CO2 Modulation in Endovascular Thrombectomy for Acute Ischemic Stroke

Anesthesia, General Clinical Trial

— COMET-AIS  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05051397
• Other study ID #: COMET-AIS (AOI 2020 Chabanne)
• Secondary ID: AOI...
• Status: Recruiting
• Phase: Phase 2
• Start date: July 20, 2022
• Est. completion date: October 19, 2024

Study information

• Verified date: December 2022
• Source: University Hospital, Clermont-Ferrand
• Contact: Lise Laclautre
• Phone: +33 4 73 754963
• Email: promo_interne_drci[@]chu-clermontferrand.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: October 19, 2024
• Est. primary completion date: June 19, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Anesthesia, General
• Carbon Dioxide
• Cerebral Infarction
• Cerebrovascular Circulation
• Ischemia
• Ischemic Stroke
• Stroke
• Thrombectomy

Intervention

Biological:
• HYPERCAPNIA
Controlled moderate hypercapnia PaCO2 50mmHg under general anesthesia with mechanical ventilation
• NORMOCAPNIA
Controlled normocapnia PaCO2 40mmHg under general anesthesia with mechanical ventilation

Locations

Country	Name	City	State
France	CHU	Clermont-Ferrand

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Clermont-Ferrand

Country where clinical trial is conducted

France, 

References & Publications (5)

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. — View 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. Erratum In: Stroke. 2018 Mar;49(3):e138. Stroke. 2018 Apr 18;: — View 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. Erratum In: JAMA. 2019 Dec 24;322(24):2445. — View Citation

Slupe AM, Kirsch JR. Effects of anesthesia on cerebral blood flow, metabolism, and neuroprotection. J Cereb Blood Flow Metab. 2018 Dec;38(12):2192-2208. doi: 10.1177/0271678X18789273. Epub 2018 Jul 16. — View Citation

Willie CK, Macleod DB, Shaw AD, Smith KJ, Tzeng YC, Eves ND, Ikeda K, Graham J, Lewis NC, Day TA, Ainslie PN. Regional brain blood flow in man during acute changes in arterial blood gases. J Physiol. 2012 Jul 15;590(14):3261-75. doi: 10.1113/jphysiol.2012.228551. Epub 2012 Apr 10. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Pial Vascular Collaterality within the symptomatic ischemic territory at admission	Pial Vascular collaterality evaluated at admission with CT or MRI during patient selection for thrombectomy using the Pial Arterial Filling Score (from 0 indicated no collaterality to 5 indicating excellent collaterality)	At admission
Other	Arterial carbon dioxide tension	Arterial carbon dioxide tension will be measured at 2 time points.	At groin puncture and at the end of procedure
Other	Cerebral infarction extension	The Alberta Stroke Program Early Computed Tomography Score (ASPECTS) is an imaging measure of the extent of ischemic stroke. Scores range from 0 to 10, with higher scores indicating a smaller infarct core.	Before thrombectomy and at day 1
Other	Reperfusion assessed by mTICI	The modified Treatment In Cerebral Ischemia (mTICI) reperfusion scale ranging from 0 (no perfusion) to 3 (full perfusion with filling of all distal Branches). Good reperfusion will be defined as a score of 2B-3.	End of procedure
Other	Procedural delay	Time frame from angiosuite admission to groin puncture to reperfusion if any	End of procedure
Other	Number of procedural anesthetic and radiological complications	Procedural Safety outcomes	End of procedure
Other	Number of Death and neurological complications	Safety outcomes	Day 7
Primary	ASITN cerebral vascular collaterality score > 2	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.	Before reperfusion of the occluded vessel
Secondary	ASITN cerebral vascular collaterality score	American Society of Interventional and Therapeutic Neuroradiology (ASITN) variation during the procedure	• At initial angiography in normocapnia and • Before reperfusion at randomized arterial CO2 tension level
Secondary	Volume of cerebral infarction	Evaluated with Magnetic Resonance Imaging in milliliters	24 hours after stroke
Secondary	Progression of cerebral infarction	Evaluated with Magnetic Resonance Imaging or Computed Tomography in milliliters depending on type of radiological modality for patient selection	24 hours after stroke
Secondary	Neurological clinical outcome	Ordinal and dichotomized modified rankin scale (mRS) ranging from 0 (no disability) to 6 (death); good outcome will be defined as mRS 0-2.	3 months