Assessing Covert Consciousness During Dexmedetomidine and Ketamine Sedation: An fMRI Study

Phase 2Enrolling By InvitationNCT07705022

University of Michigan60 enrolled

Overview

This research is studying whether mental functions take place during different levels of anesthesia, using a commonly used drug (either dexmedetomidine \[with propofol in some participants\] or ketamine), which shows areas in the brain involved in thinking at different depths of anesthesia. As a result of this study, the researchers expect to gain a deeper understanding of mental function during different levels of anesthesia.

Dexmedetomidine is an FDA-approved sedative agent and is used off-label in this study for controlled experimental modulation of consciousness under direct anesthesiology supervision. Ketamine is a FDA-approved anesthetic and analgesic agent and is used off-label in this study for controlled experimental modulation of consciousness under direct anesthesiology supervision. Using fMRI and established cognitive paradigms, the proposed study will directly examine residual conscious processing under dexmedetomidine and ketamine and compare these findings with our existing propofol dataset from NCT03361605.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Enrollment

Conditions

Healthy Covert Consciousness

Interventions

Dexmedetomidine (+propofol as indicated)DRUG

Dexmedetomidine dosing will follow FDA-labeled parameters for procedural sedation, with a loading dose of 1 mcg/kg administered intravenously over 10 minutes, followed by maintenance infusion within the range of 0.2 to 1.0 mcg/kg/hr, titrated to clinical effect under anesthesiologist supervision. Sedation depth will be assessed behaviorally using standardized squeeze-response testing to determine lost responsiveness (LOR). If LOR is not achieved within labeled dexmedetomidine dosing limits, low-dose propofol will be conditionally added using a target-controlled infusion at an effect-site concentration of 0.5-1.5 μg/ml, which is below typical induction levels and intended to provide supplemental sedation while preserving spontaneous ventilation. Once LOR is achieved, sedation will be maintained within the approved dexmedetomidine range, with adjunct propofol continued only as clinically indicated.

KetamineDRUG

participants will first receive a subanesthetic ketamine infusion of 0.5 mg/kg administered intravenously over 40 minutes. After that, 1.5 mg/kg ketamine will be administered slowly as a bolus over 60 seconds. Based on prior experience with this paradigm, most subjects who lose responsiveness do so for approximately 10 minutes following the bolus dose. For a 70 kg healthy subject, the total ketamine dose in this paradigm is approximately 140 mg. This dosing remains within the range of standard anesthetic induction dosing, which is typically 1.5 to 2 mg/kg in clinical practice.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy study subjects with American Society of Anesthesiologists (ASA)-1 status * Right-handed * Body mass index (BMI) less than 30 * Participants will have the experience of playing tennis (or other racquet sport) at least 30 times in their lifetime * English speaking Exclusion Criteria: * Medical contraindication to MRI scanning; are unable to undergo MRI scanning because of possible pregnancy or currently breastfeeding * BMI greater than or equal to 30 * Metallic substances in the body * claustrophobia, anxiety, or cardiopulmonary disease; or have an intracranial structural abnormality on T1-weighted MRI scans * history of allergy to dexmedetomidine, ketamine, propofol, or any components of these medications, eggs or egg products, soybean or soybean products * neurological, cardiovascular, or pulmonary illness * significant head injury with loss of consciousness; learning disability or other developmental disorder * sleep apnea or any severe snoring history * gastroesophageal reflux disease (GERD) or heartburn; pancreatitis or a history of pancreatitis, * sensory/motor loss sufficient to interfere with performance of the study * epilepsy/seizure disorder (including a history of seizures) or stroke (including a history of stroke). * history of schizophrenia spectrum disorder, bipolar disorder, other psychotic disorder, or any prior adverse psychiatric reaction to ketamine or similar drugs * Participants taking medications that, in the judgment of the investigators or attending anesthesiologist, may interact with the study drugs or increase the risk of participation will also be excluded * participants with hypertension or diabetes mellitus * tattoos in the head or neck region will be excluded from study; other tattoos are subject to determination by investigators based on their assessment regarding participant safety * recent food or liquid intake (within 8 hours) * history of drug use, have a positive drug screen, are unwilling to abstain from alcohol for 24 hours prior to dosing, or have a current history of nicotine use. * Potential participants who have participated in a clinical trial using an investigational drug or device within 30 days will be considered for enrollment after 30 days. * History of a difficult airway with a previous anesthetic

Locations (1)

University of Michigan

Ann Arbor, Michigan, United States

Outcomes

Primary Outcomes

Blood Oxygen Level Dependent (BOLD) response to mental imagery tasks

Three mental imagery tasks will be used: tennis imagery, navigation imagery, and hand-squeeze imagery

Time frame: Up to approximately 130 minutes

Secondary Outcomes

Grip force (in mmHg) of participants' hand squeezing on a rubber ball in response to squeeze instructions

Time frame: Up to approximately 130 minutes

Data from ClinicalTrials.gov

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