IMPORTANCE Optimal management of sedation and airway during thrombectomy for acute ischemic stroke is controversial due to lack of evidence from randomized trials. OBJECTIVE To assess whether conscious sedation is superior to general anesthesia for early neurological improvement among patients receiving stroke thrombectomy. DESIGN, SETTING, AND PARTICIPANTS SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment), a single-center, randomized, parallel-group, open-label treatment trial with blinded outcome evaluation conducted at Heidelberg University Hospital in Germany (April 2014-February 2016) included 150 patients with acute ischemic stroke in the anterior circulation, higher National Institutes of Health Stroke Scale (NIHSS) score (>10), and isolated/combined occlusion at any level of the internal carotid or middle cerebral artery.INTERVENTION Patients were randomly assigned to an intubated general anesthesia group (n = 73) or a nonintubated conscious sedation group (n = 77) during stroke thrombectomy.MAIN OUTCOMES AND MEASURES Primary outcome was early neurological improvement on the NIHSS after 24 hours (0-42 [none to most severe neurological deficits; a 4-point difference considered clinically relevant]). Secondary outcomes were functional outcome by modified Rankin Scale (mRS) after 3 months (0-6 [symptom free to dead]), mortality, and peri-interventional parameters of feasibility and safety. RESULTS Among 150 patients (60 women [40%]; mean age, 71.5 years; median NIHSS score, 17), primary outcome was not significantly different between the general anesthesia group (mean NIHSS score, 16.8 at admission vs 13.6 after 24 hours; difference, −3.2 points [95% CI, −5.6 to −0.8]) vs the conscious sedation group (mean NIHSS score, 17.2 at admission vs 13.6 after 24 hour; difference, −3.6 points [95% CI, −5.5 to −1.7]); mean difference between groups, −0.4 (95% CI, −3.4 to 2.7; P = .82). Of 47 prespecified secondary outcomes analyzed, 41 showed no significant differences. In the general anesthesia vs the conscious sedation group, substantial patient movement was less frequent (0% vs 9.1%; difference, 9.1%; P = .008), but postinterventional complications were more frequent for hypothermia (32.9% vs 9.1%; P < .001), delayed extubation (49.3% vs 6.5%; P < .001), and pneumonia (13.7% vs 3.9%; P = .03). More patients were functionally independent (unadjusted mRS score, 0 to 2 after 3 months [37.0% in the general anesthesia group vs 18.2% in the conscious sedation group P = .01]). There were no differences in mortality at 3 months (24.7% in both groups).CONCLUSIONS AND RELEVANCE Among patients with acute ischemic stroke in the anterior circulation undergoing thrombectomy, conscious sedation vs general anesthesia did not result in greater improvement in neurological status at 24 hours. The study findings do not support an advantage for the use of conscious sedation.

Background Stroke thrombolysis with alteplase is currently recommended 0-4•5 h after stroke onset. We aimed to determine whether perfusion imaging can identify patients with salvageable brain tissue with symptoms 4•5 h or more from stroke onset or with symptoms on waking who might benefit from thrombolysis.Methods In this systematic review and meta-analysis of individual patient data, we searched PubMed for randomised trials published in English between Jan 1, 2006, and March 1, 2019. We also reviewed the reference list of a previous systematic review of thrombolysis and searched ClinicalTrials.gov for interventional studies of ischaemic stroke. Studies of alteplase versus placebo in patients (aged ≥18 years) with ischaemic stroke treated more than 4•5 h after onset, or with wake-up stroke, who were imaged with perfusion-diffusion MRI or CT perfusion were eligible for inclusion. The primary outcome was excellent functional outcome (modified Rankin Scale [mRS] score 0-1) at 3 months, adjusted for baseline age and clinical severity. Safety outcomes were death and symptomatic intracerebral haemorrhage. We calculated odds ratios, adjusted for baseline age and National Institutes of Health Stroke Scale score, using mixed-effects logistic regression models. This study is registered with PROSPERO, number CRD42019128036. FindingsWe identified three trials that met eligibility criteria: EXTEND, ECASS4-EXTEND, and EPITHET. Of the 414 patients included in the three trials, 213 (51%) were assigned to receive alteplase and 201 (49%) were assigned to receive placebo. Overall, 211 patients in the alteplase group and 199 patients in the placebo group had mRS assessment data at 3 months and thus were included in the analysis of the primary outcome. 76 (36%) of 211 patients in the alteplase group and 58 (29%) of 199 patients in the placebo group had achieved excellent functional outcome at 3 months (adjusted odds ratio [OR] 1•86, 95% CI 1•15-2•99, p=0•011). Symptomatic intracerebral haemorrhage was more common in the alteplase group than the placebo group (ten [5%] of 213 patients vs one [<1%] of 201 patients in the placebo group; adjusted OR 9•7, 95% CI 1•23-76•55, p=0•031). 29 (14%) of 213 patients in the alteplase group and 18 (9%) of 201 patients in the placebo group died (adjusted OR 1•55, 0•81-2•96, p=0•66).Interpretation Patients with ischaemic stroke 4•5-9 h from stroke onset or wake-up stroke with salvageable brain tissue who were treated with alteplase achieved better functional outcomes than did patients given placebo. The rate of symptomatic intracerebral haemorrhage was higher with alteplase, but this increase did not negate the overall net benefit of thrombolysis.

IMPORTANCE General anesthesia during thrombectomy for acute ischemic stroke has been associated with poor neurological outcome in nonrandomized studies. Three single-center randomized trials reported no significantly different or improved outcomes for patients who received general anesthesia compared with procedural sedation. OBJECTIVE To detect differences in functional outcome at 3 months between patients who received general anesthesia vs procedural sedation during thrombectomy for anterior circulation acute ischemic stroke.