Acute Medical Conditions, Acute Neurological Injury
Conditions
Keywords
vagal nerve stimulation, pathologic process, acute medical condition, brain diseases, central nervous system diseases, spine cord injury, vascular diseases, hemorrhage, acute neurological condition
Brief summary
This study will demonstrate the impact of taVNS on reducing adverse events in NeuroICU patients, determine if taVNS reduces length of stay, and quantify the economic benefits of taVNS implementation in a broader neurocritical care population.
Detailed description
Vagal nerve stimulation (VNS) has been studied as a novel method of reducing inflammation, and it has been successfully used in animal models of inflammatory conditions. The purpose of the proposed study is to determine if transcutaneous auricular VNS will impact 1) the occurrence of hospital-acquired infections, 2) the need for tracheostomy due to prolonged intubation, 3) the effect on hospital-stay physiology (e.g., vital signs and blood glucose metrics), and 4) inflammatory markers in the blood, and 5) the health economics. This study will involve randomizing patients to stimulation with VNS, or sham stimulation. Blood samples for inflammatory marker analysis will be collected upon admission and serially throughout the patient's admission. Clinical events tracked during the hospital stay include the occurrence of hospital-acquired infections, tracheostomy, changes in vital signs and blood glucose, development of peri-hematomal edema, and interventions for edema (medical or surgical). Outcomes following admission will include intensive care unit and hospital stay, cost analysis of hospital stay, discharge destination, functional scores at discharge, and at follow-up visits for up to 1 year after discharge. No additional appointments will be made specially for the research study.
Interventions
Transcutaneous auricular vagal nerve stimulation
Transcutaneous auricular vagal nerve ear clip applied without current/stimulation
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
All participants will be fitted with an auricular stimulator, but blinded to whether they are receiving stimulation or not. Outcome scores and measures will be assessed and recorded by clinicians and research team members blinded to the treatment arm.
Intervention model description
Participants are assigned to either stimulation or sham stimulation arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥18 * Admission to the NeuroICU within 36 hours of onset of an acute medical condition. * Patient or authorized legal representative should be able to provide consent within 36 hours of ICU arrival * Presence of at least one predictor of critical illness and/or severe brain / spinal cord injury: * Glasgow Coma Scale GCS \>3 & \<= 12 at admission * NIH stroke scale of 6 or greater * Requirement for ongoing mechanical ventilation * Requirement for ongoing vasopressor support * Diagnosis of subarachnoid hemorrhage * Diagnosis of intracerebral hemorrhage with hematoma volume \> 5 ml * Diagnosis of moderate-severe traumatic brain injury (GCS \>3 & \<= 12) * Refractory Status epilepticus requiring continuous sedative infusions
Exclusion criteria
* Systemic immunosuppression * Receiving ongoing cancer therapy * Implanted electrical device (e.g., pacemaker, stimulator) * Bradycardia on admission (Sustained bradycardia on arrival with a heart rate \< 50 bpm for \>5 minutes) * Risk of imminent death or limitation of care (e.g., Glasgow Coma Scale of 3, pupillary dilatation) * Expected ICU stay of less than 72 hours, as determined by attending physician or ICU fellow * Pregnancy * COVID-19
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cost of Hospital Admission | Through hospital admission, average 14 days | Evaluation of total hospital admission cost of stay ($) |
| Occurrence of hospital-acquired infections | 14 days | Data will be collected from medical records. Infections will include ventilator-associated pneumonia, catheter-associated urinary tract infections, bloodstream infection, clostridium difficile, and ventriculitis. |
| Changes in heart rate/heart trace | 14 days | Evaluation of changes in centrally monitored heart rate/heart trace to calculate heart rate variability and QT interval. |
| Blood glucose measurement | 14 days | Daily evaluation of blood glucose (mg/dL) |
| Insulin requirement | 14 days | Assessment of daily insulin requirement (Units) |
| Hospital length of stay | Through hospital admission, average 14 days | Total length of stay in the hospital, and in the intensive care unit |
| Neurological outcome | 1 year | Modified Rankin Scale for Neurological Disability (minimum score 0, maximum score 6, better outcomes have lower scores) |
| Discharge destination | After hospital discharge, on average 14 days after admission. | Patient discharge destination (ie, home, acute rehab) |
| Cost of ICU stay | Through hospital admission, average 14 days | Evaluation of total ICU cost of stay ($) |
| Assessment of the need for tracheostomy. | 14 days | Quantification of patients who need tracheostomy due to prolonged intubation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in inflammatory markers in cerebrospinal fluid | 14 days | rebrospinal fluid samples collected on days 1, 4, 7, 10, and 14 to evaluate for TNF-α, IL-6, IL-10, and IFN-γ . Inflammatory markers will be reported in pg/mL. |
| Cerebral Edema | 14 days | Assessment of cerebral edema on each medically indicated and obtained head CT scan through assessment of selective sulcal volume (SSV) |
| Neurological outcome at discharge and first follow-up | up to 1 year. | Disease-specific neurological outcome metric at discharge and first follow-up. Glasgow Coma Scale (GCS, maximum score: 15; minimum score: 3; better outcomes have higher scores). |
| Neurological Outcome at discharge and first follow-up | up to 1 year. | Disease-specific neurological outcome metric at discharge and first follow-up. Glasgow Outcome Scale-Extended (GOSE, maximum score: 8; minimum score 1; better outcomes have higher scores). |
| Neurological Outcome at discharge and first follow-up. | Up to 1 year. | Disease-specific neurological outcome metric at discharge and first follow-up. National Institutes of Health Stroke Scale (NIHSS, maximum score: 42; minimum score: 1; better outcomes have lower scores). |
| Diagnosis of hospital-acquired infections | Through hospital admission, average 14 days | Binary assessment of hospital-acquired infections (ventilator-associated pneumonia, catheter associated urinary tract infection, Clostridium difficile infection, ventriculitis) diagnosis acquired from hospital databases. (Yes or No rating, better outcomes associated with No). |
| Use of a ventilator | Through hospital admission, average 14 days | Quantification of days on ventilator |
| Change in the inflammatory markers TNF-α, IL-6, IL-10, and IFN-γ in plasma | 14 days | Blood samples collected on days 1, 4, 7, 10, and 14 (Day 1 serves as baseline, prior to first treatment). Inflammatory markers will be reported in pg/mL. |
Countries
United States
Contacts
Primary ContactRaj Dhar, MD
Backup ContactAnna Huguenard, MD
Outcome results
None listed