CO2 Modulation in Endovascular Thrombectomy for Acute Ischemic Stroke

Phase 2

Recruiting

• Conditions: Carbon Dioxide; Thrombectomy; Anesthesia, General; Cerebrovascular Circulation; Ischemic Stroke, Acute
• Interventions: Biological: NORMOCAPNIA; Biological: HYPERCAPNIA

• Registration Number: NCT05051397
• Lead Sponsor: University Hospital, Clermont-Ferrand

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.

Study Timeline

• Study First Submitted: 2021-07-09
• Study First Submitted QC: 2021-09-10
• Study First Posted: 2021-09-21
• Study Start: 2022-07-20
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-21
• Last Update Posted: 2022-12-22
• Primary Completion: 2024-06-19
• Study Completion: 2024-10-19

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
NORMOCAPNIA	NORMOCAPNIA	Under general anesthesia with mechanical ventilation, PaCO2=40mmHg will be targeted
HYPERCAPNIA	HYPERCAPNIA	Under general anesthesia with mechanical ventilation, PaCO2=50mmHg will be targeted

Primary Outcome Measures

Name	Time	Method
ASITN cerebral vascular collaterality score > 2	Before reperfusion of the occluded vessel	American Society of Interventional and Therapeutic Neuroradiology (ASITN) cerebral vascular collaterality score ranges from 0 (no collaterals visible to the ischemic site) to 4 (complete and rapid collateral blood flow to the vascular bed in the entire ischemic territory by retrograde perfusion). A score \> 2 indicate at least collaterals with slow but complete angiographic blood flow of the ischemic bed by the late venous phase.

Secondary Outcome Measures

Name	Time	Method
ASITN cerebral vascular collaterality score	• At initial angiography in normocapnia and • Before reperfusion at randomized arterial CO2 tension level	American Society of Interventional and Therapeutic Neuroradiology (ASITN) variation during the procedure
Volume of cerebral infarction	24 hours after stroke	Evaluated with Magnetic Resonance Imaging in milliliters
Neurological clinical outcome	3 months	Ordinal and dichotomized modified rankin scale (mRS) ranging from 0 (no disability) to 6 (death); good outcome will be defined as mRS 0-2.
Progression of cerebral infarction	24 hours after stroke	Evaluated with Magnetic Resonance Imaging or Computed Tomography in milliliters depending on type of radiological modality for patient selection

Trial Locations

Locations (1)

CHU; 🇫🇷 Clermont-Ferrand, France