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OBJECTIVE Stellate ganglion block (SGB) is a commonly used sympathetic nerve block technique that may have benefits for patients with aneurysmal subarachnoid hemorrhage (aSAH) in the early stage. Cerebral vasospasm (CVS), one of the most common complications of aSAH, is accompanied by an abnormal increase in cerebral blood flow velocity (CBFV) and neurological dysfunction. In this pilot study the authors sought to determine the feasibility of early SGB for CVS in aSAH patients by observing the incidence of symptomatic CVS. METHODS Prior to receiving surgical treatment, patients with aSAH were randomly assigned to the SGB group or the non-SGB group. The primary outcome was the incidence of symptomatic CVS within 14 ± 2 days after the onset of aSAH. As a higher CBFV is often associated with CVS and a poor prognosis, the mean CBFV of the middle cerebral artery was observed immediately after surgery and on postoperative days 1, 2, 3, 5, and 7. Other secondary outcomes included transcranial Doppler (TCD)/CTA-type CVS, delayed cerebral ischemia during hospitalization, new cerebral infarction within 3 months, adverse events (AEs), and clinical prognosis. RESULTS Symptomatic CVS occurred in 40% of patients in the non-SGB group and in 20% in the SGB group (RR 0.50, 95% CI 0.22–1.16). Continuous TCD sonography revealed that the postoperative mean CBFV was lower in the SGB group than in the non-SGB group (F = 3.608, p = 0.02). In addition, the percentages of patients with CVS evaluated by TCD (TCD-CVS) and total new infarctions within 3 months were also significantly lower than those in patients with CVS (TCD-CVS 36.7% vs 70%, RR 0.52, 95% CI 0.31–0.89, and total new infarctions 26.7% vs 53.3%, RR 0.50, 95% CI 0.25–0.99). In terms of AEs and mortality, there were no significant differences between the two groups. CONCLUSIONS This pilot study demonstrated for the first time, to the authors’ knowledge, that early SGB is feasible and has the potential to reduce the risk of CVS and improve the prognosis of aSAH. This method may be a new treatment for patients with aSAH that may have more advantages than traditional therapeutic drugs and is worth further study. Clinical trial registration no.: NCT04691271 (ClinicalTrials.gov)

No definitive conclusion can be made on the best choice of anesthesia for people with acute posterior circulation stroke during endovascular treatment. Only a few observational studies have focused on this topic in recent years, and they have differing conclusions.To examine whether conscious sedation (CS) is a feasible alternative to general anesthesia (GA) during endovascular treatment in patients with acute posterior circulation stroke.A randomized parallel-group exploratory trial with blinded end point evaluation (Choice of Anesthesia for Endovascular Treatment of Acute Ischemic Stroke [CANVAS II]) enrolled adult patients from March 2018 to June 2021 at 2 comprehensive care hospitals in China. Patients with acute posterior circulation stroke were enrolled, randomized, and monitored for 3 months. Of 210 patients admitted with acute ischemic posterior circulation stroke, 93 were recruited and 87 were included in the intention-to-treat (ITT) analysis after exclusions, 43 were assigned to GA and 44 to CS. All analyses were unadjusted or adjusted with the ITT principle.Participants were randomly assigned to CS or GA in a 1:1 ratio.The primary end point was functional independence at 90 days evaluated with the modified Rankin Scale (mRS).A total of 87 participants were included in the ITT study (mean [SD] age, 62 [12] years; 16 [18.4%] female and 71 [81.6%] male). Of these, 43 were in the GA group and 44 in the CS group. The overall baseline median (IQR) National Institute of Health Stroke Scale (NIHSS) score was 15 (12-17). In the CS group, 13 people (29.5%) were ultimately transferred to GA. The CS group had a higher incidence of functional independence; however, no significant difference was found between the 2 groups (48.8% vs 54.5%; risk ratio, 0.89; 95% CI, 0.58-1.38; adjusted odds ratio [OR], 0.91; 95% CI, 0.37-2.22). However, GA performed better in successful reperfusion (mTICI 2b-3) under ITT analysis (95.3% vs 77.3%; adjusted OR, 5.86; 95% CI, 1.16-29.53).The findings in this study suggest that CS was not better than GA for the primary outcome of functional recovery and was perhaps worse for the secondary outcome of successful reperfusion.ClinicalTrials.gov Identifier: NCT03317535.

Aim: This study has been designed to assess the bioequivalence of the newly developed delayed-release oral tablets (test) 30 mg nifedipine compared to its marketed counterpart (30 mg; reference) in healthy adult Chinese volunteers. Methods: We conducted randomized, open-label, four-period, crossover trials, including a fasting trial and a fed trial. The subjects were administered the test or reference products in a 1:1 ratio at random throughout each period with 7 days washout period. Then, in the next session, they got the alternate products. Liquid chromatography-tandem mass spectrometry and WinNonlin software were used to evaluate the bioequivalence of nifedipine peak blood concentration (Cmax) and area under the concentration-time curve (AUC). Result: A total of 46 subjects participated in the fasting trial and 48 subjects in the postprandial trial. In both cases, the 90% CI of the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were in the equivalence range (80-125%). When nifedipine was given concomitantly with a high-fat meal, tmax was approximately twofold earlier, absorption was approximately 4.8% less, and Cmax changed little compared to fasting conditions. In addition, no serious adverse events were observed in the subjects. Conclusion: This study confirms the bioequivalence of the test and reference formulations of nifedipine extended-release tablets under fasting and postprandial conditions. Food giving leads to a much earlier Tmax, which is different from the results of other studies. The effect of food effect on the pharmacokinetics of nifedipine needs to be further explored.

There is continued controversy regarding the optimal anesthetic technique for endovascular therapy in patients with acute posterior circulation ischemic stroke. To compare the clinical outcomes general anesthesia (GA) and non-GA, we performed a systematic review and meta-analysis of randomized controlled trials and observational studies focused on the anesthetic management for endovascular therapy in patients with acute posterior circulation stroke, without language restriction. In addition, we compared clinical outcomes among the studies with different non-GA types (conscious sedation or local anesthesia). Outcome variables were functional independence, excellent outcomes, favorable outcomes, mortality, successful recanalization, hemodynamic instability, intracerebral hemorrhage, and respiratory or vascular complications. Eight studies including 1777 patients were identified. Although GA was associated with a lower odds of functional independence at 90 days (odds ratio [OR]: 0.55; 95% confidence interval [CI] 0.38 to 0.81; P=0.009), substantial heterogeneity was noted (I2=65%). Subgroup analysis showed that GA was associated with higher odds of mortality than conscious sedation (OR: 1.83; 95% CI, 1.30 to 2.57; I2=0%), but there was no difference between GA and local anesthesia (I2=0%). Interestingly, subgroup analysis did not identify a relationship between functional independence and GA compared with local anesthesia (OR: 0.90; 95% CI, 0.64 to 1.25; P=0.919; I2=0%). This meta-analysis demonstrates that GA is associated with worse outcomes in patients with acute posterior circulation stroke undergoing endovascular therapy based on current studies.

Introduction Stellate ganglion block has been reported to expand cerebral vessels and alleviate vasospasm after aneurysmal subarachnoid hemorrhage. However, the causal relationship between early stellate ganglion block and cerebral vasospasm prevention has not yet been established. Methods/design This is a single-center, prospective, randomized, controlled, blinded-endpoint assessment trial to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment for cerebral vasospasm and delayed cerebral ischemia. A total of 228 patients will be randomized within 48 h of aneurysmal subarachnoid hemorrhage onset in a 1:1 ratio to two groups with an additional e-SGB or only a camouflaging action before craniotomy aneurysm clipping. The primary efficacy outcome is the incidence of symptomatic vasospasm within 14 days after aSAH. Further safety and efficacy parameters include the incidence of radiographic vasospasm, new cerebral infarction, postoperative delirium, and complications up to 90 days, postoperative cerebral hemodynamics, mini-mental state examination, the modified Rankin scale and all-cause mortality up to 90 days.Discussion This is the first randomized controlled trial to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment to reduce cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. If the result is positive, it may provide a new direction for the prevention and treatment of cerebral vasospasm and delayed cerebral ischemia.Trial registration ClinicalTrials.gov NCT04691271

Author(s): Sun, Jian; Liang, Fa; Wu, Youxuan; Zhao, Yan; Miao, Zhongrong; Zhang, Li; Gelb, Adrian W; Chan, Matthew TV; Peng, Yuming; Han, Ruquan; CANVAS Pilot Trial Investigators | Abstract: BackgroundThe effect of choice of anesthesia on clinical outcome for endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) remains unclear.MethodsWe conducted a pilot trial of 43 patients with acute anterior circulation ischemic stroke having EVT. Patients were randomly allocated to receive general anesthesia or conscious sedation. We documented the rate of recruitment and rate of conversion from conscious sedation to general anesthesia. In addition, we recorded the change in National Institute of Health stroke scale (NIHSS) on day 7, the rate of successful reperfusion and measured neurological function by certified researchers using modified Rankin Score (mRS 0 to 2) at 90 days.ResultsThe recruitment rate was 31.4% and majority of patients were excluded because of delay in hospital presentation and posterior circulation stroke. The rate of conversion from conscious sedation to general anesthesia was 18.2%. This was primarily related to excessive sedation and uncontrolled movement. Change in NIHSS score, rate of successful reperfusion and functional recovery were similar between groups.ConclusionsIt was feasible to randomize AIS patients receiving either general anesthesia or conscious sedation for EVT.

Consciousness is supported by rich neuronal dynamics to orchestrate behaviors and conscious processing can be disrupted by general anesthetics. Previous studies suggested that dynamic reconfiguration of large-scale functional network is critical for learning and higher-order cognitive function. During altered states of consciousness, how brain functional networks are dynamically changed and reconfigured at the whole-brain level is still unclear. To fill this gap, using multilayer network approach and functional magnetic resonance imaging (fMRI) data of 21 healthy subjects, we investigated the dynamic network reconfiguration in three different states of consciousness: wakefulness, dexmedetomidine-induced sedation, and recovery. Applying time-varying community detection algorithm, we constructed multilayer modularity networks to track and quantify dynamic interactions among brain areas that span time and space. We compared four high-level network features (i.e., switching, promiscuity, integration, and recruitment) derived from multilayer modularity across the three conditions. We found that sedation state is primarily characterized by increased switching rates as well as decreased integration, representing a whole-brain pattern with higher modular dynamics and more fragmented communication; such alteration can be mostly reversed after the recovery of consciousness. Thus, our work can provide additional insights to understand the modular network reconfiguration across different states of consciousness and may provide some clinical implications for disorders of consciousness.

The effect of choice of anesthesia on clinical outcome for endovascular treatment (EVT) in patients with acute ischemic stroke (AIS) remains unclear.We conducted a pilot trial of 43 patients with acute anterior circulation ischemic stroke having EVT. Patients were randomly allocated to receive general anesthesia or conscious sedation. We documented the rate of recruitment and rate of conversion from conscious sedation to general anesthesia. In addition, we recorded the change in National Institute of Health stroke scale (NIHSS) on day 7, the rate of successful reperfusion and measured neurological function by certified researchers using modified Rankin Score (mRS 0 to 2) at 90 days.The recruitment rate was 31.4% and majority of patients were excluded because of delay in hospital presentation and posterior circulation stroke. The rate of conversion from conscious sedation to general anesthesia was 18.2%. This was primarily related to excessive sedation and uncontrolled movement. Change in NIHSS score, rate of successful reperfusion and functional recovery were similar between groups.It was feasible to randomize AIS patients receiving either general anesthesia or conscious sedation for EVT.

The association between anesthesia type and outcomes in patients with acute ischemic stroke undergoing endovascular treatment (EVT) remains a subject of ongoing debate.This prospective nonrandomized controlled trial included 149 consecutive patients with acute anterior circulation stroke who underwent EVT. The primary outcome was functional independence assessed by the modified Rankin Scale (mRS) after 3 months.A total of 105 (70.5%) and 44 (29.5%) patients undergoing EVT who received conscious sedation (CS) and general anesthesia (GA), respectively. The patients who received GA had similar demographics and basic National Institute of Health Stroke Scale scores (17 vs. 16, P0.05) as the patients who received CS. The recanalization time (304 vs. 311 min, P=0.940) and the recanalization rate (86.4% vs. 84.1%, P=0.170) did not differ between the patients receiving the different types of anesthesia. The National Institute of Health Stroke Scale at 24 hours was lower in the patients who received CS than in those who received GA (β=-2.26, 95% confidence interval, -5.30 to 0.79). The independence (modified Rankin Scale score 0 to 2) at 3 months was equal between patients who received GA and those who received CS (odds ratio=0.73, 95% confidence interval, 0.32-1.68). The mortality and the morbidity rates did not differ.The data indicated that the selection of GA or CS during EVT had no impact on the independent outcomes of patients with anterior circulation occlusion.

Our previous studies demonstrated that tanshinone IIA (tan IIA) has significant protective effects against the neurotoxicity induced by β-amyloid protein (Aβ) in cultured cortical neurons and PC12 cells. This study was designed to investigate the protective effects of tan IIA against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease (AD). STZ was injected twice intracerebroventrically (3mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with tan IIA (20, 40, and 80mg/kg, i.g.) starting from the first dose of STZ for 28 days showed a dose dependent improvement in STZ induced memory deficits as assessed by Morris water maze (MWM) test. Nissl staining results confirmed the protective effects of tan IIA on cerebral cortical and hippocampal neurons damage induced by STZ. In addition, tan IIA markedly reduced STZ induced elevation in acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and significantly inhibited STZ induced reduction in superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities in the parietal cortex and hippocampus. Moreover, tan IIA attenuated p38 mitogen activated protein kinase (MAPK) phosphorylation in the parietal cortex and hippocampus. These findings demonstrate that tan IIA prevents STZ induced memory deficits may be attributed to ameliorating neuronal damage, restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. Based on our previous studies, the present study provides further support for the potential use of tan IIA in the treatment of AD.