EEG Studies of Ketamine General Anesthesia

• Sponsor: Massachusetts General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT03553758
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Actual Duration (Months): 9
• Patients Per Site Per Month: 1.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Anesthesia	Drug: Ketamine	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Electroencephalogram Studies of Induction and Recovery From Ketamine-Induced General Anesthesia
• Actual Study Start Date: Nov 1, 2018
• Actual Primary Completion Date: Feb 1, 2019
• Actual Study Completion Date: Aug 1, 2019

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketamine 15 subjects undergoing ketamine general anesthesia.	Drug: Ketamine; 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.

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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).

2. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Massachusetts General Hospital	Boston	Massachusetts	United States	02114

Sponsors and Collaborators

• Massachusetts General Hospital

Investigators

None specified.

Study Documents (Full-Text)

• Informed Consent Form - Oct 24, 2018
• Study Protocol and Statistical Analysis Plan - May 11, 2018

More Information

Publications

None provided.

• Responsible Party: Oluwaseun Johnson-Akeju, MD, MMSc, Associate Professor of Anaesthesia, Massachusetts General Hospital
• ClinicalTrials.gov Identifier: NCT03553758
• Other Study ID Numbers: 2018P000417
• First Posted: Jun 12, 2018
• Last Update Posted: Aug 26, 2020
• Last Verified: Aug 1, 2020

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Ketamine

Study Results

Participant Flow

Arm/Group Title	Ketamine
Arm/Group Description	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.
Period Title: Overall Study
STARTED	16
Completed Screening Visit	16
COMPLETED	15
NOT COMPLETED	1

Baseline Characteristics

Arm/Group Title	Ketamine
Arm/Group Description	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.
Overall Participants	15
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	15 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	24 (3.4)
Sex: Female, Male (Count of Participants)
Female	7 46.7%
Male	8 53.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	1 6.7%
Not Hispanic or Latino	14 93.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 6.7%
Asian	2 13.3%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	1 6.7%
White	10 66.7%
More than one race	0 0%
Unknown or Not Reported	1 6.7%
Region of Enrollment (participants) [Number]
United States	15 100%

Outcome Measures

1. Primary Outcome

Title	Average Pain Intensity Pre- and Post-Ketamine Induction
Description	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

Outcome Measure Data

Analysis Population Description

1 patient did not complete assessments after recovery of responsiveness.

Arm/Group Title	Ketamine EEG Dynamics
Arm/Group Description	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.
Measure Participants	14
Pre-Ketamine	7.9 (0.5)
30 minutes Post-Ketamine	1.6 (1.6)
60 minutes Post-Ketamine	4.1 (2.2)
75 minutes Post-Ketamine	4.3 (2.2)
120 minutes Post-Ketamine	5.4 (2.3)

2. Secondary Outcome

Title	Average Dissociation States Score Pre- and Post-Ketamine Induction
Description	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

Outcome Measure Data

Analysis Population Description

1 patient did not perform assessments after recovery of responsiveness.

Arm/Group Title	Ketamine
Arm/Group Description	15 subjects undergoing ketamine general anesthesia. Ketamine: 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.
Measure Participants	14
Pre-Ketamine	0.2 (0.4)
60 minutes post-ketamine	22.1 (17)
75 minutes post-ketamine	14.3 (11.6)
120 minutes post-ketamine	5.2 (7.3)

3. Secondary Outcome

Title	Difference of the Mean Clinician Administered Dissociative States Scale Before and After Midazolam Administration
Description	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

Outcome Measure Data

Analysis Population Description

1 patient did not complete assessments after recovery of responsiveness.

Arm/Group Title	Ketamine
Arm/Group Description	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.
Measure Participants	14
Mean (95% Confidence Interval) [score on a scale]	10.3

Adverse Events

Time Frame	From initiation of anesthesia during the first study visit to completion of the study visit, which was approximately 2 hours.
Adverse Event Reporting Description	Adverse events and other events were determined by regular investigator assessment and self-reporting.
Arm/Group Title	Ketamine
Arm/Group Description	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.
All Cause Mortality
	Ketamine
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Ketamine
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Other (Not Including Serious) Adverse Events
	Ketamine
	Affected / at Risk (%)	# Events
Total	0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.