Brain Injuries, Traumatic, Cerebral Hemorrhage, Delayed Emergence From Anesthesia, Encephalopathy, Ischemic Stroke, Subarachnoid Hemorrhage, Aneurysmal
Conditions
Keywords
aneurysmal subarachnoid hemorrhage, delayed cerebral ischemia, cerebral autoregulation, CPPopt, MAPopt, Brain4Care, SedLine, quantitative EEG, near-infrared spectroscopy, COx, TOxA, transcranial Doppler, neurocritical care, NSICU, noninvasive intracranial monitoring, Moberg Clinical Platform, multimodal neuromonitoring
Brief summary
This is a prospective observational cohort study of adult patients admitted to the Neurosciences Intensive Care Unit (NSICU) at UT Southwestern Medical Center. The study acquires multimodal neuromonitoring data - including SedLine quantitative EEG (qEEG) from standard-of-care monitoring, Brain4Care (B4C) noninvasive intracranial dynamics monitoring, and near-infrared spectroscopy (NIRS)-derived cerebral autoregulation (CA) indices where NIRS is already in clinical use - and links these data to bedside physiologic, medication, diagnostic, and clinical outcome variables during standard care. No alteration of clinical management occurs. The study prioritizes aneurysmal subarachnoid hemorrhage (aSAH) patients to characterize the natural history of noninvasive CA parameter evolution through the delayed cerebral ischemia (DCI) window (admission through Day 14) and provides preliminary data for subsequent interventional study design.
Detailed description
BACKGROUND: Patients admitted to the NSICU undergo rapid physiologic changes related to primary neurologic injury, secondary brain injury, sedation, mechanical ventilation, and evolving systemic illness. Cerebral autoregulation (CA) - the brain's intrinsic mechanism for maintaining stable perfusion across a range of systemic arterial pressures - is measurably impaired in aSAH, traumatic brain injury (TBI), intracerebral hemorrhage (ICH), and acute ischemic stroke. In aSAH, CA impairment during the 4-14 day post-rupture window is independently associated with delayed cerebral ischemia (DCI), the leading cause of preventable death and disability in survivors. Approximately 75% of aSAH patients require an external ventricular drain (EVD), which prevents standard ICP-based CA monitoring. B4C extensometry and NIRS-derived CA indices offer EVD-independent monitoring approaches whose feasibility and signal characteristics in aSAH have not been prospectively described. DESIGN: Single-center prospective observational cohort study at the UT Southwestern NSICU. Eligible subjects may undergo B4C extensometry monitoring (the sole research-specific device under this protocol) and/or have research data recorded from existing standard-of-care clinical monitoring including SedLine qEEG, full-montage long-term monitoring EEG (where clinically ordered), NIRS, invasive ICP/CPP from EVD monitors, transcranial Doppler (TCD; standard of care for aSAH at UT Southwestern), and NeurOptics NPi automated pupillometry. The Moberg Clinical Platform (Moberg Analytics; FDA-cleared) serves as the primary data acquisition hub in the NSICU, aggregating synchronized high-resolution physiologic waveforms from existing bedside monitors without placing any additional research devices. MONITORING MODALITIES: Research device placed specifically for research purposes under this protocol: \- Brain4Care (B4C) extensometry: skull-mounted noninvasive sensor recording cranial compliance-related waveform morphology (P2/P1 ratio, Time to Peak), from which surrogate CA indices (nPRx, nCPPopt, nMx) are derived. Standard-of-care clinical data recorded for research purposes (no additional devices placed): * SedLine qEEG: clinically placed forehead sensor used for sedation monitoring as standard of care; provides Patient State Index, Spectral Edge Frequency, and raw EDF waveforms. * Full-montage long-term monitoring EEG: from clinically ordered continuous EEG electrodes for seizure and ADR monitoring where applicable. * NIRS (near-infrared spectroscopy): regional cerebral oxygenation; CA indices computed include cerebral oximetry index (COx) and total oxygenation reactivity index (TOxA). * Clinical ICP/CPP waveform data from EVD transducer where present. * TCD vasospasm surveillance (daily studies as standard of care for aSAH; peak and mean velocities, Lindegaard ratio). * NeurOptics NPi pupillometry: NPi, constriction velocity, latency, amplitude. * Moberg Clinical Platform: synchronized arterial blood pressure, ICP, ECG/HRV, SpO2, EtCO2, CVP, ventilator parameters, NIRS. ASAH PRIORITY ENROLLMENT: For aSAH patients, the protocol prioritizes monitoring through ICU Day 14 to characterize the natural history of B4C-derived and NIRS-derived CA index evolution through the DCI window. An optional 90-day follow-up captures functional and neurological outcomes beyond hospital discharge. DATA MANAGEMENT: Subjects are assigned unique study identifiers. Direct identifiers are removed from analytic datasets. De-identified data may be shared with qualified external collaborators under executed data use agreements and with applicable IRB approval. De-identified data from this study may be combined with data from the companion NSICU Autonomic Modulation Study for analyses within the approved scope of both protocols.
Interventions
None listed
Sponsors
University of Texas Southwestern Medical Center
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 18 years or older * Admitted to the NSICU at UT Southwestern Medical Center * Informed consent obtained from subject or legally authorized representative (as defined under Texas Health and Safety Code Section 166.039), or consent process underway per institutional policy * At least one study monitoring modality feasible (SedLine qEEG and/or Brain4Care extensometry); NIRS data collected where already in standard clinical use
Exclusion criteria
* Age younger than 18 years * Prisoner status * Active declination of participation by subject or legally authorized representative * Absence of both subject and legally authorized representative consent when required * Clinical condition preventing safe placement of any study monitor (e.g., extensive facial or scalp injury, surgical dressings or hardware at all possible sensor sites, open wounds at sensor locations, severe uncontrolled agitation) * Anticipated clinical data capture insufficient for meaningful analysis * Urgent clinical priorities making research monitor placement inappropriate at time of approach * Inability to provide informed consent in English; study consent materials are available in English only
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of enrolled participants with analyzable Brain4Care extensometry (P2/P1 ratio) recording across NSICU diagnoses | Through ICU Day 14 or hospital discharge, whichever occurs first | Percentage of enrolled participants with at least one successful Brain4Care (B4C) extensometry monitoring session yielding analyzable P2/P1 ratio data. Signal quality assessed by artifact burden and adequate waveform morphology. Reported as a single proportion compared across primary NSICU diagnostic groups (aSAH, TBI, ICH, stroke, other). |
| Proportion of Brain4Care extensometry sessions with computable cerebral autoregulation indices (nPRx) across NSICU diagnoses | Through ICU Day 14 or hospital discharge, whichever occurs first | Percentage of Brain4Care (B4C) extensometry monitoring sessions from which the noninvasive pressure reactivity index (nPRx) can be computed from B4C waveforms and concurrent arterial blood pressure data. Reported as a single proportion compared across primary NSICU diagnostic groups (aSAH, TBI, ICH, stroke, other). |
| NIRS-derived cerebral oximetry index (COx) trajectory through the delayed cerebral ischemia window in aSAH | ICU admission through Day 14 post-rupture | Prospective characterization of near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx; unitless, range -1 to +1) trajectory from NSICU admission through Day 14 in aSAH patients. Correlation of COx trajectory with DCI onset (clinical and imaging-confirmed) and neurological outcome at discharge, reported as Spearman correlation coefficients. |
| NIRS-derived optimal mean arterial pressure (MAPopt) trajectory through the delayed cerebral ischemia window in aSAH | ICU admission through Day 14 post-rupture | Prospective characterization of near-infrared spectroscopy (NIRS)-derived optimal mean arterial pressure (MAPopt; reported in mmHg) trajectory from NSICU admission through Day 14 in aSAH patients. Correlation of MAPopt trajectory with DCI onset (clinical and imaging-confirmed) and neurological outcome at discharge, reported as Spearman correlation coefficients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| SedLine Patient State Index values in relation to sedation exposure and clinical neurological status | Duration of ICU stay (expected 7-21 days for aSAH; varies by diagnosis) | Characterization of SedLine-derived Patient State Index (PSI; unitless, range 0-100) in relation to sedative medication exposure, clinical neurological status, primary NSICU diagnosis, and neurological outcome at discharge. PSI values reported as median with interquartile range stratified by sedation state and diagnostic group. |
| SedLine Spectral Edge Frequency values in relation to sedation exposure and clinical neurological status | Duration of ICU stay (expected 7-21 days for aSAH; varies by diagnosis) | Characterization of SedLine-derived Spectral Edge Frequency (SEF95; reported in Hz) in relation to sedative medication exposure, clinical neurological status, primary NSICU diagnosis, and neurological outcome at discharge. SEF95 values reported as median with interquartile range stratified by sedation state and diagnostic group. |
| Proportion of Brain4Care extensometry monitoring sessions successfully completed across NSICU clinical care states | Through ICU Day 14 or hospital discharge | Percentage of Brain4Care (B4C) extensometry monitoring sessions successfully completed, reported as a single proportion stratified by clinical care state (intubated/ventilated vs. extubated; sedated vs. awake; EVD present vs. absent). Duration of analyzable monitoring epochs reported in hours. Proportion of patients with multi-session longitudinal data reported as percentage. |
| Correlation between transcranial Doppler (TCD) mean flow velocity and Brain4Care-derived noninvasive pressure reactivity index (nPRx) in aSAH | ICU Day 1 through Day 14 | Spearman correlation coefficient between daily transcranial Doppler (TCD)-derived mean flow velocity (cm/s) and concurrently computed Brain4Care (B4C)-derived noninvasive pressure reactivity index (nPRx) in aSAH patients. Temporal association between TCD-defined vasospasm severity (Lindegaard ratio) and nPRx deterioration characterized as time-lagged cross-correlation. |
| Functional status at 90 days post-discharge assessed by modified Rankin Scale via medical record review | 90 days post-hospital discharge | Functional and neurological status assessed by modified Rankin Scale (mRS) score via medical record review and/or optional structured contact at 90 days. Reported as ordinal mRS score (0-6). This component is not required for protocol completion; omission does not constitute a protocol deviation. |
Countries
United States
Contacts
CONTACTNoah Jouett, DO, PhD
PRINCIPAL_INVESTIGATORNoah Jouett, DO, PhD
University of Texas Southwestern Medical Center
Outcome results
None listed