Neurocognitive Dysfunction
Conditions
Keywords
neurocognitive function, neural inertia, xenon gas
Brief summary
The dual objectives of this study are to determine if the phenomenon of neural inertia is present in humans and to determine whether the order of neurocognitive function is invariant among anesthetic agents. This study will enroll 24 healthy volunteers, ages 20-40 years, who will receive xenon gas (concentrations ranging from 0% to 60%) delivered via inhaled route through the ENHANCER 3000.
Detailed description
This is a multimodal, nonrandomized study of healthy subjects. After meeting enrollment criteria, subjects will receive a baseline neurocognitive testing on a computer for 15 minutes and will then receive a wrist watch actigraphy device to record their rest/activity patterns over 8-14 days. On the study day (roughly two weeks later), repeat baseline neurocognitive testing will be performed after subjects are fitted with a high density EEG head cap. The actual intervention (delivery of inhaled xenon gas in stepwise increasing followed by decreasing doses) should occur over 2 hours along with verbal tests to assess the presence/absence of consciousness at each xenon concentration. Xenon doses have been chosen specifically to evaluate the point at which individuals lose and then regain consciousness. Doses are escalated up through those used in human anesthesiology (75%) that permit surgery. After exposure, serial neurocognitive testing will occur every 30 minutes for 3 hours post emergence. Subjects are discharged from the study's intervention day to home only upon reaching standard post-anesthesia care unit criteria (modified Aldrete score ≥9). A post-procedure follow up phone call will occur within 24 hours of anesthetic exposure to ensure that the subject remains well. The individual's involvement is completed upon returning the Actigraphy watch 1 week after the exposure day. The expected duration of subject participation is up to 3 weeks.
Interventions
DRUGXenon
drug given in concentrations of 0% to 60% over period of 2 hours
Sponsors
University of Pennsylvania
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy volunteers ages 20-40 years old * American Society of Anesthesiologists (ASA) Physical Status I or II (i.e. healthy) * Body Mass Index \<30 kg/m2 * Easily visible uvula
Exclusion criteria
* Any physical signs that would suggest a difficult airway (e.g. mouth opening \<3cm, short distance between the chin and neck, poor mandibular subluxation, thick neck) * History of reactive airway disease * Current or history of neuropsychiatric disorders * History or current use of psychotropic medications, * History or current obstructive sleep apnea * Current or history of cardiovascular disease or arrhythmias, * Current or history of chronic sleep disorders * History of postoperative nausea/vomiting * Family history of problems with anesthesia (including but not limited to malignant hyperthermia), * Current or history of Motion sickness * Current tobacco use * Current pregnancy or currently breastfeeding * Positive urine toxicology screen * History of seizure disorder, head injury, or brain tumor * Alcohol consumption greater than 12 drinks per week or more than 4 drinks on any single day * Inability to provide informed consent * Inability to achieve mask seal on intervention day
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Xenon Concentrations at Which Consciousness is Lost and Regained | 4 hours | To determine in healthy human volunteers if the brain concentrations of xenon (as determined by CT imaging) are identical at the point of loss and return of consciousness. If the values are significantly different, then we conclude that there is evidence for hysteresis in circuits regulating arousal. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Neurocognitive Recovery Upon Emergence From Xenon as Measured by Neurocognitive Battery Testing | 4 hours | To determine if the order of neurocognitive recovery upon emergence from xenon general anesthesia is sequential or simultaneous and if the former is true to determine if the pattern is identical to that of isoflurane (as measured in a previously completed study (PMID: 33970101). |
| Effects of Xenon on Gross Rest / Activity as Measured Using Wristwatch Actigraphy | 1 week prior to xenon exposure and 1 week post xenon exposure | To determine if transient exposure to xenon anesthesia induces a change in rest-activity rhythms (as measured from actigraphy) as has been previously reported for isoflurane. The plan was to collect wrist actigraphy for 1 week before the xenon exposure day and for 1 week following the xenon exposure day. Wrist actigraphy data would be fit with a cosinar analysis function (see Fig 5 from our previous work, PMID: 33970101). |
| Effects of Xenon on Brain Electrical Activity as Measured by EEG Delta Power | 4 hours | EEG delta power was modeled as a function of estimated brain xenon concentration using nonlinear sigmoidal dose-response curves. Two models were evaluated: 1. a single curve fit to combined induction (increasing xenon concentration) and emergence (decreasing xenon concentration) data, and 2. separate curves fit to induction and emergence phases. Model fit was compared using Akaike Information Criterion (AIC) to assess whether a single (model 1) or phase-specific relationship (model 2) best described the data. Smaller Akaike Information Criterion values indicate a more likely model fit. Typically AIC differences greater than 4 are considered significant. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORMaz B Kelz, MD, PhD
University of Pennsylvania
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants |
| Age, Continuous | 24.0 years |
| Race/Ethnicity, Customized Asian | 2 Participants |
| Race/Ethnicity, Customized Black or African American | 4 Participants |
| Race/Ethnicity, Customized Hispanic | 5 Participants |
| Race/Ethnicity, Customized Other/No Response | 3 Participants |
| Race/Ethnicity, Customized White | 15 Participants |
| Region of Enrollment United States | 29 participants |
| Sex: Female, Male Completing study Female | 8 Participants |
| Sex: Female, Male Completing study Male | 5 Participants |
| Sex: Female, Male Enrolled Female | 12 Participants |
| Sex: Female, Male Enrolled Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 29 |
| other Total, other adverse events | 0 / 29 |
| serious Total, serious adverse events | 0 / 29 |
Outcome results
None listed