GA vs. CS for Endovascular Stroke Therapy
GA vs. CS for Endovascular Stroke Therapy
After a stroke caused by a blockage (clot) in a blood vessel in the brain, patients may have
 the clot removed by threading a catheter from the groin up to the affected area of the brain.
 An anesthesiologist is involved in the patient's care during this procedure to maximize
 patient safety and procedural efficiency. The options for anesthesia for this procedure are
 general anesthesia (where the patient is unconscious) or sedation (where the patient is in a
 relaxed, calm, sleepy condition). Currently, it is unclear which of these anesthetic options
 contributes to the best patient outcome. The investigators would like to investigate whether
 or not one method of anesthesia (general or sedation) is better to use than the other when
 removing the clot.
Rationale: Stroke is a leading cause of adult morbi-mortality worldwide. Intravenous (IV)
 recombinant tissue plasminogen activator (rtTPA) was the only therapeutic option for many
 years. After the publication of five randomized controlled trials, guidelines for stroke
 treatment were updated and released in 2015. According to these guidelines, in addition to IV
 rtTPA, endovascular therapy (EVT) for acute ischemic stroke (AIS), secondary to proximal
 intracranial arterial occlusion, has become established as an international standard of care
 (Avitsian & Machado, 2016). Management of patients undergoing stroke is complex due to the
 association of acute neurological physiological changes and pre-existing co-morbidities. To
 facilitate efficient and safe delivery of endovascular treatment, patients require anesthetic
 intervention in the form of sedation or general anesthesia (GA). The choice of anesthetic
 technique is often guided by individual patient factors and personal clinician practice
 (Dhakal, Diaz-Gomez, & Freeman, 2015). Two recent meta-analyses (Brinjikji et al., 2015) have
 found an association of better functional outcome related to endovascular procedures
 performed under sedation compared to general anesthesia. The interpretation of current data
 is challenging as most studies are retrospective and performed under direction of
 non-anesthetists with poor definition of anesthetic techniques. A prospective controlled
 randomized trial is required to demonstrate the influence of anesthesia techniques on
 functional outcome. Prior to commencing this large trial, the investigators will execute a
 feasibility study (GASTROKE-pilot), which is outlined here. Following confirmation of
 feasibility, the full prospective randomized controlled trial will take place using the same
 study methodology.

 The objectives of the pilot study are: 1) To determine feasibility of the methods and
 procedures for a proposed prospective randomized controlled trial. Specifically, to determine
 if randomization can be reliably performed in a timely fashion to facilitate inclusion in the
 study. Note: EVT will not be delayed beyond institutional temporal limits to allow
 recruitment or randomization of potential participants. 2) To determine if anesthesia for EVT
 can be reliably delivered according to the standardized protocol. 3) To determine if
 post-treatment follow-up of functional outcome can be reliably performed according to a
 standardized methodology. If the pilot study demonstrates feasibility, the investigators will
 proceed with a much larger RCT.

 Methodology: Randomization: Patients identified by the Acute Stroke team as candidates for
 EVT will be referred to the study anesthesia team for consideration as study participants.
 Only after anesthetic pre-procedural assessment is complete, as per usual standard of care,
 and clinical uncertainty exists as to the best anesthetic management will the patient be
 randomized. Sequence generation: Randomization will be performed using REDCap to allow
 central randomization from any hospital computer with internet access. The blocked
 randomization sequence list will be created in STATA. The randomization instrument will be
 created in REDCap separate to the data collection tool to ensure blinding allocation is
 maintained. All treating consultant anesthetists will have access to the REDCap randomization
 instrument. User rights will be set so that these clinicians do not have access to
 participant follow-up data. Details of each procedure (GA or sedation) are outlined below.
 The attending anesthetist will log-on to REDCap and access the Randomization tool. This
 process will take 2-3 minutes once trained in the randomization process.

 Blinding: Both patient and treating physician will be aware of the treatment assignment.
 Post-procedural functional outcomes will be performed by a dedicated clinician blinded to the
 treatment assignment. Interventions: Physiological Parameters: Target Values (Talke et al.,
 2014) • Oxygenation: Maintain SpO2 > 92% and PaO2 > 60 mmHg. • Ventilation: Maintain
 normocapnia, PaCO2 35-45 mmHg under GA. Avoid respiratory-induced hypercarbia during sedation
 • Hemodynamics: Systolic blood pressure > 140 mmHg and < 180 mmHg. Diastolic blood pressure <
 105 mmHg. • Temperature: Maintain normothermia, T 35°C - 37°C. • Glucose control: Maintain
 blood glucose concentration 4.0 - 8.0 mmol/L. If blood glucose levels greater than 8 mmol/L
 (140 mg/dL) IV insulin infusion to be commenced. Blood glucose concentration to be repeated
 after 30 minutes. Hypoglycemia as defined by blood glucose < 3 mmol/L (50 mg/dL) should be
 treated with IV 10-20% glucose. General Anesthesia Protocol: (Melinda J. Davis, Cynthia R.
 Campos-Herrera, & David P. Archer, 2012; Powers et al., 2015; Talke et al., 2014) 1.
 Monitoring • American Society of Anesthesiologists (ASA) standard (non-invasive blood
 pressure (BP), electrocardiogram (ECG), oxygen saturation (SpO2), end-tidal carbon dioxide
 (ETCO2), temperature and neuromuscular monitoring (NMM)) • Invasive BP: direct measure of the
 arterial BP, with continuous pressure transduction and waveform display is the standard for
 blood pressure monitoring in AIS. It allows continuous BP assessment and provides reliable
 vascular access for frequent sampling. However, benefits of invasive arterial monitoring are
 null if the procedure itself delays reperfusion therapy (Saver, 2006). There is no consensus
 regarding timing of arterial access in EVT for AIS. This is our protocol: • 1 attempt with
 the patient awake • Maximum of 2 more attempts with the patient under anesthesia • Stop after
 a total of 3 attempts, or when the radiologist has access to the femoral artery. 2. Induction
 of anesthesia. 3. Neuromuscular paralysis. 4. Endotracheal intubation. 5. Positive pressure
 ventilation: ETCO2 range: 35-40 mmHg until arterial partial pressure of carbon dioxide
 (PaCO2) is obtained and the gap is measured. 6. Volatile anesthesia with sevoflurane or
 desflurane to a target age-compensated minimum alveolar concentration (MAC) > 0.5 but =
 1(Sivasankar et al., 2016) 7. Vasopressor support: If the systolic BP decreases more than 20%
 from pre-anesthetic value or is lower than 140 mmHg, the patient will receive vasopressor
 support as IV phenylephrine and/or ephedrine, titrated to effect. 8. Hypertension management:
 For systolic BP > 180 mmHg, IV labetalol will be administered, titrated to effect. 9.
 Arterial blood gas sampling to be performed at the earliest convenience after induction of
 anesthesia. Clinical goals are outlined above. 10. Temperature monitoring wit esophageal
 temperature probe. 11. Antagonism of neuromuscular blockade at the end of the procedure. The
 train of four should be = 0.9 prior to extubation (Hassan et al., 2012; Murphy GS, 2015). 12.
 Transfer the patient to the post-anesthesia care unit (PACU). Sedation Protocol: 1.
 Monitoring • ASA standard (non-invasive BP, ECG, SpO2, T, respiratory rate (RR), and ETCO2) •
 Invasive BP: a direct measure of the arterial blood pressure, • Maximum 3 attempts. Stop
 after a total of 3 attempts, or when the radiologist has access to the femoral artery. 2.
 Administer oxygen by nasal prongs or facial mask to achieve a target Sp02 = 92%. 3. Commence
 sedation: Remifentanil: 0.01-0.06 micrograms/kilogram/minute, titrated to effect. (Janssen et
 al., 2016) 4. Monitor RR. Decrease sedative infusion rate if RR < 6. 5. Vasopressor support:
 If the systolic BP decreases more than 20% from pre-anesthetic value or if is lower than 140
 mmHg, the patient will receive vasopressor support as IV phenylephrine and/or ephedrine,
 titrated to effect. 6. Hypertension management: For systolic BP > 180 mmHg, IV labetalol will
 be administered, titrated to effect. 7. Arterial blood gas sampling to be performed at the
 earliest convenience after induction of anesthesia. Clinical goals are outlined above. 8.
 Temperature monitoring with axillary temperature probe. 9. Transfer the patient to the PACU.

 Conversion of sedation to GA: Patients randomized to receive EVT under sedation will be
 converted to GA in cases of emergency (vascular injury), reduced level of consciousness
 (GCS<8), loss of airway reflexed, respiratory failure with rise in EtCO2 and agitation
 precluding safe conduct of EVT.

 Post-Procedural Follow-up:This will be conducted by a clinical research assistant who is
 blinded to the study intervention. The specifics of the follow-up procedure are detailed
 below: Day1: The NIHSS clinical scoring tool will be performed on the stoke inpatient unit.
 This scale is a validated tool to objectively quantify disability following a stroke. The
 tool entails assessment of level of consciousness, motor function, sensation, coordination,
 speech and concentration. Currently, this tool is utilised at LHSC as part of the follow-up
 for AIS post-procedural days 1. Day 1-2: All patients will have a CT angiogram and MRI within
 24-48 hours post-procedure as per usual standard of care. From these scans, the Thrombolysis
 in Cerebral Infarction (TICI) scale and final infarct volume will be calculated. Day 7: The
 NIHSS will be repeated to quantify ongoing disability. Day 90: As per the usual standard of
 care, all patient discharged from hospital will have a 3 month post-stroke outpatient
 follow-up appointment. The mRS and NIHSS will be repeated by the clinical research assistant
 at the neurological outpatient appointment. Should the appointment be delayed longer than 3
 months post-stroke, a telephone call will be made by the clinical research assistant to
 determine the mRS. If the patient remains an inpatient at 90 days post-stroke, the electronic
 record will be accessed to gain the required information to calculate the mRS
Inclusion Criteria: All patients with ischemic stroke who:

 -  are greater than 18 years of age

 -  considered to be a candidate for endovascular therapy by the London Health Sciences
 Stroke team

 -  presenting within the first 8 hours after symptom onset EXCEPT THOSE for whom general
 anesthesia is thought to be clearly indicated or contraindicated, by the attending
 anesthesiologist.

 Exclusion Criteria:

 -  Patients in whom the attending anesthesiologist considered that there was a clear
 indication for either GA or sedation