in 10 of 13 patients (77%). Digital subtraction angiography revealed no vasospasm in 8 of 13 patients (62%) and only mild or moderate vasospasm in the remaining. Five patients developed DCI associated with clusters of SD despite the absence of angiographic vasospasm in three of those patients. The number of SDs correlated significantly with the development of DCI. This may explain why reduction of angiographic vasospasm alone has not been sufficient to improve outcome in some clinical studies.

NEWTON-2 Cisternal (Nimodipine Microparticles to Enhance Recovery While Reducing Toxicity After Subarachnoid Hemorrhage): A Phase 2, Multicenter, Randomized, Open-Label Safety Study of Intracisternal EG-1962 in Aneurysmal Subarachnoid Hemorrhage

Neurosurgery ◽  
2020 ◽  
Vol 88 (1) ◽  
pp. E13-E26
Author(s):  
R Loch Macdonald ◽  
Daniel Hänggi ◽  
Nerissa U Ko ◽  
Tim E Darsaut ◽  
Andrew P Carlson ◽  
...  
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Internal Carotid ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Rescue Therapy ◽  
Delayed Cerebral Ischemia ◽  
Phase 2 ◽  
Open Label ◽  
Angiographic Vasospasm ◽  
Basal Cisterns

ABSTRACT BACKGROUND A sustained release microparticle formulation of nimodipine (EG-1962) was developed for treatment of patients with aneurysmal subarachnoid hemorrhage (aSAH). OBJECTIVE To assess safety, tolerability, and pharmacokinetics of intracisternal EG-1962 in an open-label, randomized, phase 2 study of up to 12 subjects. METHODS Subjects were World Federation of Neurological Surgeons grades 1 to 2, modified Fisher grades 2 to 4, and underwent aneurysm clipping within 48 h of aSAH. EG-1962, containing 600 mg nimodipine, was administered into the basal cisterns. Outcome on the extended Glasgow Outcome Scale (eGOS), pharmacokinetics, delayed cerebral ischemia and infarction, rescue therapy, and safety were evaluated. RESULTS The study was halted when a phase 3 study of intraventricular EG-1962 stopped because that study was unlikely to meet its primary endpoint. Six subjects were randomized (5 EG-1962 and 1 oral nimodipine). After 90-d follow-up, favorable outcome on the eGOS occurred in 1 of 5 EG-1962 and in the single oral nimodipine patient. Four EG-1962 and the oral nimodipine subject had angiographic vasospasm. One EG-1962 subject had delayed cerebral ischemia, and all subjects with angiographic vasospasm received rescue therapy except 1 EG-1962 patient. One subject treated with EG-1962 developed right internal carotid and middle cerebral artery narrowing 5 mo after placement of EG-1962, leading to occlusion and cerebral infarction. Pharmacokinetics showed similar plasma concentrations of nimodipine in both groups. CONCLUSION Angiographic vasospasm and unfavorable clinical outcome still occurred after placement of EG-1962. Internal carotid artery narrowing and occlusion after placement of EG-1962 in the basal cisterns has not been reported.

scholarly journals Hyperoxemia during the hyperacute phase of aneurysmal subarachnoid hemorrhage is associated with delayed cerebral ischemia and poor outcome: a retrospective observational study

2019 ◽  
pp. 1-8 ◽  
Author(s):  
Shinya Fukuda ◽  
Yasutaka Koga ◽  
Motoki Fujita ◽  
Eiichi Suehiro ◽  
Kotaro Kaneda ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Favorable Outcome ◽  
Regression Analyses ◽  
Poor Outcome ◽  
Poor Outcome Group ◽  
Outcome Group

OBJECTIVEThe harmful effects of hyperoxemia have been reported in critically ill patients with various disorders, including those with brain injuries. However, the effect of hyperoxemia on aneurysmal subarachnoid hemorrhage (aSAH) patients is unclear. In this study the authors aimed to determine whether hyperoxemia during the hyperacute or acute phase in patients with aSAH is associated with delayed cerebral ischemia (DCI) and poor neurological outcome.METHODSIn this single-center retrospective study, data from patients with aSAH treated between January 2011 and June 2017 were reviewed. The patients were classified into groups according to whether they experienced DCI (DCI group and non-DCI group) and whether they had a poor outcome at discharge (poor outcome group and favorable outcome group). The background characteristics and time-weighted average (TWA) PaO2 during the first 24 hours after arrival at the treatment facility (TWA24h-PaO2) and between the first 24 hours after arrival and day 6 (TWA6d-PaO2), the hyperacute and acute phases, respectively, were compared between the groups. Factors related to DCI and poor outcome were evaluated with logistic regression analyses.RESULTSOf 197 patients with aSAH, 42 patients experienced DCI and 82 patients had a poor outcome at discharge. TWA24h-PaO2 was significantly higher in the DCI group than in the non-DCI group (186 [141–213] vs 161 [138–192] mm Hg, p = 0.029) and in the poor outcome group than in the favorable outcome group (176 [154–205] vs 156 [136–188] mm Hg, p = 0.004). TWA6d-PaO2 did not differ significantly between the groups. Logistic regression analyses revealed that higher TWA24h-PaO2 was an independent risk factor for DCI (OR 1.09, 95% CI 1.01–1.17, p = 0.037) and poor outcome (OR 1.17, 95% CI 1.06–1.29, p = 0.002).CONCLUSIONSHyperoxemia during the first 24 hours was associated with DCI and a poor outcome in patients with aSAH. Excessive oxygen therapy might have an adverse effect in the hyperacute phase of aSAH.

scholarly journals Serum glucose as an important predictor of delayed cerebral ischemia in angiogram-negative subarachnoid hemorrhage

2021 ◽  
Author(s):  
Zeyu Zhang ◽  
Anke Zhang ◽  
Xiaoyu Wang ◽  
Yuanjian Fang ◽  
Yibo Liu ◽  
...  
Keyword(s):  
Logistic Regression ◽  
Regression Analysis ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Logistic Regression Analysis ◽  
Delayed Cerebral Ischemia ◽  
Multivariate Logistic Regression Analysis ◽  
Serum Glucose ◽  
World Federation ◽  
Symptomatic Vasospasm

Abstract Background Despite benign overall course, angiogram-negative subarachnoid hemorrhage (AN-SAH) still companies with risk of delayed cerebral ischemia (DCI). Serum glucose was previously found to be related to DCI occurrence in aneurysmal subarachnoid hemorrhage (aSAH), but this has not been confirmed in AN-SAH. The aim of this study was to clarify the significance of serum glucose in DCI prediction in AN-SAH patients. Methods We included patients with AN-SAH admitted to our hospital between January 2013 and December 2018. According to different bleeding patterns, patients were divided into perimesencephalic AN-SAH (PAN-SAH) and non-perimesencephalic AN-SAH (NPAH-SAH) patients. DCI was defined as symptomatic vasospasm or/and delayed cerebral infarction. A statistical analysis of the clinical, radiological, and laboratory risk factors of DCI was conducted. Logistic regression analysis was performed to identify the independent predictors of DCI. Results A total of 244 AN-SAH patients (mean age 55.7 years, 55.7% men) were included with 164 (67.2%) PAN-SAH patients and 80 (32.8%) NPAN-SAH patients. There were significant correlations between high DCI incidence and high serum glucose levels in the first five days after admission in both PAN-SAH patients and NPAN-SAH patients (p < 0.05). High admission serum glucose was significantly related to higher World Federation of Neurosurgeons Scale (WFNS) (p < 0.05). Multivariate logistic regression analysis showed that admission serum glucose (p = 0.001, OR 1.705, 95% CI 1.232–2.360) and WFNS (p = 0.008, OR 2.889, 95% CI 1.322–6.311) were both significant and independent predictors for DCI occurrence in PAN-SAH patients. Admission serum glucose (p = 0.016, OR 2.307, 95% CI 1.167–4.562), standard deviation (SD) of the serum glucose in the first three days after admission (p = 0.049, OR 5.684, 95% CI 1.006–32.114) and modified Fisher scale (mFS) (p = 0.033, OR 1.859, 95% CI 1.051–3.288) were significant and independent predictors for DCI occurrence in NPAN-SAH patients. Conclusions Serum glucose is an early biomarker to predict DCI risk in both PAN-SAH and NPAN-SAH patients, which has an important value in guiding intensive care in AN-SAH patients.

Machine learning improves prediction of delayed cerebral ischemia in patients with subarachnoid hemorrhage

2018 ◽  
Vol 11 (5) ◽  
pp. 497-502 ◽  
Author(s):  
Lucas Alexandre Ramos ◽  
Wessel E van der Steen ◽  
Renan Sales Barros ◽  
Charles B L M Majoie ◽  
Rene van den Berg ◽  
...  
Keyword(s):  
Machine Learning ◽  
Logistic Regression ◽  
Subarachnoid Hemorrhage ◽  
Cerebral Ischemia ◽  
Regression Models ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Delayed Cerebral Ischemia ◽  
Image Data ◽  
Image Features ◽  
Logistic Regression Models

Background and purposeDelayed cerebral ischemia (DCI) is a severe complication in patients with aneurysmal subarachnoid hemorrhage. Several associated predictors have been previously identified. However, their predictive value is generally low. We hypothesize that Machine Learning (ML) algorithms for the prediction of DCI using a combination of clinical and image data lead to higher predictive accuracy than previously applied logistic regressions.Materials and methodsClinical and baseline CT image data from 317 patients with aneurysmal subarachnoid hemorrhage were included. Three types of analysis were performed to predict DCI. First, the prognostic value of known predictors was assessed with logistic regression models. Second, ML models were created using all clinical variables. Third, image features were extracted from the CT images using an auto-encoder and combined with clinical data to create ML models. Accuracy was evaluated based on the area under the curve (AUC), sensitivity and specificity with 95% CI.ResultsThe best AUC of the logistic regression models for known predictors was 0.63 (95% CI 0.62 to 0.63). For the ML algorithms with clinical data there was a small but statistically significant improvement in the AUC to 0.68 (95% CI 0.65 to 0.69). Notably, aneurysm width and height were included in many of the ML models. The AUC was highest for ML models that also included image features: 0.74 (95% CI 0.72 to 0.75).ConclusionML algorithms significantly improve the prediction of DCI in patients with aneurysmal subarachnoid hemorrhage, particularly when image features are also included. Our experiments suggest that aneurysm characteristics are also associated with the development of DCI.

Sign in / Sign up

Export Citation Format

Share Document