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Outcomes of Anesthesia Selection in Endovascular Treatment of Acute Ischemic Stroke

Peng, Yuming, MD, PhD*; Wu, Youxuan, MD*; Huo, Xiaochuan, MD, PhD; Wu, Peng, PhD; Zhou, Yang, MD*; Li, Jiaxin, MD*; Liang, Fa, MD*; Liu, Xiaoyuan, MD, PhD*; Pan, Yuesong, PhD; Miao, Zhongrong, MD, PhD; Han, Ruquan, MD, PhD* on behalf of Endovascular Therapy for Acute Ischemic Stroke Trial (EAST) group

Journal of Neurosurgical Anesthesiology: January 2019 - Volume 31 - Issue 1 - p 43–49
doi: 10.1097/ANA.0000000000000500
Clinical Investigations

Background: The association between anesthesia type and outcomes in patients with acute ischemic stroke undergoing endovascular treatment (EVT) remains a subject of ongoing debate.

Methods: 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.

Results: 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, P>0.05) 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.

Conclusions: 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.

Departments of *Anesthesiology

Interventional Neurology

Neurology, Tiantan Clinical Trial and Research Center for Stroke, Beijing Tiantan Hospital, Capital Medical University, Beijing, PR China

Z.M. and R.H. contributed equally.

Y.P., Z.M., and R.H.: helped with the study design and manuscript preparation. Y.W., J.L., and F.L.: helped with the data collection and manuscript preparation. X.H. helped with the patient recruitment. X.L. and Y.Z.: helped with the data collection. P.W. and Y.P.: helped with the data analyses.

Clinical Trial Registration: (NCT02350283).

The trial was funded by the ‘Youth Program’ (QML20150508) and Hospitals Clinical Medicine Development of Special Funding Support (ZYLX201708) from the Beijing Municipal Administration of Hospitals and programs from National Science and Technology Major Project of China (2011BAI08B02, 2015BAI12B04, and 2015BAI12B02).

The authors have no conflicts of interest to disclose.

Address correspondence to: Ruquan Han, MD, PhD, Department of Anesthesiology, Beijing Tiantan Hospital, Capital Medical University, No. 6, Tiantan Xili, Dongcheng District, Beijing 100050, PR China (e-mail:

Received November 28, 2017

Accepted March 12, 2018

Acute stroke is one of the leading causes of death and long-term disability,1 particularly in China. Timely reperfusion of the occluded large vessel through endovascular treatment (EVT) is effective for decreasing neuronal damage and improve outcomes.2,3 However, there is no definite evidence on the selection of anesthesia for acute ischemic stroke (AIS) patients undergoing EVT.

General anesthesia (GA) and local anesthesia, with or without conscious sedation (CS), are commonly used during EVT.4,5 However, the association between anesthesia selection and independent outcomes is controversial. Observational studies have indicated that acute stroke patients receiving GA for EVT had worse outcomes than those who underwent local anesthesia, with or without CS,6–12 and this finding was confounded by several factors.13 The conclusion has been debated in completed randomized controlled trials (RCTs) in which anesthesia choice was randomized.14–16 In addition, there is still no evidence from China on the association between anesthesia selection and clinical outcomes, in which large artery atherosclerosis was the primary etiological diagnosis.

The aim of the study was to prospectively investigate the anesthesia strategy and the associated independent outcomes, which were derived from the intervention arm of the Endovascular Therapy for Acute Ischemic Stroke Trial (EAST). The specific hypothesis was that local anesthesia, with or without CS, improved 90-day independence in AIS patients compared with GA.

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The EAST trial was a multicentre, prospective, nonrandomized controlled study conducted in 17 stroke centers across China, and consecutive patients with AIS were recruited from January 2015 to August 2015. A central medical ethics committee (Medical Ethics Committee, Beijing Tiantan Hospital, Capital Medical University) approved the study protocol. The EAST trial was registered on (number: NCT02350283). All written informed consent before study enrolment was provided by legal representatives. The protocol of the EAST trial has been previously published.17 Patients in the intervention group were treated with mechanical recanalization using Solitaire plus standard medical therapy. Patients in the control group received standard medical therapy alone.

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Eligible patients were diagnosed with AIS due to large vessel occlusion indicated for EVT within 12 hours after symptom onset and met the inclusion criteria: (1) age 18 years and older; (2) a clinical diagnosis of ischemic stroke, with symptoms present for at least 30 minutes and without significant improvement before treatment; (3) a prestroke modified Rankin Scale (mRS) score ≤1; (4) National Institute of Health Stroke Scale (NIHSS) score ≥8 and <30; (5) occlusion at ≥1 of the following sites (as determined through single-phase, multiphase or dynamic computed tomography (CT) angiography or digital subtraction angiography): carotid T/L, M1-middle cerebral artery (MCA), or M2-MCA equivalent affecting at least 50% of the MCA territory; and (6) provided written informed consent. Patients with an Alberta Stroke Program Early CT Score (ASPECTS) from 0 to 6 in the area of symptomatic intracranial occlusion or a DWI lesion volume >50 mL were excluded from the study. Patients in the control arm receiving standard medical therapy alone were excluded from the study.

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All patients in the intervention arm underwent complete 4-vessel cerebral angiography performed by fully trained interventional neuroradiologists. When the diagnostic angiography revealed arterial occlusion, thrombectomy with a Solitaire stent was performed as the primary treatment. At the end of treatment, recanalization was classified according to the modified thrombolysis in cerebral infarction (mTICI) perfusion grade.18

GA was defined as induction and maintenance with sedation drugs, analgesic agents and muscle relaxants, with controlled ventilation under tracheal intubation or laryngeal mask, from the time of groin puncture to the end of the procedure. If a patient underwent tracheal intubation before entering the procedural room, the patient was excluded from the analysis. CS was defined as local anesthesia and spontaneous breathing, with or without administration of sedatives throughout the procedure. Conversion from CS to GA during the procedure was another exclusion criterion. The selection of anesthesia was not predefined in the protocol.

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The primary outcome was functional independence as defined by a mRS of 0 to 2 and assessed by a neurologist who was blinded to the treatment details at 90 days after the EVT during an outpatient visit. If a patient was unable to come to the clinic, the mRS score was assessed through a telephone interview. The mRS was a 7-point scale ranging from 0 (no symptoms) to 6 (deceased).

The secondary outcomes were arterial reperfusion of the occluded target vessel measured by mTICI (2b-3) at the end of treatment by 2 experienced neurointerventionalists who were blinded to the clinical data and outcomes. The periprocedural hemodynamic parameters were recorded including systolic blood pressure (SBP), diastolic blood pressure, and mean arterial pressure (MAP). The neurological assessment was measured by using the NIHSS score (range from 0 to 42, with higher scores indicating more severe neurological deficits) at 2 hours, 24 hours, and 7 days after the procedure. Quality of life was evaluated by the European life quality (EQ-5D) score and the Barthel Index (BI) score at 90 days. The rates of device-related and procedure-related complications were evaluated and recorded at discharge. Death due to any cause at 90 days was measured. Symptomatic intracerebral hemorrhage was detected by CT or magnetic resonance imaging at 24±3 hours postprocedure. An economic (cost-effectiveness) analysis, including the total length of intensive care unit and hospital stays and the inpatient cost in US dollars, was performed at discharge.

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Statistical Analysis

The EAST trial was an exploratory study that aimed to observe the safety and the efficacy of Solitaire thrombectomy in patients with AIS. The sample size of the AIS patients undergoing EVT was prospectively calculated as 150. Descriptive statistics were reported as the means with SDs for normally distributed data, medians with interquartile ranges for skewed continuous data, and counts (percentages) for categorical data. Categorical variables were analyzed with the χ2 test, and continuous variables were analyzed using the Student t test or Wilcoxon test between patients who received GA and CS.

Binary and continual outcomes were analyzed through logistic and linear regression, and the results were reported as adjusted and unadjusted odds ratios (ORs) and β coefficients, with 95% confidence intervals (CIs), respectively. The primary outcome was adjusted for potential imbalances in known prognostic variables, as reported by previous literature and our differential comparison results, including age, sex, body mass index, smoke history, NIHSS on admission, treatment with r-tPA, onset-to-recanalization time and mTICI (2b-3). Statistical significance was declared with a type I error of 0.05. SPSS 17.0 (SPSS Inc., Chicago, IL) was used for the statistical analyses.

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Patient Characteristics

Among the 149 patients enrolled in the trial, 44 (29.5%) underwent GA, and 105 (70.5%) received CS (Fig. 1).



The demographics, past medical history, baseline NIHSS, results of laboratory studies, and occlusion site did not differ between the patients receiving different types of anesthesia (P>0.05, see Table 1) with the exception of sex and puncture-to-recanalization time. The male sex proportion (54.3% vs. 79.6%, P=0.004), and puncture-to-recanalization time (50, 35 to 85 vs. 73, 46 to 109; P=0.028) differed, but the onset-to-recanalization time and recanalization rate, evaluated as mTICI 2b-3, did not differ between the patients who received CS and those who received GA.



No patients were lost to follow-up. The primary outcome, independence (mRS score 0 to 2) at 3 months, did not differ between the patients who received CS and those who received GA either before (OR, 0.72; 95% CI, 0.35-1.48) or after the adjustments (OR, 0.73; 95% CI, 0.32-1.68, Table 2). Moreover, we did not observe a shift in the distribution of the mRS score in favor of the CS group compared with the GA group (Fig. 2).





After EVT, the NIHSS at 24 hours for patients receiving CS was significantly lower than that for the patients who received GA (8.3-15 vs. 11.9-15.5, P=0.038); however, the NIHSS at 2 hours and 7 days did not differ (Table 2). The other outcomes, such as the BI score (75 to 100), EQ-5D, and mortality and morbidity rates (symptomatic intracerebral hemorrhage and complications with instruments and operations), did not differ between the patients undergoing CS and GA. The length of intensive care unit and hospital stay, and the total inpatient cost in US dollars were similar between the patients receiving GA and CS.

Among the patients who received local anesthesia at 14 centers, 7 (6.7%) patients did not receive any sedative, and 98 (93.3%) patients received sedatives. In contrast, only 23 patients who received CS at 2 centers were administered sedatives by the anesthesiologists, and the other 75 were administered by the interventionists. Dexmedetomidine was the most frequently used sedative (48, 45.7%). Among the patients who received GA at 12 centers, all were administered anesthesia by anesthesiologists. Sufentanil (37, 84.1%), with etomidate (22, 50%) or propofol (19, 43.2%), was often used to induce GA, and propofol, with (15, 34.1%) or without (28, 63.6%) volatile agents, was used for maintenance (Table 3).



SBP and MAP were found to be significantly lower in patients who received GA 30 minutes after induction compared with patients who received CS at the respective time points (Fig. 3). However, the number of patients who received vasoactive drugs was not significantly different between the 2 anesthesia types (Table 4). The fluid input for patients receiving GA included crystalloid (618±248 mL) and colloid solution (685±300 mL), whereas only crystalloid (650±124 mL) was administered to patients who received CS, and the difference in the input amount was significant (P<0.05).





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This anesthesia-related analysis of a multicentre, prospective study assessed the association between anesthesia selection and outcomes from the EVT for AIS. The primary outcome of independence (mRS 0-2) at 3 months, as well as the mortality and morbidity rates, did not differ between the patients who received GA and those who received CS; however, the hemodynamic parameters and the fluid input were significantly different between the patients receiving the 2 types of anesthesia.

Previous observational studies have found better 90-day independent outcomes in patients who received CS6; however, the imbalance in age,19 ischemic severity,7,8,10,11,20 and ischemic site21 led to concern with regard to the selection bias and a cautious interpretation of the conclusion. Moreover, the association was also confounded by the intraprocedural parameters, such as the decrease in MAP >40%,22 the minimal diastolic blood pressure and the maximal SBP variability.21 Therefore, the preprocedure ischemia (site and severity) and the intraprocedure hemodynamic fluctuation were often regarded as confounding factors between anesthesia selection and independence after EVT. The sensitivity analysis from the recent metaanalysis23 indicated that the pooled incidence of independence (mRS score 0 to 2) from the RCTs favored GA; however, patients receiving GA had significantly higher morbidity and mortality rates compared with patients who received CS. Therefore, the evidence for selection of anesthesia for AIS patients undergoing EVT still requires results from a diverse population. Our results were from a nonrandomized study. However, the baseline NIHSS, the ischemic site, and the other preprocedure parameters were all comparable between the patients receiving the 2 types of anesthesia, and the primary outcome was also in accordance with the AnStroke trial,15 which studied the same subjects with anterior circulation ischemia. However, the other 2 recently completed trials, both SIESTA14 and GOLIATH,16 favored GA from the point of better 90-day independent outcome (mRS score 0 to 2).

The time from onset-to-recanalization is critical for the independent outcome in AIS patients after EVT, which may be affected by the etiological cause of ischemia. Good clinical outcomes at 90 days (mRS 0-2) was greatest with time from symptom onset to arterial puncture of under 2 hours and became nonsignificant after 7.3 hours,24 and was also closely related with the time to reperfusion.25 The TOAST classification of large artery atherosclerosis was found in 69 patients (46.3%) in our trial, and the onset-to-puncture time in our study was ~238 and 254 minutes in patients who received GA and CS, respectively, both of which were in the suggested effective time window. In addition, the onset-to-recanalization time in our trial (304 min in CS vs. 311 min in GA) was slightly longer than that in the AnStroke trial (250 min in CS vs. 254 min in GA),15 comparable with that reported in the MR CLEAN trial (349 min in CS vs. 334 min in GA)12 and shorter than those in some previous observational studies.9,26 In the current trial, the recanalization time would not influence the association between anesthesia selection and outcomes in AIS patients undergoing EVT.

The proportion of GA administered to patients undergoing EVT was higher in some observational studies10,20 than that in our study; however, in some recent trials,12,19,27 this proportion was lower than those found in the above-mentioned observational studies. It often takes more time to prepare GA induction and tracheal intubation than to prepare CS for patients, and needs more cooperation from anesthesiologists. Therefore, CS was the first choice of the interventional neurologists for EVT. In the EAST trial, the mean difference between GA and CS in door-to-puncture time (11 min) and onset-to-recanalization time (7 min) were acceptable. This small time difference might be explained by the fact that a special team of anesthesiologists was on duty at the intervention-treatment room to conduct all GA, but the agents for CS were administered by the anesthesiologists in only 23 cases (23.5%) in 2 centers (13.3%) and by the interventionists for the other cases. This time difference was not the confounding factor between anesthesia selection and independence for the patients who received EVT.

In the EAST trial, dexmedetomidine was the most frequently used agent (45.7%) during sedation; however, all administrations were performed by interventionists. In addition, no patients received analgesic or colloid during CS. Hence, a series of problems for AIS patients under sedation could occur, including substantial movement, respiratory depression and high conversion rate from sedation to GA. Even in the SIESTA14 trial, in which the anesthesia selection was randomized, a high rate of substantial movement, diverse drug choices and a high rate of conversion from CS to GA were detected. However, the number of movement and respiratory parameters were not recorded in the EAST trial. In addition, the proportions of induction with sufentanil and etomidate and maintenance with total intravenous anesthesia increased in this study compared with the study conducted by Jagani et al,21 in which fentanyl and propofol were primarily used. SBP and MAP were significantly decreased within 30 minutes after induction; however, the number of patients who received vasoactive drugs, particularly a vasoconstrictor, did not differ between the patients under the 2 anesthesia types, and a >40% decrease in MAP from the preprocedure value was not found in patients receiving GA.

This study has several limitations. First, the data were from a nonrandomized trial, and the anesthesia choice was decided by the interventional neurologists. However, the baseline characteristics of ischemia and demographics were well balanced. Second, the sample size was not calculated but predefined in the EAST trial and might be not sufficient to test the difference in 90-day mRS between the different anesthesia types. However, we calculated the power for testing the primary outcome divided by the anesthesia type as >85%. Third, some anesthesia-specific information was not collected in detail, including the ventilator parameters, end-expiratory carbon dioxide and real-time hemodynamic parameters, which might be potential risk factors for the independent outcome. However, the EAST study was an exploratory trial and had provided a foundation for further research in such populations, such as the ongoing CANVAS trial,5 a multicentre, parallel-group RCT observing the effect of anesthesia selection on independent outcome in patients with acute anterior circulation stroke undergoing EVT.

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Among patients with AIS in the anterior circulation undergoing EVT, CS compared with GA did not result in more improvements in the independent status at 3 months after the procedure. RCTs are still needed to provide more perioperative evidence of the hemodynamics and respiration effects of anesthesia choice on outcomes of patients with AIS during EVT.

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We gratefully acknowledge the enrolled centers and investigators for their outstanding work. The following centers and investigators were involved: Ya Peng, MD, Department of Neurosurgery, Changzhou No. 1 People’s Hospital, Changzhou, China; Yibin Cao, MD, Department of Neurology, Tangshan Gongren Hospital, Tangshan, China; Shengli Chen, MD, Department of Neurology, Chongqing Sanxia Central Hospital, Chongqing, China; Meng Zhang, MD, Department of Neurology, Daping Hospital, Chongqing, China; Changchun Jiang, MD, Department of Neurology, Baotou Central Hospital, Baotou, China; Xiaoxiang Peng, MD, Department of Neurology, Hubei Zhongshan Hospital, Wuhan, China; Cunfeng Song, MD, Department of Neurology, Liaocheng 3rd People’s Hospital, Liaocheng, China; Liping Wei, MD, Department of Neurology, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang, China; Qiyi Zhu, MD, Department of Neurology, People’s Hospital of Linyi City, China; Zaiyu Guo, MD, Department of Neurology, Tianjin Teda Hospital, Tianjin, China; Li Liu, MD, Department of Neurology, Chifeng Municipal Hospital, Chifeng, China; Hang Lin, MD, Department of Neurology, Fuzhou PLA General Hospital, Fuzhou, China; Hua Yang, MD, Department of Neurology, Affiliated Hospital of Guiyang Medical College, Guiyang, China; Wei Wu, MD, Department of Neurology, QiLu Hospital of ShanDong University, Jinan, China; Hui Liang, MD, Department of Neurology, Yantai Hill Hospital, Yantai, China; Anding Xu, MD, Department of Neurology, The First Affiliated Hospital of Jinan University, China; and Kangning Chen, MD, Department of Neurology, Xinan Hospital, China.

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acute ischemic stroke; anesthesia; large artery occlusion; outcome

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