Silvia Schönenberger

Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial

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. Trial Registration clinicaltrials.gov Identifier: NCT02126085.

Stroke-Related Early Tracheostomy Versus Prolonged Orotracheal Intubation in Neurocritical Care Trial (SETPOINT): A Randomized Pilot Trial.

Background and Purpose— Optimal timing of tracheostomy in ventilated patients with severe stroke is unclear. We aimed to investigate feasibility, safety, and potential advantages of early tracheostomy in these intensive care unit (ICU) patients. Methods— This prospective, randomized, parallel-group, controlled, open, and outcome-masked pilot trial was conducted in neurological/neurosurgical ICUs of a university hospital. Patients with severe ischemic or hemorrhagic stroke and an estimated need for at least 2 weeks of ventilation were randomized to either early tracheostomy (within day 1–3 from intubation; early) or to standard tracheostomy (between day 7–14 from intubation if extubation could not be achieved or was not feasible; standard). The primary outcome was length of stay in the ICU; secondary outcomes were diverse aspects of the ICU course. Results— Sixty patients were randomized and analyzed. No differences were observed with regard to the primary outcome length of stay in the ICU (median 18 [interquartile range 16–28] versus 17 [interquartile range 13–22] days, median difference: 1 [−2 to 6]; P=0.38) or to most secondary outcomes, including adverse effects. Instead, use of sedatives (62% versus 42% of ICU stay, median difference 17.5 [3.3–29.2]; P=0.02), ICU mortality (ICU deaths 3 [10%] versus 14 [47%]; P<0.01) and 6-month mortality (deaths 8 [27%] versus 18 [60%]; P=0.02) were lower in the early group than in the standard group, respectively. Conclusions— Early tracheostomy in ventilated intensive care stroke patients is feasible, and safe, and presumably reduces sedation need. Whether the suggested benefits in mortality and outcome truly exist has to be determined by a larger multicenter trial. Clinical Trial Registration— http://www.clinicaltrials.gov. Unique identifier: NCT01261091.

Sedation vs. Intubation for Endovascular Stroke TreAtment (SIESTA) - a randomized monocentric trial.

Background The optimal peri-interventional management of sedation and airway for endovascular stroke treatment (EST) appears to be a crucial factor for treatment success. According to retrospective studies, the widely favored general anesthesia with intubation seems to be associated with poor functional outcome compared to a slightly sedated non-intubated condition (conscious sedation). Method SIESTA is a monocentric, prospective, randomized parallel-group, open-label treatment trial with blinded endpoint evaluation (PROBE design). The study compares the non-intubated with the intubated state in patients receiving endovascular treatment of acute ischemic anterior circulation stroke. The primary endpoint is early neurological improvement as by National Institutes of Health Stroke Scale (NIHSS) after 24 h (difference between NIHSS on admission and NIHSS after 24 h). Secondary endpoints include: functional outcome after three-months as by modified Rankin Scale (mRS), mortality, parameters of ventilation and critical care, feasibility, and safety, i.e. complications related to endovascular stroke treatment. Conclusion The aims of this study are to prospectively clarify whether the non-intubated state of conscious sedation is feasible, safe, and superior with regard to early neurological improvement compared to the intubated state of general anesthesia in patients receiving acute endovascular stroke treatment.

Early tracheostomy in ventilated stroke patients: Study protocol of the international multicentre randomized trial SETPOINT2 (Stroke-related Early Tracheostomy vs. Prolonged Orotracheal Intubation in Neurocritical care Trial 2).

Background Tracheostomy is a common procedure in long-term ventilated critical care patients and frequently necessary in those with severe stroke. The optimal timing for tracheostomy is still unknown, and it is controversial whether early tracheostomy impacts upon functional outcome. Method The Stroke-related Early Tracheostomy vs. Prolonged Orotracheal Intubation in Neurocritical care Trial 2 (SETPOINT2) is a multicentre, prospective, randomized, open-blinded endpoint (PROBE-design) trial. Patients with acute ischemic stroke, intracerebral hemorrhage or subarachnoid hemorrhage who are so severely affected that two weeks of ventilation are presumed necessary based on a prediction score are eligible. It is intended to enroll 190 patients per group (n = 380). Patients are randomized to either percutaneous tracheostomy within the first five days after intubation or to ongoing orotracheal intubation with consecutive weaning and extubation and, if the latter failed, to percutaneous tracheostomy from day 10 after intubation. The primary endpoint is functional outcome defined by the modified Rankin Scale (mRS, 0–4 (favorable) vs. 5 + 6 (unfavorable)) after six months; secondary endpoints are mortality and cause of mortality during intensive care unit-stay and within six months from admission, intensive care unit-length of stay, duration of sedation, duration of ventilation and weaning, timing and reasons for withdrawal of life support measures, relevant intracranial pressure rises before and after tracheostomy. Conclusion The necessity and optimal timing of tracheostomy in ventilated stroke patients need to be identified. SETPOINT2 should clarify whether benefits in functional outcome can be achieved by early tracheostomy in these patients.

Clinical Outcome After Mechanical Thrombectomy in Non-elderly Patients with Acute Ischemic Stroke in the Anterior Circulation: Primary Admission Versus Patients Referred from Remote Hospitals

Background and PurposeStroke networks have been installed to increase access to advanced stroke specific treatments like mechanical thrombectomy (MT). This concept often requires patients to be transferred to a comprehensive stroke center (CSC) offering MT. Do patient referral, transportation, and logistic effort translate into clinical outcomes comparable to patients admitted primarily to the CSC?Material and MethodsWe categorized 112 patients with acute ischemic stroke in the anterior circulation, who received MT at our institution, into primary admissions (A) and referrals from either local (B) or regional (C) hospitals, assessed the clinical outcome, and tested the impact of distance and delay of transportation from the referring remote hospital.ResultsThe median time from symptom onset to initial CT was similar in all groups (p = 0,939). Patients who were transferred to the CSC had significantly increasing median time between initial CT and MT (in minutes (interquartile range [IQR]); A: 83 [68–120]; B: 174 [159–208]; C: 220 [181–235]; p < 0.001) and median time between onset to MT (in minutes [IQR]; A: 178 [150–210]; B: 274 [238–349]; C: 293 [256–329]; p < 0.001).After 90 days of MT there was no significant difference in clinical outcome (modified Rankin Scale ≤ 2) between primary admitted and referred patients (p = 0.502).ConclusionClinical outcome in patients who received MT after transfer from either local or regional remote hospitals was not significantly worse than in patients primarily admitted to the CSC. In the event of an acute ischemic stroke patients living in urban or rural areas should, despite a possible delay, have access to MT.

Impact of thrombus length on recanalization and clinical outcome following mechanical thrombectomy in acute ischemic stroke

Purpose The impact of thrombus length on recanalization in IV thrombolysis for acute intracranial artery occlusion has been well studied. Here we analyzed the influence of thrombus length on the number of thrombectomy maneuvers needed for recanalization, intraprocedural complications, recanalization success, and clinical outcome after mechanical thrombectomy. Methods We retrospectively analyzed angiographic and clinical data from 72 consecutive patients with acute occlusion of the M1 segment of the middle cerebral artery who were treated with mechanical thrombectomy using stent retrievers. Successful recanalization was defined as a Thrombolysis in Cerebral Infarction score of 2b or 3. Good neurological outcome was defined as a modified Rankin Scale score of ≤2 at 90 days after stroke onset. Results Mean thrombus length was 13.4±5.2 mm. Univariate binary logistic regression did not show an association of thrombus length with the probability of a good clinical outcome (OR 0.95, 95% CI 0.84 to 1.03, p=0.176) or successful recanalization (OR 0.92, 95% CI 0.81 to 1.05, p=0.225). There was no significant correlation between thrombus length and the number of thrombectomy maneuvers needed for recanalization (p=0.112). Furthermore, thrombus length was not correlated with the probability of intraprocedural complications (p=0.813), including embolization in a new territory (n=3). Conclusions In this study, thrombus length had no relevant impact on recanalization, neurological outcome, or intraprocedural complications following mechanical thrombectomy of middle cerebral artery occlusions. Therefore, mechanical thrombectomy with stent retrievers can be attempted with large clots.

Mechanical thrombectomy using a combined CT/C-arm X-ray system

Background Mechanical thrombectomy (MT) using stent-retrievers has been proven to be a safe and effective treatment in acute ischemic stroke (AIS), particularly in large vessel occlusion. Other than patient characteristics, time to recanalization is the most important factor linked to outcome. MT is usually performed in a dedicated angiography suite using a floor- and/or ceiling-mounted biplane angiographic system. Here we report our first experience of MT with a new combined CT and mobile C-arm X-ray device setup. Methods Patients with AIS underwent stroke imaging (non-contrast enhanced CT, CT perfusion, and CT angiography) using a commercially available 64-slice CT scanner which was modified for combined use with a C-arm system. In patients with large vessel occlusion, MT was conducted without further patient transfer within the CT imaging suite using a mobile C-arm X-ray device equipped with a 30×30 cm (12×12 inch), 1.5×1.5 k full-view flat detector which was positioned between the gantry and patient table. The safety and feasibility of this new system was assessed in preliminary patients. Results Angiographic imaging quality of the mobile C-arm was feasible and satisfactory for diagnostic angiography and MT. Using this setup, time between stroke imaging and groin puncture (picture-to-puncture time) was reduced by up to 35 min (including time for preparation of the patient such as intubation). Conclusions MT using a combined CT/C-arm system is safe and feasible. The potential advantages, particularly time saving and ensuing improvement in patient outcome, need to be assessed in a larger study.

Effect of General Anesthesia versus Conscious Sedation for Stroke Thrombectomy on Angiographic Workflow in a Randomized Trial: A Post Hoc Analysis of the SIESTA Trial

Purpose To investigate whether the sedation mode (ie, conscious sedation [CS] vs general anesthesia [GA]) affects the angiographic workflow applied for treatment of endovascular stroke in a post hoc analysis of a recent randomized controlled trial, Sedation versus Intubation for Endovascular Stroke Treatment (SIESTA). Materials and Methods SIESTA was an institutional review board-approved, single-center, prospective, randomized, parallel-group, open-label treatment trial with a blinded end-point evaluation to compare GA with CS for treatment of endovascular stroke in 73 and 77 patients, respectively. By using descriptive data from SIESTA, the influence of the mode of sedation on angiographic workflow during treatment for endovascular stroke (eg, procedure times) and other radiologic outcome parameters (eg, radiation exposure) were analyzed. The time between angiographic key steps for patients who underwent GA and CS was evaluated with t tests. P values were corrected for false discovery rate. Results The median time from groin puncture to first intracranial flow restoration with CS was 47 minutes (interquartile range [IQR], 29-70 minutes), and for GA, it was 41 minutes (IQR, 28-60 minutes) (P = .546). The median time to the end of angiography with CS was 104 minutes (IQR, 75-150 minutes), and with GA, it was 73 minutes (IQR, 53-125 minutes) (P = .052). Fluoroscopy time with CS was 49 minutes (IQR, 25-85 minutes), and with GA, it was 35 minutes (IQR, 20-74 minutes) (P = .098). The times were comparable in both groups for these measures. The time from groin puncture to the final angiographic result with GA, at 72 minutes (IQR, 45-109 minutes) was shorter than that with CS, at 98 minutes (IQR, 64-135 minutes) (P = .048). Conclusion This post hoc analysis of the single-center SIESTA trial revealed that time from groin puncture to final angiographic result was shorter with patients under GA than that with patients under CS.

Association of Blood Pressure With Short- and Long-Term Functional Outcome After Stroke Thrombectomy: Post Hoc Analysis of the SIESTA Trial

Background and Purpose— Outcome after mechanical thrombectomy for ischemic stroke may be influenced by blood pressure (BP). This study aims to assess the association of BP changes during general anesthesia versus conscious sedation with functional outcome after mechanical thrombectomy. Methods— SIESTA (Sedation vs Intubation for Endovascular Stroke Treatment) was a monocentric randomized trial of general anesthesia versus conscious sedation during mechanical thrombectomy involving BP target protocols. In this post hoc analysis, BP measurements were divided into 4 phases: preintervention, prerecanalization, postrecanalization, and postintervention. We examined the association between BP and functional outcomes (defined by improvement of 24-hour National Institutes of Health Stroke Scale [NIHSS] and 3-month modified Rankin Scale). Results— We found no association between the difference in systolic BP, diastolic BP, and mean arterial pressure from baseline to the different phases of intervention and NIHSS change after 24 hours. Only baseline diastolic BP was associated with a reduced improvement in NIHSS (&bgr;=0.17, P<0.01). There was no association of BP drops with a change in modified Rankin Scale at 3 months. About sedation, only baseline mean arterial pressure preintervention revealed significant associations (&bgr;=0.16, P<0.01) with less change in 24-hour NIHSS in conscious sedation group. Otherwise, there was no association for differences of any of the BP measurements with a change in 24-hour NIHSS and long-term functional outcome either in general anesthesia or the conscious sedation group when analyzed separately, consistent with our findings in the entire cohort. Doses of propofol (&bgr;=0.84, P=0.04) and norepinephrine (&bgr;=1.87, P=0.01) administered during intervention before recanalization were associated with reduced improvement of NIHSS at 24 hours. Conclusions— In a setting, where both sedation regimes general anesthesia and conscious sedation were performed according to strict protocols directed at avoiding BP extremes, our findings suggest that peri-interventional BP drops were not associated with either early neurological improvement or long-term functional outcome. Clinical Trial Registration— URL: https://www.clinicaltrials.gov. Unique identifier: NCT02126085.

Influence of a combined CT/C-arm system on periprocedural workflow and procedure times in mechanical thrombectomy

ObjectiveTo achieve the fastest possible workflow in ischaemic stroke, we developed a CT/C-arm system, which allows imaging and endovascular treatment on the same patient table.MethodsThis prospective, monocentric trial was conducted between October 2014 and August 2016. Patients received stroke imaging and mechanical thrombectomy under general anaesthesia (GA) or conscious sedation (CS) using our combined setup comprising a CT-scanner and a mobile C-arm X-ray device. Primary endpoint was time between stroke imaging and groin puncture. We compared periprocedural workflow and procedure times with the literature and a matched patient cohort treated with a biplane angiographic system before installation of the CT/C-arm system.ResultsIn 50 patients with acute ischaemic stroke due to large-vessel occlusion in the anterior circulation, comparable recanalization rates were achieved by using the CT/C-arm setup (TICI2b-3:CT/C-arm-GA: 85.7%; CT/C-arm-CS: 90.9%; Angiosuite: 78.6%; p = 0.269) without increasing periprocedural complications. Elimination of patient transport resulted in a significant reduction of the time between stroke imaging and groin puncture: median, min (IQR): CT/C-arm-GA: 43 (35–52); CT/C-arm-CS: 39 (28–49); Angiosuite: 64 (48–74); p < 0.0001.ConclusionThe combined CT/C-arm system allows comparable recanalization rates as a biplane angiographic system and accelerates the start of the endovascular stroke treatment.Key Points• The CT/C-arm setup reduces median time from stroke imaging to groin puncture.• Mechanical thrombectomy using a C-arm device is feasible without increasing peri-interventional complications.• The CT/C-arm setup might be a valuable fallback solution for emergency procedures.• The CT/C-arm setup allows immediate control CT images during and after treatment.