Anesthesia Management in Endovascular Therapy for Ischemic Stroke (AMETIS)

Anesthesia Management in Endovascular Therapy for Ischemic Stroke: A Multicenter Randomised Study

Objective of the study: to assess whether pharmacological sedation or general anesthesia for treatment of anterior circulation ischemic stroke with endovascular mechanical thrombectomy is associated with difference in morbidity (neurological outcome and peri-procedural complications).

Study Overview

• Status: Completed
• Conditions: Stroke; Anesthesia; Conscious Sedation; Thrombectomy
• Intervention / Treatment: Procedure: General anaesthesia; Procedure: Conscious Sedation

Detailed Description

Since 2015, the management of anterior acute ischemic stroke (AIS) involves endovascular treatment with mechanical thrombectomy (MT). This urgent, difficult and uncomfortable procedure in frail patients requires multidisciplinary care ideally involving neurologists, interventional neuroradiologists and anesthesiologists.

Two anesthetic strategies are currently used: pharmacologic sedation in spontaneous ventilation or general anesthesia with tracheal intubation. General anesthesia provides strict immobility, protects the airway and avoids emergency intubation in case of severe procedural complication (notably vomiting and aspiration). Sedation is a frequently used alternative because of (1) a rapid execution which could reduce delay to reperfusion, (2) a lower risk of blood pressure drop that may compromise cerebral blood flow in the penumbra area, (3) the theoretical capacity to assess neurological status during the procedure and (4) the supposed risk of complications associated with mechanical ventilation and intravenous anesthestics on brain metabolism. Nevertheless, sedation exposes to dramatic complications in case of patient agitation and movements.

The choice of the ideal anesthesic management is still lacking. Old retrospective studies seemed to favor sedation with worst neurological outcome associated with general anesthesia. Nevertheless, these datas suffered methodological issues with selection bias: more severe patients based on NIHSS score were rather treated with general anesthesia and blood pressure was not controlled. Recent studies that demonstrated the benefit of MT did not include a specific anesthetic protocol and none of the studies currently available included a blood pressure management protocol that appears to be an essential component of cerebral perfusion. A subgroup analysis of the MR Clean study, including patients with an identical initial NIHSS score, did not find benefit from MT in patients with general anesthesia compared to those receiving sedation. Finally, authors concluded that performing a MT under general anesthesia would significantly lengthen the reperfusion delay and nullify the benefit of MT.

The prospective, randomized, single-center SIESTA trial, conducted in 150 patients with an anterior circulation AIS, found no difference in the early neurological improvement (primary endpoint), assessed on the change in NIHSS score between admission and the 24th hour, between the conscious sedation group and the general anesthesia group. There were a tendency for a better 3-month neurological outcome in the general anesthesia group (37% vs 18% of patients with a Modified Rankin score of 0-2 in the general anesthesia and conscious sedation groups respectively), but it was not possible to conclude due to a lack of statistical power.

Due to the increasing number of patients eligible for endovascular MT and the potential implication of these two anesthetic management on the functional outcome, a study comparing general anesthesia and sedation during a MT seems essential as specified in the recent updated American Stroke Association guidelines.

The objective of this study is to assess whether sedation or general anesthesia during endovascular treatment with mechanical thrombectomy is associated with a difference in morbidity (neurological outcome and peri-procedural complications), in anterior circulation AIS.

• Study Type: Interventional
• Enrollment (Actual): 332
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Auvergne
    • Clermont-Ferrand, Auvergne, France, 63003
      • CHU de Clermont-Ferrand

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Acute anterior circulation ischemic stroke (terminal portion of the internal carotid artery, middle cerebral artery), with indication for radiological mechanical thrombectomy assessed by the neurology / neuroradiology team
• Over 18 years of age
• Benefiting from an affiliation to the French Social Security system
• Patient or familly informed consent. In case of patient incapacity and no family present, and due to the emergency of the procedure, the patient may be included on the sole decision of the investigator (emergency procedure with subsequent differed consent).

Exclusion Criteria:

• Altered vigilance defined by score ≥ 2 at item 1a "level of consciousness" of the NIHSS score
• Altered previous autonomy, defined by a modified Rankin score (mRS)> 1
• Acute ischemic stroke of posterior circulation or anterior cerebral artery
• Associated brain haemorrhage
• Pregnant or nursing women
• Patient under law protection
• Stroke complicating another acute illness or postoperative stroke.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: General anaesthesia; In the general anesthesia group, rapid sequence induction is used. Conduction of general anesthesia and drugs used are left to the expertise of each investigating center. Systolic blood pressure has to be maintained between 140 and 180 mmHg with an intravenous norepinephrine infusion if necessary, tele-expiratory carbon dioxyde concentration (EtCO2) has to be maintained between 30 and 35 mmHg and SpO2 has to be maintained between 94 and 98 %.	Procedure: General anaesthesia; Procedure in which patients are induced into an unconscious state through use of various medications so that they do not feel pain during surgery
Active Comparator: Conscious Sedation; In the conscious sedation group, drugs choice as well as pharmacological modulation will be left to the expertise of each investigating center. A sedation level between 0 and -3 with spontaneous breathing will be targeted, using the Richmond Agitation Sedation Scale (RASS) score validated in French. The lightest sedation level will be targeted, i.e. minimal to moderate sedation according to the US recommendations for sedation / analgesia. Systolic blood pressure will be maintained between 140 and 180 mmHg with an intravenous norepinephrine infusion if necessary and SpO2 will be maintained between 94 and 98%.	Procedure: Conscious Sedation; A drug-induced depression of consciousness during which patients respond purposefully to verbal commands, either alone or accompanied by light tactile stimulation. No interventions are required to maintain a patent airway. (From: American Society of Anesthesiologists Practice Guidelines)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
composite of functional independence at 3 months and absence of medical complication occurring by day 7 after endovascular therapy for anterior circulation AIS	The primary outcome measure is a composite of functional independence at 3 months and absence of medical complication occurring by day 7 after endovascular therapy for anterior circulation AIS. Functional independence is defined as a mRS score 0 to 2 by day 90. Medical complications are defined as intervention-associated arterial perforation or dissection, pneumonia or myocardial infarction or acute cardiogenic pulmonary oedema or malignant stroke evolution occurring by day 7	Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ordinal score on the mRS by day 90		at day 90
Functional independence by day 90 defined as a mRS score 0-2		at day 90
Excellent recovery by day 90 defined as a mRS score 0-1		at day 90
Moderate recovery by day 90 defined as a mRS score 0-3		at day 90
Shift analysis of day 90 mRS adjusted for initial prognostic factors	(baseline mRS, age, initial NIHSS, carotid top occlusion)	at day 90
Good recovery defined with sliding dichotomy responder analysis relating day 90 mRS with baseline NIHSS score: mRS 0 for NIHSS ≤ 7; mRS 0-1 for NIHSS 8-14; mRS 0-2 for NIHSS > 14		at day 90
Intraprocedural hemodynamic and ventilatory conditions and complications defined as hypotension, blood pressure variability, hypoxemia and aspiration		at day 90
Intervention-associated vessel and others complications defined as arterial dissection or perforation, groin hematoma, embolization in another arterial territory		at day 90
Door to groin puncture delay		at day 90
Door to reperfusion delay		at day 90
Successful reperfusion defined by the modified Treatment In Cerebral Ischemia (mTICI) reperfusion scale of 2b or 3 (with a grade of 2b or 3 indicating reperfusion of > 50% of the affected territory)		at day 90
NIHSS by day 1 and day 7		by day 1 and day 7
Stroke unit and hospital length of stay		at day 90
Medical complications by day 7 defined as pneumonia, acute cardiogenic pulmonary oedema, myocardial infarction, extra pulmonary infection, venous thromboembolism, new event of AIS, epilepsy, gastrointestinal bleeding or other symptomatic bleeding		at day 7
Malignant stroke evolution by day 7		by day 7
Symptomatic intracranial haemorrhage by day 7 defined as brain haemorrhage on imaging associated with an increase of at least 4 points in the NIHSS score		by day 7
Unexpected intensive care unit admission by day 7		by day 7
Mortality by day 7 and day 90		by day 7 and day 90
Procedural feasibility score estimated by the radiologist and the anaesthesiologist and patient acceptability score		by day 7 and day 90

Collaborators and Investigators

• Sponsor: University Hospital, Clermont-Ferrand
• Collaborators: Direction Générale de l'Offre de Soins
• Investigators: Principal Investigator: Russel Chabanne, MD, CHU de Clermont-Ferrand

Publications and helpful links

General Publications

• Berkhemer OA, Fransen PS, Beumer D, van den Berg LA, Lingsma HF, Yoo AJ, Schonewille WJ, Vos JA, Nederkoorn PJ, Wermer MJ, van Walderveen MA, Staals J, Hofmeijer J, van Oostayen JA, Lycklama a Nijeholt GJ, Boiten J, Brouwer PA, Emmer BJ, de Bruijn SF, van Dijk LC, Kappelle LJ, Lo RH, van Dijk EJ, de Vries J, de Kort PL, van Rooij WJ, van den Berg JS, van Hasselt BA, Aerden LA, Dallinga RJ, Visser MC, Bot JC, Vroomen PC, Eshghi O, Schreuder TH, Heijboer RJ, Keizer K, Tielbeek AV, den Hertog HM, Gerrits DG, van den Berg-Vos RM, Karas GB, Steyerberg EW, Flach HZ, Marquering HA, Sprengers ME, Jenniskens SF, Beenen LF, van den Berg R, Koudstaal PJ, van Zwam WH, Roos YB, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW; MR CLEAN Investigators. A randomized trial of intraarterial treatment for acute ischemic stroke. N Engl J Med. 2015 Jan 1;372(1):11-20. doi: 10.1056/NEJMoa1411587. Epub 2014 Dec 17. Erratum In: N Engl J Med. 2015 Jan 22;372(4):394.
• Jovin TG, Chamorro A, Cobo E, de Miquel MA, Molina CA, Rovira A, San Roman L, Serena J, Abilleira S, Ribo M, Millan M, Urra X, Cardona P, Lopez-Cancio E, Tomasello A, Castano C, Blasco J, Aja L, Dorado L, Quesada H, Rubiera M, Hernandez-Perez M, Goyal M, Demchuk AM, von Kummer R, Gallofre M, Davalos A; REVASCAT Trial Investigators. Thrombectomy within 8 hours after symptom onset in ischemic stroke. N Engl J Med. 2015 Jun 11;372(24):2296-306. doi: 10.1056/NEJMoa1503780. Epub 2015 Apr 17.
• Goyal M, Demchuk AM, Menon BK, Eesa M, Rempel JL, Thornton J, Roy D, Jovin TG, Willinsky RA, Sapkota BL, Dowlatshahi D, Frei DF, Kamal NR, Montanera WJ, Poppe AY, Ryckborst KJ, Silver FL, Shuaib A, Tampieri D, Williams D, Bang OY, Baxter BW, Burns PA, Choe H, Heo JH, Holmstedt CA, Jankowitz B, Kelly M, Linares G, Mandzia JL, Shankar J, Sohn SI, Swartz RH, Barber PA, Coutts SB, Smith EE, Morrish WF, Weill A, Subramaniam S, Mitha AP, Wong JH, Lowerison MW, Sajobi TT, Hill MD; ESCAPE Trial Investigators. Randomized assessment of rapid endovascular treatment of ischemic stroke. N Engl J Med. 2015 Mar 12;372(11):1019-30. doi: 10.1056/NEJMoa1414905. Epub 2015 Feb 11.
• Campbell BC, Mitchell PJ, Kleinig TJ, Dewey HM, Churilov L, Yassi N, Yan B, Dowling RJ, Parsons MW, Oxley TJ, Wu TY, Brooks M, Simpson MA, Miteff F, Levi CR, Krause M, Harrington TJ, Faulder KC, Steinfort BS, Priglinger M, Ang T, Scroop R, Barber PA, McGuinness B, Wijeratne T, Phan TG, Chong W, Chandra RV, Bladin CF, Badve M, Rice H, de Villiers L, Ma H, Desmond PM, Donnan GA, Davis SM; EXTEND-IA Investigators. Endovascular therapy for ischemic stroke with perfusion-imaging selection. N Engl J Med. 2015 Mar 12;372(11):1009-18. doi: 10.1056/NEJMoa1414792. Epub 2015 Feb 11.
• Saver JL, Goyal M, Bonafe A, Diener HC, Levy EI, Pereira VM, Albers GW, Cognard C, Cohen DJ, Hacke W, Jansen O, Jovin TG, Mattle HP, Nogueira RG, Siddiqui AH, Yavagal DR, Baxter BW, Devlin TG, Lopes DK, Reddy VK, du Mesnil de Rochemont R, Singer OC, Jahan R; SWIFT PRIME Investigators. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke. N Engl J Med. 2015 Jun 11;372(24):2285-95. doi: 10.1056/NEJMoa1415061. Epub 2015 Apr 17.
• Tosello R, Riera R, Tosello G, Clezar CN, Amorim JE, Vasconcelos V, Joao BB, Flumignan RL. Type of anaesthesia for acute ischaemic stroke endovascular treatment. Cochrane Database Syst Rev. 2022 Jul 20;7(7):CD013690. doi: 10.1002/14651858.CD013690.pub2.
• Powers WJ, Derdeyn CP, Biller J, Coffey CS, Hoh BL, Jauch EC, Johnston KC, Johnston SC, Khalessi AA, Kidwell CS, Meschia JF, Ovbiagele B, Yavagal DR; American Heart Association Stroke Council. 2015 American Heart Association/American Stroke Association Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2015 Oct;46(10):3020-35. doi: 10.1161/STR.0000000000000074. Epub 2015 Jun 29.
• Berkhemer OA, van den Berg LA, Fransen PS, Beumer D, Yoo AJ, Lingsma HF, Schonewille WJ, van den Berg R, Wermer MJ, Boiten J, Lycklama A Nijeholt GJ, Nederkoorn PJ, Hollmann MW, van Zwam WH, van der Lugt A, van Oostenbrugge RJ, Majoie CB, Dippel DW, Roos YB; MR CLEAN investigators. The effect of anesthetic management during intra-arterial therapy for acute stroke in MR CLEAN. Neurology. 2016 Aug 16;87(7):656-64. doi: 10.1212/WNL.0000000000002976. Epub 2016 Jul 15.
• Schonenberger S, Uhlmann L, Hacke W, Schieber S, Mundiyanapurath S, Purrucker JC, Nagel S, Klose C, Pfaff J, Bendszus M, Ringleb PA, Kieser M, Mohlenbruch MA, Bosel J. Effect of Conscious Sedation vs General Anesthesia on Early Neurological Improvement Among Patients With Ischemic Stroke Undergoing Endovascular Thrombectomy: A Randomized Clinical Trial. JAMA. 2016 Nov 15;316(19):1986-1996. doi: 10.1001/jama.2016.16623. Erratum In: JAMA. 2017 Feb 7;317(5):538.
• Chabanne R, Begard M, Cazenave L, Pereira B. New paradigm shift in perioperative medicine: General anaesthesia finally better than procedural sedation for anterior circulation stroke thrombectomy? Anaesth Crit Care Pain Med. 2019 Dec;38(6):585-587. doi: 10.1016/j.accpm.2019.10.005. No abstract available.
• Chabanne R, Fernandez-Canal C, Degos V, Lukaszewicz AC, Velly L, Mrozek S, Perrigault PF, Molliex S, Tavernier B, Dahyot-Fizelier C, Verdonk F, Caumon E, Masgrau A, Begard M, Chabert E, Ferrier A, Jaber S, Bazin JE, Pereira B, Futier E; ANARLF Network and the AMETIS study group. Sedation versus general anaesthesia in endovascular therapy for anterior circulation acute ischaemic stroke: the multicentre randomised controlled AMETIS trial study protocol. BMJ Open. 2019 Sep 13;9(9):e027561. doi: 10.1136/bmjopen-2018-027561.

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2017
• Primary Completion (Actual): May 13, 2020
• Study Completion (Actual): June 30, 2020

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 24, 2017
• First Posted (Actual): July 25, 2017

Study Record Updates

• Last Update Posted (Actual): September 30, 2020
• Last Update Submitted That Met QC Criteria: September 28, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• Keywords: Stroke; Thrombectomy; Anesthesia; Conscious sedation; Anesthesia or Conscious sedation for Thrombectomy for Stroke
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke; Physiological Effects of Drugs; Central Nervous System Depressants; Anesthetics
• Other Study ID Numbers: CHU-343; 2017-0303001-90 (Other Identifier: 2017-0303001-90)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No