CO2 Modulation in Endovascular Thrombectomy for Acute Ischemic Stroke

Overview

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.

Full Title of Study: “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

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Double (Participant, Outcomes Assessor)
  • Study Primary Completion Date: August 2, 2023

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.

Interventions

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

Arms, Groups and Cohorts

  • Experimental: HYPERCAPNIA
    • Under general anesthesia with mechanical ventilation, PaCO2=50mmHg will be targeted
  • Active Comparator: NORMOCAPNIA
    • Under general anesthesia with mechanical ventilation, PaCO2=40mmHg will be targeted

Clinical Trial Outcome Measures

Primary Measures

  • ASITN cerebral vascular collaterality score > 2
    • Time Frame: 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 Measures

  • ASITN cerebral vascular collaterality score
    • Time Frame: • 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
    • Time Frame: 24 hours after stroke
    • Evaluated with Magnetic Resonance Imaging in milliliters
  • Progression of cerebral infarction
    • Time Frame: 24 hours after stroke
    • Evaluated with Magnetic Resonance Imaging or Computed Tomography in milliliters depending on type of radiological modality for patient selection
  • Neurological clinical outcome
    • Time Frame: 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.

Participating in This Clinical Trial

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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • University Hospital, Clermont-Ferrand
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Russell Chabanne, MD MSc, Principal Investigator, University Hospital, Clermont-Ferrand
  • Overall Contact(s)
    • Lise Laclautre, +33 4 73 754963, promo_interne_drci@chu-clermontferrand.fr

References

Schönenberger S, Hendén PL, Simonsen CZ, Uhlmann L, Klose C, Pfaff JAR, Yoo AJ, Sørensen LH, Ringleb PA, Wick W, Kieser M, Möhlenbruch MA, Rasmussen M, Rentzos A, Bösel 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.

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. Review.

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. Review. Erratum in: Stroke. 2018 Mar;49(3):e138. Stroke. 2018 Apr 18;:.

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.

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.

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