Potential Pro-Convulsive Properties of Ketamine and Its Effects on EEG During Procedural Sedation: A Comparative Evaluation With Midazolam and Propofol
Trial Snapshot
- Phase
- Phase 4
- Status
- Completed
- Sponsor
- Enrollment
- 300
- Locations
- 1
- Primary Endpoint
- Rates of interictal epileptiform discharges on EEG
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Screening
- Masking
- Double (Participant, Outcomes Assessor)
Masking Description
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.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Ketamine group
The Ketamine group received IV ketamine at a dosage of 0.5-1.0 mg/kg.
Intervention: Ketamine (Drug)
Midazolam group
The Midazolam group received IV midazolam at a dosage of 0.15-0.40 mg/kg.
Intervention: Midazolam (Drug)
Propofol group
The Propofol group received IV propofol at a dosage of 0.5-1.0 mg/kg.
Intervention: Propofol (Drug)
Outcomes
Primary Outcomes
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.
Secondary Outcomes
- Presence of subclinical seizure activity(0, 5, and 30 min following the initial administration.)
Investigators
Adem Az
Principal Investigator
Haseki Training and Research Hospital