Clinical trial NCT05051397: CO2 Modulation in Endovascular Thrombectomy for Acute Ischemic Stroke
Official title: Evaluation of the Effect of Moderate and Controlled Hypercapnia on Ischemic Penumbra Vascular Collaterality During General Anesthesia for Anterior Circulation Acute Ischemic Stroke Mechanical Thrombectomy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Ischemic Stroke, Acute
Thrombectomy
Anesthesia, General
Cerebrovascular Circulation
Carbon Dioxide
Keywords: mechanical thrombectomy
large vessel occlusion stroke
carbon dioxide tension
cerebral blood flow
general anesthesia
cerebral collateral circulation
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2021-09-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Acute ischemic stroke due to large vessel occlusion is responsible of cerebral blood flow impairment with a progressive and extensive ischemic process. Cerebral collateral circulation may preserve an ischemic penumbra that could recover providing timely reperfusion of the occluded vessel. Mechanical thrombectomy is the standard of care for anterior circulation large vessel reperfusion. Strategy to promote cerebral blood flow in collateral circulation before reperfusion is scarce and rely mainly on blood pressure maintenance. Carbon dioxide is a potent cerebral vasodilator that could enhance collateral circulation blood flow and cerebral protection before reperfusion. General anesthesia with endotracheal mechanical ventilation could be used for thrombectomy and give the opportunity to modulate and control carbon dioxide tension in the blood. This study will test the effect of moderate hypercapnia on penumbral collateral circulation before reperfusion during mechanical thrombectomy for anterior circulation acute ischemic stroke under general anesthesia.

Detailed description: Study will compare 2 groups of patients treated for anterior circulation large vessel occlusion stroke thrombectomy under general anesthesia.

After anesthetic evaluation, patients will be randomized to receive moderate hypercapnia targeting an arterial CO2 tension (PaCO2) of 50mmHg or normocapnia targeting a PaCO2 of 40mmHg.

The anesthetic protocol will use:

* Rapid sequence induction for orotracheal intubation with PROPOFOL 2mg/Kg and SUXAMETHONIUM 1mg/Kg
* SUFENTANIL 0,1 µg/Kg and CISATRACURIUM 0,1mg/Kg
* Maintenance with intravenous continuous infusion of PROPOFOL targeting a BISpectral index 40 to 60
* Systolic blood pressure will have to be maintained +/- 10% of preoperative baseline value with limits between 120 and 185mmHg (with NOREPINEPHRINE as needed)
* Mechanical ventilation will use Tidal Volume of 7mL/Kg of ideal body weight, respiratory rate of 15/minute, End expiratory pressure of 5cmH2O. FiO2 will target SpO2 95-98%. Initial End Tidal CO2 (EtCO2) target will be 35mmHg.
* A first arterial blood gas analysis at groin puncture will evaluate CO2 alveolar-arterial gradient in order to obtain the expected PaCO2 in each group with respiratory rate modulation on the ventilator.
* ASITN baseline collaterality score will be evaluated at initial angiography with normocapnia in each group. A second evaluation of ASITN will be done just before deployment of intraarterial revascularisation device in hypercapnia or normocapnia depending on randomisation group.
* Targeted PaCO2 will have to be maintained using EtCO2 surrogate until the end of procedure.
* A second arterial blood gas analysis at the end of procedure will evaluate final PaCO2.

Eligibility criteria: Inclusion Criteria:

• Large vessel occlusion anterior circulation stroke (terminal carotid artery and/or middle cerebral artery M1-M2 segment) eligible to mechanical thrombectomy under general anesthesia

Exclusion Criteria :

* Active smoker
* Chronic respiratory failure with ambulatory oxygen supplementation
* Obesity with BMI\>40Kg/ m2
* Intubation before the procedure
* Heart failure with intolerance to decubitus
* Severe renal failure
* Suspected elevated intracranial pressure
* Pregnant or breastfeeding women

Primary outcomes:
measure: ASITN cerebral vascular collaterality score > 2
timeFrame: Before reperfusion of the occluded vessel
Secondary outcomes:
measure: ASITN cerebral vascular collaterality score
timeFrame: • At initial angiography in normocapnia and • Before reperfusion at randomized arterial CO2 tension level
measure: Volume of cerebral infarction
timeFrame: 24 hours after stroke
measure: Progression of cerebral infarction
timeFrame: 24 hours after stroke
measure: Neurological clinical outcome
timeFrame: 3 months
Other outcomes:
measure: Pial Vascular Collaterality within the symptomatic ischemic territory at admission
timeFrame: At admission
measure: Arterial carbon dioxide tension
timeFrame: At groin puncture and at the end of procedure
measure: Cerebral infarction extension
timeFrame: Before thrombectomy and at day 1
measure: Reperfusion assessed by mTICI
timeFrame: End of procedure
measure: Procedural delay
timeFrame: End of procedure
measure: Number of procedural anesthetic and radiological complications
timeFrame: End of procedure
measure: Number of Death and neurological complications
timeFrame: Day 7
Locations:
city: Clermont-Ferrand
country: France
facility: CHU
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Russell Chabanne, MD MSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: Schonenberger S, Henden PL, Simonsen CZ, Uhlmann L, Klose C, Pfaff JAR, Yoo AJ, Sorensen LH, Ringleb PA, Wick W, Kieser M, Mohlenbruch MA, Rasmussen M, Rentzos A, Bosel J. Association of General Anesthesia vs Procedural Sedation With Functional Outcome Among Patients With Acute Ischemic Stroke Undergoing Thrombectomy: A Systematic Review and Meta-analysis. JAMA. 2019 Oct 1;322(13):1283-1293. doi: 10.1001/jama.2019.11455.
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citation: Powers WJ, Rabinstein AA, Ackerson T, Adeoye OM, Bambakidis NC, Becker K, Biller J, Brown M, Demaerschalk BM, Hoh B, Jauch EC, Kidwell CS, Leslie-Mazwi TM, Ovbiagele B, Scott PA, Sheth KN, Southerland AM, Summers DV, Tirschwell DL; American Heart Association Stroke Council. 2018 Guidelines for the Early Management of Patients With Acute Ischemic Stroke: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2018 Mar;49(3):e46-e110. doi: 10.1161/STR.0000000000000158. Epub 2018 Jan 24.
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citation: Olsen TS, Larsen B, Herning M, Skriver EB, Lassen NA. Blood flow and vascular reactivity in collaterally perfused brain tissue. Evidence of an ischemic penumbra in patients with acute stroke. Stroke. 1983 May-Jun;14(3):332-41. doi: 10.1161/01.str.14.3.332.