A Prospective Randomized, Double Blind, Controlled, Safety and Non-inferiority Study of Esketamine Plus Propofol Compared to Methohexital Anesthesia for Electroconvulsive Therapy
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- antidepressant effect
研究概览
简要总结
The current anesthetic drug used as standard for ECT procedure at the Department of Psychiatry and Psychotherapy, Medical University of Vienna, is the barbiturate methohexital (Brevital®). As far as we know, methohexital is the most common anesthetic in the procedure of ECT. Only few heterogeneous randomized controlled trials to directly compare the use of (sole) ketamine and methohexital in ECT with relatively small sample sizes have been conducted so far, showing inconclusive findings: a retrospective comparison of methohexital and switch to ketamine anesthesia in 36 patients showed that ketamine prolonged seizure duration and accelerated posttreatment orientation. Others compared both drugs in terms of recovery and reorientation time showing that reorientation time was faster in the methohexital group (total N=9). Another study showed no difference in any outcome measure (depressive symptom improvement, cognition, adverse events) between both groups (total N=16, N=9 per group). Finally, a comparative investigation (total N=37, N=20 vs. N=17) detected no differences between both anesthetics but a higher systolic blood pressure posttreatment and longer motor seizure duration in the ketamine group. A favorable profile of ketamine in regards to seizure quality has been reported, however in terms of outcome measures methohexital and ketamine were similar (total N=50, N=23 vs. N=27).
The present study is designed as a prospective randomized non-inferiority trial comparing esketamine plus propofol (ratio 1:1, for better readability from now on referred to as "ketofol") to methohexital, the latter being the current standard anesthetic applied for ECT procedure at our department. Patients eligible for ECT will be randomly assigned to receive anesthesia with either ketofol or methohexital for the whole course of the individual ECT series. Group differences will be investigated both in regards to outcomes related to anesthesia, treatment-outcome and seizure quality.
Further, changes in cardiac enzyme levels before and after ECT-treatment and during the entire ECT series will be evaluated and possible group differences will be explored.
As stated above the sole/adjunct administration of ketamine as anesthetic agent for ECT has been associated with better seizure quality, similar antidepressant outcomes and anesthesia-associated events, while there is some evidence suggesting that the use of ketamine might present some advantages to other anesthetics in terms of cognitive side-effects accompanying ECT. Therefore, the aim of the present study will be to establish ketofol as a new standard for anesthesia at our Department.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
盲法说明
Randomization of the study drug will be done using the software www.meduniwien.ac.at/randomizer according to consecutive CRF numbers. Stratification according to baseline HAMD17 scores (3 groups: HAMD 23-30, HAMD 30-40, HAMD>40), age and previous ECT (yes/no) will be performed Participants and treating psychiatrists will be unaware or the anesthetic used; anesthetists will know the substance that it aministered during ECT
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •male or female inpatients
- •age ≥ 18 years
- •ICD-11 diagnosis of severe uni- or bipolar depression (F32.2, F32.2, F33.2, F33.3, F31.4, F31.5)
- •Hamilton Depression Rating Scale HAMD17 ≥ 24
- •ability to understand and willingness to sign written informed consent document
- •negative urine pregnancy test in women
- •anesthesiological approval for ECT (Classification of the American Society of Anesthesiologists ASA ≤ 3)
- •antidepressant and antipsychotic medication in steady state for at least 7 days prior to first ECT treatment
排除标准
- •severe somatic or neurological disease (esp. current or previous history of intracranial hypertension, uncontrolled severe hypertension, bleeds or aneurysm, recent myocardial infarction)
- •current or past history of schizophrenia or schizoaffective disorder
- •clinical relevant abnormalities on a general physical examination and routine laboratory screening
- •pregnancy, breast feeding
- •known allergy to the study drugs or compounds of the latter
研究组 & 干预措施
Methohexital
Initial dose: methohexital 1 mg/kg (≙ 80 mg methohexital in a subject with 80 kg). If sufficient hypnosis is not achieved with the initial dose further doses of 10 mg methohexital will be administered until sufficient depth of anesthesia according to defined criteria is achieved. Criteria for sufficient depth of anesthesia will be comprised by a) the abolition of the eye-lash reflex b) absence of motor reaction upon inflation of the tourniquet.
Maintenance dose: none (The drug combination is injected in order to initiate anesthesia) Route of administration: intravenous Duration: few seconds to initiate anesthesia. The procedure will be repeated for each ECT session.
干预措施: Methohexital (Drug)
Ketofol
Esketamine and propofol will be prepared shortly before injection by the nurse anesthetist as follows: 4 ml esketamine 25mg/ml, 6ml NaCl (0,9%), 10ml propofol (10mg/ml). The stability of ketamine-propofol mixtures (undiluted, 50:50 ratio) in one syringe has been documented for up to 3 hours.
Initial dose: esketamine 0,5 mg/kg + propofol 0,5 mg/kg (≙ 40 mg esketamine + 40 mg propofol in a subject with 80 kg). If sufficient hypnosis is not achieved with the initial dose further doses of 5mg esketamine and 5 mg propofol will be administered until a sufficient depth of anesthesia is achieved.
Maintenance dose: none (The drug combination is injected in order to initiate anesthesia) Route of administration: intravenous Duration: few seconds to initiate anesthesia. The procedure will be repeated for each ECT session
干预措施: Ketofol (Drug)
结局指标
主要结局
antidepressant effect
时间窗: 4 weeks
• HAMD17 change between baseline and post-ECT in both treatment arms over a series of 8 ECT sessions
recovery time
时间窗: 4 weeks
Mean recovery time over 8 ECT sessions in both treatment arms
次要结局
- adverse events(4 weeks)
- concomitant medication(4 weeks)
- cognition(4 weeks)
- time to reorientation(4 weeks)
- seizure quality(4 weeks)
研究者
Pia Baldinger-Melich
Assoc.Prof.
Medical University of Vienna