Pro-Epileptic Effects of IV Ketamine

NCT06741930 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: 35-2024
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Seizure; Epilepsy

Keywords

ketamine; midazolam; propofol; epilepsy; Procedural Sedation; Pro-Convulsive Effects

Outcome Measures

Primary Outcomes (3)

• Rates of interictal epileptiform discharges on EEG

  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

  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

  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 Outcomes (3)

• Presence of subclinical seizure activity

  0, 5, and 30 min following the initial administration.

• Presence of subclinical seizure activity

  0, 5, and 30 min following the initial administration.

• Presence of subclinical seizure activity

  0, 5, and 30 min following the initial administration.

Study Arms (3)

Ketamine group

ACTIVE COMPARATOR

The Ketamine group received IV ketamine at a dosage of 0.5-1.0 mg/kg.

Drug: Ketamine

Midazolam group

ACTIVE COMPARATOR

The Midazolam group received IV midazolam at a dosage of 0.15-0.40 mg/kg.

Drug: Midazolam

Propofol group

ACTIVE COMPARATOR

The Propofol group received IV propofol at a dosage of 0.5-1.0 mg/kg.

Drug: Propofol

Interventions

Midazolam DRUG

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.

Midazolam group

Propofol DRUG

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.

Propofol group

Ketamine DRUG

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.

Ketamine group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Haseki Training and Research Hospital: lead

Study Sites (1)

Haseki Training and Research Hospital

Istanbul, Istanbul, 34265, Turkey (Türkiye)

Location

Related Publications (6)

• Az A, Dogan Y. Unexpected consequences: A case of ketamine-induced seizure in procedural sedation. Turk J Emerg Med. 2024 Oct 1;24(4):259-261. doi: 10.4103/tjem.tjem_67_24. eCollection 2024 Oct-Dec.

  PMID: 39564442 RESULT

• Kim JH, Lee CK, Yu SH, Min BD, Chung CE, Kim DC. Ketamine-induced generalized convulsive seizure during procedural sedation. Arch Craniofac Surg. 2021 Apr;22(2):119-121. doi: 10.7181/acfs.2021.00094. Epub 2021 Apr 20.

  PMID: 33957739 RESULT

• Shehata IM, Kohaf NA, ElSayed MW, Latifi K, Aboutaleb AM, Kaye AD. Ketamine: Pro or antiepileptic agent? A systematic review. Heliyon. 2024 Jan 10;10(2):e24433. doi: 10.1016/j.heliyon.2024.e24433. eCollection 2024 Jan 30.

  PMID: 38293492 RESULT

• Besha A, Adamu Y, Mulugeta H, Zemedkun A, Destaw B. Evidence-based guideline on management of status epilepticus in adult intensive care unit in resource-limited settings: a review article. Ann Med Surg (Lond). 2023 Apr 17;85(6):2714-2720. doi: 10.1097/MS9.0000000000000625. eCollection 2023 Jun.

  PMID: 37363462 RESULT

• Cohen SP, Bhatia A, Buvanendran A, Schwenk ES, Wasan AD, Hurley RW, Viscusi ER, Narouze S, Davis FN, Ritchie EC, Lubenow TR, Hooten WM. Consensus Guidelines on the Use of Intravenous Ketamine Infusions for Chronic Pain From the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists. Reg Anesth Pain Med. 2018 Jul;43(5):521-546. doi: 10.1097/AAP.0000000000000808.

  PMID: 29870458 RESULT

• Zanos P, Moaddel R, Morris PJ, Riggs LM, Highland JN, Georgiou P, Pereira EFR, Albuquerque EX, Thomas CJ, Zarate CA Jr, Gould TD. Ketamine and Ketamine Metabolite Pharmacology: Insights into Therapeutic Mechanisms. Pharmacol Rev. 2018 Jul;70(3):621-660. doi: 10.1124/pr.117.015198.

  PMID: 29945898 RESULT

MeSH Terms

Conditions

Epilepsy; Seizures

Interventions

Ketamine; Midazolam; Propofol

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: In this double-blind study, participants were randomly assigned to one of the three treatment groups (Ketamine, Midazolam, or Propofol) using a sealed envelope randomization. Both the physicians who assessed the results and the patients were blinded to the assigned group. Each participant was assigned an identification number indicating the treatment group. An emergency nurse prepared the treatment solutions immediately before administration, based on the assigned identification number, and stored them in labeled containers with no indication of their contents. A clinician with 32 years of experience, who was blinded to the study's null hypothesis and did not participate in the evaluation of results, administered the treatments and recorded patient data onto a predesigned case data form. Another physician with 27 years of experience, who was not present during the treatment, assessed the EEG recordings.
• Purpose: SCREENING
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Single center

Study Record Dates

• First Submitted: December 18, 2024
• First Posted: December 19, 2024
• Study Start: December 1, 2024
• Primary Completion: August 30, 2025
• Study Completion: August 30, 2025
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

TU (1)