Non-Invasive Cerebral Autoregulation Monitoring Validation and Autonomic Modulation in Aneurysmal Subarachnoid Hemorrhage: A Two-Component Prospective Study of EVD Clamping Validation, CA Natural History, and the Effects of Cervical Sympathetic Block and Transcutaneous Auricular Vagal Nerve Stimulation on Cerebral Autoregulation Parameters
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 300
- Locations
- 1
Study Overview
Brief Summary
This is a two-component prospective study of adult aneurysmal subarachnoid hemorrhage (aSAH) patients admitted to the Neurosciences Intensive Care Unit (NSICU) at UT Southwestern Medical Center. Component 1 (active upon IRB approval) validates Brain4Care (B4C) extensometry-derived noninvasive cerebral autoregulation (CA) indices against invasive ICP-derived equivalents in aSAH patients with open external ventricular drains (EVDs), and characterizes the prospective natural history of multi-modal CA parameter evolution through the delayed cerebral ischemia (DCI) window (admission through Day 14). Component 2 (activated upon PI readiness declaration) assesses the within-subject effect of cervical sympathetic block (CSB) and transcutaneous auricular vagal nerve stimulation (taVNS) on CA parameters in enrolled aSAH patients.
Detailed Description
BACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) affects approximately 35,000 Americans annually and carries a 30-day mortality of approximately 40%. Delayed cerebral ischemia (DCI) - caused by vasospasm, microvascular dysfunction, and impaired cerebrovascular regulation - complicates 25-35% of survivors during the 4-14 day post-rupture window. Cerebral autoregulation (CA) impairment predicts DCI onset and poor neurological outcome. Standard ICP-based CA indices cannot be computed through an open EVD - present in approximately 50-75% of aSAH patients - because the transducer is exposed to ambient pressure. This technical barrier has precluded CA-guided management in the most common clinical aSAH scenario for over two decades.
The autonomic nervous system is a central, understudied regulator of CA in aSAH. Aneurysm rupture produces a massive catecholamine surge coinciding with the early window of CA impairment. We hypothesize that sympathetically-mediated cerebrovascular vasoconstriction contributes to CA failure, and that restoration of sympathovagal balance can shift CA parameters toward a more protective state.
TWO-COMPONENT DESIGN:
COMPONENT 1 - Validation and Natural History (activates immediately upon IRB approval):
A standardized 15-minute EVD clamping protocol (5-minute equilibration plus 10-minute simultaneous invasive/noninvasive CA recording; ICP abort threshold greater than 20 mmHg sustained for 5 or more minutes) is used to validate B4C-derived CA indices (nPRx, nCPPopt, nMx) against invasive ICP-derived equivalents by Bland-Altman analysis and intraclass correlation. NIRS-based MAPopt (TOxA, COx) is characterized as an EVD-independent CA metric. Longitudinal multi-modal CA monitoring proceeds through ICU Day 14 for all enrolled participants.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Basic Science
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •(Component 1 - All Enrolled Participants):
- •Age 18 years or older
- •Primary diagnosis of aneurysmal subarachnoid hemorrhage (aSAH), confirmed by imaging
- •Admitted to the NSICU at Clements University Hospital, UT Southwestern Medical Center
- •Informed consent obtained from subject or legally authorized representative (as defined under Texas Health and Safety Code Section 166.039)
- •Brain4Care extensometry sensor placeable at an appropriate cranial site not occluded by surgical dressings or EVD hardware
- •Open EVD with active continuous ICP monitoring (required for EVD clamping sub-protocol only; not required for Aims 2 or 3)
Exclusion Criteria
- •(Component 1):
- •Age younger than 18 years
- •Prisoner status
- •Primary NSICU admission diagnosis other than aSAH
- •Active declination by subject or legally authorized representative
- •Brain4Care sensor not placeable at any accessible cranial site
- •Active clinical deterioration making research monitoring impractical at time of approach
- •Physician-of-record declining research enrollment for clinical reasons
- •Inability to provide informed consent in English
- •Known pregnancy at time of enrollment
- •Additional Inclusion Criteria for Component 2 (Aim 3 - CSB and taVNS):
- •At least one successful EVD clamping session completed
- •PI documentation of Component 2 operational readiness, co-signed by qualified co-investigator or Department Director
- •INR 1.5 or less and platelet count 50,000/uL or greater within 24 hours prior to each CSB procedure
- •No active infection or cellulitis at right anterolateral neck
- •No known allergy to ropivacaine or amide local anesthetics
- •No contralateral phrenic nerve palsy or severe pre-existing respiratory compromise
- •No cardiac pacemaker or implanted cardiac device contraindicating taVNS
- •No allergy to electrode adhesive materials
- •Continuous cardiac telemetry active and interpretable
- •Resting HR 60 bpm or greater on two readings within 24 hours prior to session
- •No current use of Class I or III antiarrhythmic medications
- •No clinically significant AV conduction abnormality
- •Additional Exclusion Criteria for Component 2:
- •Prior ipsilateral right-sided cervical surgery, radiation, or known anatomical distortion precluding safe C6 approach
- •Hemodynamic instability with active vasopressor escalation at time of planned CSB
- •Active uncontrolled tachyarrhythmia or bradyarrhythmia at time of taVNS session
- •Physician-of-record declining autonomic modulation procedures for any clinical reason
- •Known or suspected pregnancy
Investigators
Noah Jouett
Principal Investigator, Department of Anesthesiology and Pain Management
University of Texas Southwestern Medical Center