Pro-Epileptic Effects of IV Ketamine (Ketamin stdy)

December 6, 2025 updated by: Adem Az, Haseki Training and Research Hospital

Potential Pro-Convulsive Properties of Ketamine and Its Effects on EEG During Procedural Sedation: A Comparative Evaluation With Midazolam and Propofol

The investigators evaluated the safety and potential pro-epileptic effects of intravenous (IV) ketamine during procedural sedation in comparison with IV midazolam and IV propofol. Specifically, the study hypothesizes that IV ketamine, at doses used for procedural sedation, exhibits pro-convulsive properties, lowers the epileptic seizure threshold, and may induce interictal epileptiform discharges and/or seizures. Additionally, the investigators assessed the effects of these sedative agents on electroencephalographic (EEG) activity during procedural sedation.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Patients were randomly assigned to one of three groups: the first group received IV ketamine at a titrated dose of 0.5-1.0 mg/kg, the second group received IV midazolam at a titrated dose of 0.15-0.40 mg/kg, and the third group received IV propofol at a titrated dose of 0.5-1.0 mg/kg. Procedural sedation in all groups was supplemented with IV fentanyl, administered in small incremental boluses of 25-50 mcg to ensure adequate analgesia. Baseline EEG recordings were obtained for all patients prior to the procedure. During the procedure, EEG recordings, vital parameters-including blood pressure, heart rate, and respiratory rate-and the depth of sedation were continuously monitored for all participants. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) Scale was used to evaluate the depth of sedation.

The MOAA/S scale was applied as follows:

Score 5: Alert; responds readily to name spoken in a normal tone. Score 4: Mild sedation; lethargic response to name spoken in a normal tone. Score 3: Moderate sedation; responds only after the name is spoken loudly and/or repeatedly.

Score 2: Deep sedation; responds only after mild prodding or shaking. Score 1: Very deep sedation; unresponsive to physical stimulation. The target sedation level for patients was maintained between 2 and 3, depending on the procedural requirements. If necessary, the drug dose was carefully adjusted to increase or decrease sedation while ensuring the depth of sedation did not drop to level 1.

EEG recordings for all patients were performed. Electrodes were placed on the scalp according to the International 10-20 system, with 19 electrodes and 1 reference electrode, and the impedance of each electrode was maintained below 5 kilo-ohms. EEG recordings began with a 5-minute baseline recording during wakefulness, followed by continuous monitoring during the induction phase (administration of sedative drugs), and an additional 10-minute recording after sedation was achieved. Upon completion of the procedural intervention, EEG recordings were repeated for 10 minutes during the awakening phase and calm wakefulness.

After data collection, all EEG recordings were visually analyzed by a clinical neurophysiologist blinded to the administered drugs. EEG signals were evaluated using filters set between 0.5-70 Hz and a bipolar montage (double banana). Large-amplitude waves (>100 μV) were considered artifacts, and artifacts caused by eyelid or ocular movements were excluded from the analysis.

The recordings were analyzed for basic EEG activity, including alpha (8-12 Hz), beta (13-25 Hz), theta (4-7 Hz), delta (0.5-3.5 Hz), and gamma (25-40 Hz) rhythms, suppression-burst patterns, and their topographies. The presence of interictal epileptiform discharges, such as focal and/or generalized spike-wave, sharp wave, spike-slow wave, sharp-slow wave, and multiple spike-slow wave patterns, was noted. Additionally, clinical and/or subclinical ictal activity was documented.

Demographic data, including age, sex, comorbidities, and body weight, as well as vital parameters recorded before and during the procedure, EEG findings, and adverse effects following IV treatment, were systematically recorded.

Study Type

Interventional

Enrollment (Actual)

300

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Turkey (Türkiye)
    • Istanbul
      • Istanbul, Istanbul, Turkey (Türkiye), 34265
        • Haseki Training and Research Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

- Adults aged ≥18 years scheduled to undergo procedural sedation prior to esophagogastroduodenoscopy in the endoscopy unit were included in the study.

Exclusion Criteria:

  • patients aged <18 years,
  • pregnant or breastfeeding females,
  • patients with a known history of epilepsy, previous status epilepticus, or neurological conditions such as head trauma, brain tumors, cerebrovascular events, meningitis, or encephalitis, as well as congenital or acquired structural brain anomalies.
  • Individuals with a first-degree family history of epilepsy or who had used medications affecting the central nervous system (e.g., antidepressants, antipsychotics, sedatives, benzodiazepines, or opioids) within the previous month were also excluded.
  • Patients were also excluded if they had a known allergy or hypersensitivity to the study drugs (IV ketamine, IV midazolam, IV propofol) or to adjunctive medications used for procedural sedation (e.g., IV fentanyl).
  • Patients with a history of complications during anesthesia or previous surgical procedures, such as malignant hyperthermia or respiratory failure.
  • Patients with significant movement disorders, agitation, scalp lesions, or other conditions interfering with EEG recording.
  • Patients with severe cardiovascular disease, including uncontrolled hypertension, advanced heart failure, or arrhythmias, as well as those with oxygen saturation <90%, a high risk of respiratory depression, or severe obstructive sleep apnea syndrome.
  • Patients with severe hepatic or renal failure, or those who had undergone major surgery within the previous 6 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Screening
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Ketamine group
The Ketamine group received IV ketamine at a dosage of 0.5-1.0 mg/kg.
Drug: Ketamine
The Ketamine group received IV ketamine at a titrated dose of 0.5-1.0 mg/kg with IV fentanyl, administered in small incremental boluses of 25-50 mcg to ensure adequate analgesia.
Active Comparator: Midazolam group
The Midazolam group received IV midazolam at a dosage of 0.15-0.40 mg/kg.
Drug: Midazolam
The Midazolam group received IV midazolam at a titrated dose of 0.15-0.40 mg/kg with IV fentanyl, administered in small incremental boluses of 25-50 mcg to ensure adequate analgesia.
Active Comparator: Propofol group
The Propofol group received IV propofol at a dosage of 0.5-1.0 mg/kg.
Drug: Propofol
The Propofol group received IV propofol at a titrated dose of 0.5-1.0 mg/kg with IV fentanyl, administered in small incremental boluses of 25-50 mcg to ensure adequate analgesia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rates of interictal epileptiform discharges on EEG
Time Frame: 0, 5, and 30 min following the initial administration.
The investigators assessed the rates of interictal epileptiform discharges on EEG, including focal and/or generalized spike-wave, sharp wave, spike-slow wave, and sharp-slow wave patterns, induced by IV ketamine.
0, 5, and 30 min following the initial administration.
Rates of interictal epileptiform discharges on EEG
Time Frame: 0, 5, and 30 min following the initial administration.
The investigators assessed the rates of interictal epileptiform discharges on EEG, including focal and/or generalized spike-wave, sharp wave, spike-slow wave, and sharp-slow wave patterns, induced by IV midazolam.
0, 5, and 30 min following the initial administration.
Rates of interictal epileptiform discharges on EEG
Time Frame: 0, 5, and 30 min following the initial administration.
The investigators assessed the rates of interictal epileptiform discharges on EEG, including focal and/or generalized spike-wave, sharp wave, spike-slow wave, and sharp-slow wave patterns, induced by IV propofol.
0, 5, and 30 min following the initial administration.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Presence of subclinical seizure activity
Time Frame: 0, 5, and 30 min following the initial administration.
The investigators assessed the presence of subclinical seizure activity (ictal activity) on EEG within the ketamine group.
0, 5, and 30 min following the initial administration.
Presence of subclinical seizure activity
Time Frame: 0, 5, and 30 min following the initial administration.
The investigators assessed the presence of subclinical seizure activity (ictal activity) on EEG within the midazolam group.
0, 5, and 30 min following the initial administration.
Presence of subclinical seizure activity
Time Frame: 0, 5, and 30 min following the initial administration.
The investigators assessed the presence of subclinical seizure activity (ictal activity) on EEG within the propofol group.
0, 5, and 30 min following the initial administration.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Haseki Training and Research Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

December 1, 2024

Primary Completion (Actual)

August 30, 2025

Study Completion (Actual)

August 30, 2025

Study Registration Dates

First Submitted

December 18, 2024

First Submitted That Met QC Criteria

December 18, 2024

First Posted (Actual)

December 19, 2024

Study Record Updates

Last Update Posted (Actual)

December 15, 2025

Last Update Submitted That Met QC Criteria

December 6, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 35-2024

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Stored in non-publicly available Available on request

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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