Pro-Epileptic Effects of IV Ketamine

NCT ID: NCT06741930

Last Updated: 2024-12-20

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 300 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-12-01
• Study Completion Date: 2025-08-30

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.

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.

Conditions

Epilepsy; Seizure

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SCREENING
• Blinding Strategy: DOUBLE

Study Groups

Ketamine group

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

Group Type: ACTIVE_COMPARATOR

Ketamine

Intervention Type: 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.

Midazolam group

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

Group Type: ACTIVE_COMPARATOR

Midazolam

Intervention Type: 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.

Propofol group

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

Group Type: ACTIVE_COMPARATOR

Propofol

Intervention Type: 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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Haseki Training and Research Hospital

OTHER

Sponsor Role: lead

Responsible Party

Adem Az

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Haseki Training and Research Hospital

Istanbul, Istanbul, Turkey (Türkiye)

Countries

Turkey (Türkiye)

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 29870458 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 29945898 (View on PubMed)

Other Identifiers

35-2024

Identifier Type: -

Identifier Source: org_study_id