Anesthesia
Conditions
Brief summary
We are doing this research study to find out how and where ketamine acts in the brain. Ketamine is an anesthetic (a drug or agent used to decrease or eliminate the feeling of pain by putting you in an unconscious state). We will look at the brain using a machine that records the brain's electrical activity, called an electroencephalogram (EEG). We will assess how it impacts patient's pain responses.
Detailed description
In this trial, participants will be given ketamine at a high enough dosage to induce general anesthesia. EEG recording will be conducted during this time. Cognitive assessments and pain monitoring will be administered at various points before and after ketamine induction.
Interventions
DRUGKetamine
Subjects' brain waves will be monitored by EEG recording under ketamine general anesthesia over the course of approximately 60 minutes. Patients pain and dissociation will be assessed before the induction of ketamine and periodically after. Approximately 1 hour after ketamine induction, Midazolam will be administered to reduce patient dissociation.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Between the ages of 18 to 45 * Normal body weight and habitus, BMI less than or equal to 30 * Non-smoker * American Society of Anesthesiologists (ASA) physical status classification P1
Exclusion criteria
* Cardiovascular: myocardial infarction, coronary artery disease, peripheral vascular disease, arrhythmia, congestive heart failure, valvular disease, hypertension * Respiratory: bronchitis, chronic obstructive pulmonary disease, smoking, shortness of breath * Hepatic: hepatitis, jaundice, ascites * Neurologic: seizure, stroke, positive neurologic findings on neurologic examination, multiple sclerosis, Meniere's disease, Parkinson's disease, neuropathy, peripheral stenosis * Gastrointestinal: esophageal reflux, hiatal hernia, ulcer * Endocrine: diabetes, thyroid disease * Renal: acute or chronic severe renal insufficiency * Hematologic: blood dyscrasias, anemia, coagulopathies, on anticoagulant therapy * Musculoskeletal: prior surgery or trauma to head neck or face, arthritis, personal or family history of malignant hyperthermia * Psychiatric: history or treatment for an active psychiatric problem, depression * Reproductive: pregnancy, breast-feeding * Medications: regular use of prescription and non-prescription medications expected to affect CNS function, St. John's Wort * Allergies: labetalol, ondansetron, glycopyrrolate, ketamine, midazolam
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Pain Intensity Pre- and Post-Ketamine Induction | Approximately 125 minutes | Average Pain Intensity prior to ketamine induction, 30 minutes post ketamine, 60 minutes post ketamine, 75 minutes post ketamine, and 120 minutes post ketamine. PROMIS Pain Intensity 1a was used to assess pain delivered by a pre-calibrated pain cuff. Scale of 0 (no pain) to 10 (worst imaginable pain). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Dissociation States Score Pre- and Post-Ketamine Induction | About 125 minutes | Patients were assessed for dissociation states prior to the induction of ketamine and at 60 minutes, 75 minutes, and 120 minutes after Ketamine was administered. The Clinician Administered Dissociation States Scale was used to measure dissociation. Each section is scored 0 (not at all) to 4 (extreme), and totaled. The minimum total score is 0 (best, no dissociation at all) and the maximum total score is 92 (worst, the most dissociation). |
| Difference of the Mean Clinician Administered Dissociative States Scale Before and After Midazolam Administration | About 60 minutes | Midazolam was administered approximately 60 minutes after the administration of Ketamine in order to reduce the effects of Ketamine on dissociation. Dissociation was measured using the Clinician Administered Dissociative States Scale. Each section is scored 0 (not at all) to 4 (extreme), and totaled. The minimum total score is 0 (best, no dissociation at all) and the maximum total score is 92 (worst, the most dissociation). The difference of the mean Clinician Administered Dissociative States Scale before and after Midazolam administration was found. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Ketamine 15 subjects undergoing ketamine general anesthesia.
Subjects' brain waves will be monitored by EEG recording under ketamine general anesthesia over the course of approximately 60 minutes. Patients pain and dissociation will be assessed before the induction of ketamine and periodically after. Approximately 1 hour after ketamine induction, Midazolam will be administered to reduce patient dissociation. | 15 |
| Total | 15 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 1 |
Baseline characteristics
| Characteristic | Ketamine |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants |
| Age, Continuous | 24 years STANDARD_DEVIATION 3.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 10 Participants |
| Region of Enrollment United States | 15 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 15 |
| other Total, other adverse events | 0 / 15 |
| serious Total, serious adverse events | 0 / 15 |
Outcome results
Primary
Average Pain Intensity Pre- and Post-Ketamine Induction
Average Pain Intensity prior to ketamine induction, 30 minutes post ketamine, 60 minutes post ketamine, 75 minutes post ketamine, and 120 minutes post ketamine. PROMIS Pain Intensity 1a was used to assess pain delivered by a pre-calibrated pain cuff. Scale of 0 (no pain) to 10 (worst imaginable pain).
Time frame: Approximately 125 minutes
Population: 1 patient did not complete assessments after recovery of responsiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine EEG Dynamics | Average Pain Intensity Pre- and Post-Ketamine Induction | Pre-Ketamine | 7.9 score on a scale | Standard Deviation 0.5 |
| Ketamine EEG Dynamics | Average Pain Intensity Pre- and Post-Ketamine Induction | 30 minutes Post-Ketamine | 1.6 score on a scale | Standard Deviation 1.6 |
| Ketamine EEG Dynamics | Average Pain Intensity Pre- and Post-Ketamine Induction | 60 minutes Post-Ketamine | 4.1 score on a scale | Standard Deviation 2.2 |
| Ketamine EEG Dynamics | Average Pain Intensity Pre- and Post-Ketamine Induction | 75 minutes Post-Ketamine | 4.3 score on a scale | Standard Deviation 2.2 |
| Ketamine EEG Dynamics | Average Pain Intensity Pre- and Post-Ketamine Induction | 120 minutes Post-Ketamine | 5.4 score on a scale | Standard Deviation 2.3 |
Secondary
Average Dissociation States Score Pre- and Post-Ketamine Induction
Patients were assessed for dissociation states prior to the induction of ketamine and at 60 minutes, 75 minutes, and 120 minutes after Ketamine was administered. The Clinician Administered Dissociation States Scale was used to measure dissociation. Each section is scored 0 (not at all) to 4 (extreme), and totaled. The minimum total score is 0 (best, no dissociation at all) and the maximum total score is 92 (worst, the most dissociation).
Time frame: About 125 minutes
Population: 1 patient did not perform assessments after recovery of responsiveness.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ketamine EEG Dynamics | Average Dissociation States Score Pre- and Post-Ketamine Induction | Pre-Ketamine | 0.2 score on a scale | Standard Deviation 0.4 |
| Ketamine EEG Dynamics | Average Dissociation States Score Pre- and Post-Ketamine Induction | 60 minutes post-ketamine | 22.1 score on a scale | Standard Deviation 17 |
| Ketamine EEG Dynamics | Average Dissociation States Score Pre- and Post-Ketamine Induction | 75 minutes post-ketamine | 14.3 score on a scale | Standard Deviation 11.6 |
| Ketamine EEG Dynamics | Average Dissociation States Score Pre- and Post-Ketamine Induction | 120 minutes post-ketamine | 5.2 score on a scale | Standard Deviation 7.3 |
Secondary
Difference of the Mean Clinician Administered Dissociative States Scale Before and After Midazolam Administration
Midazolam was administered approximately 60 minutes after the administration of Ketamine in order to reduce the effects of Ketamine on dissociation. Dissociation was measured using the Clinician Administered Dissociative States Scale. Each section is scored 0 (not at all) to 4 (extreme), and totaled. The minimum total score is 0 (best, no dissociation at all) and the maximum total score is 92 (worst, the most dissociation). The difference of the mean Clinician Administered Dissociative States Scale before and after Midazolam administration was found.
Time frame: About 60 minutes
Population: 1 patient did not complete assessments after recovery of responsiveness.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Ketamine EEG Dynamics | Difference of the Mean Clinician Administered Dissociative States Scale Before and After Midazolam Administration | 10.3 score on a scale |