EEG Studies of Ketamine General Anesthesia

• ClinicalTrials.gov Identifier: NCT03553758
• Recruitment Status: Completed
• First Posted: June 12, 2018
• Results First Posted: August 26, 2020
• Last Update Posted: August 26, 2020
• Sponsor: Massachusetts General Hospital
• Information provided by (Responsible Party): Oluwaseun Johnson-Akeju, MD, MMSc, Massachusetts General Hospital

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 (Clinical Trial)
• 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: November 1, 2018
• Actual Primary Completion Date: February 1, 2019
• Actual Study Completion Date: August 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 45 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

  Study Documents (Full-Text)

Documents provided by Oluwaseun Johnson-Akeju, MD, MMSc, Massachusetts General Hospital:

Informed Consent Form  [PDF] October 24, 2018

Study Protocol and Statistical Analysis Plan  [PDF] May 11, 2018

More Information

• 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: June 12, 2018
• Results First Posted: August 26, 2020
• Last Update Posted: August 26, 2020
• Last Verified: August 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; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anesthetics, Dissociative; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Central Nervous System Depressants; Excitatory Amino Acid Antagonists; Excitatory Amino Acid Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action