Comparison of Propofol Target-Controlled Infusion Anesthesia and Bolus Injection in Electroconvulsive Therapy

Study Overview
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Brief Summary
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Electroconvulsive therapy (ECT) serves as an effective adjuvant or alternative modality for major depressive disorder, schizophrenia, or bipolar affective disorder refractory to or contraindicated to psychopharmacological treatment. Anesthetics have been introduced into ECT sessions to alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia, hypertension, and anxiety. Propofol is highly lipid soluble and able to rapidly cross the blood-brain barrier (BBB), which leads to rapid onset of sedation and hypnosis. Meanwhile, propofol has hemodynamic depressant effect and attenuates hypertensive surge during ECT. Characteristics mentioned above make propofol one of widely used anesthetics for anesthetized ECT. Propofol can be administered with bolus injection or target-controlled infusion (TCI). Compared with bolus injection, TCI provides relatively constant concentration at site of interest based on computer simulation with input of pharmacokinetic parameters, such as age, body weight, body height, etc. However, propofol is also well known for anticonvulsant property, which may inevitably interfere with seizure propagation by electroconvulsive stimulus and diminish consequent efficacy. Thus, dosage of electrical stimulus may be increased to achieve ideal seizure quality in this setting, which also leads to higher risk of subsequent cognitive impairment. In our clinical practice, TCI system reduces total amount of propofol in comparison with bolus injection method. Therefore, we hypothesize that application of TCI system in anesthetized ECT relates to lower dosage of electrical stimulus and decreased incidence or severity of post-treatment cognitive impairment.

Detailed Description
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Electroconvulsive therapy (ECT) serves as an effective adjuvant or alternative modality for major depressive disorder, schizophrenia, or bipolar affective disorder refractory to or contraindicated to psychopharmacological treatment. Anesthetics have been introduced into ECT sessions to alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia, hypertension, and anxiety. Propofol is highly lipid soluble and able to rapidly cross the blood-brain barrier (BBB), which leads to rapid onset of sedation and hypnosis. Meanwhile, propofol has hemodynamic depressant effect and attenuates hypertensive surge during ECT. Characteristics mentioned above make propofol one of widely used anesthetics for anesthetized ECT. Propofol can be administered with bolus injection or target-controlled infusion (TCI). Compared with bolus injection, TCI provides relatively constant concentration at site of interest based on computer simulation with input of pharmacokinetic parameters, such as age, body weight, body height, etc. However, propofol is also well known for anticonvulsant property, which may inevitably interfere with seizure propagation by electroconvulsive stimulus and diminish consequent efficacy. Thus, dosage of electrical stimulus may be increased to achieve ideal seizure quality in this setting, which also leads to higher risk of subsequent cognitive impairment. In our clinical practice, TCI system reduces total amount of propofol in comparison with bolus injection method. Therefore, we hypothesize that application of TCI system in anesthetized ECT relates to lower dosage of electrical stimulus and decreased incidence or severity of post-treatment cognitive impairment.

Official Title
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Comparison of Propofol Target-Controlled Infusion Anesthesia and Bolus Injection in Electroconvulsive Therapy: A Randomized Controlled Trial

Conditions
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Depression, Schizophrenia, Bipolar Disorder, Cognitive Dysfunction

Intervention / Treatment
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* Device: Target controlled infusion, Schnider model
* Behavioral: Bolus injection of Propofol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 20 years old and 65 years old Diagnosis of major depressive disorder, bipolar disorder, and schizophrenia, compatible with SCID for DSM-5, with clinical necessity of ECT under a psychiatrist's evaluation and decision Patients with adequate visual acuity and auditory acuity without or with correction Patients or patients' legal representative signing up the informed consent Exclusion Criteria: Patients already diagnosed with neurocognitive disorder Patients with contraindications to ECT, including myocardial infarction, cerebrovascular disease, elevated intracranial pressure, intracranial angiomas, untreated bony fractures, cervical spine injury, pheochromocytoma, heart failure, sever valvular disease, deep vein thrombosis, etc. Patients with untreated substance abuse, including alcohol and illegal drugs Patients with unspecified psychiatric disorders Patients unable to cooperate

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Propofol Target Controlled Infusion Group (Group T)<br>Patients in group T underwent anesthesia with Propofol (dosage form: 10mg/mL) target controlled infusion by Schnider model, starting at concentration of effect site (Ce) of 1.5 mcg/mL and titrating to achieve Observer's Assessment of Alertness/Sedation (OAA/S) Scale level 3 (responds only after name called loudly or repeatedly). Patients were paralyzed with suxamethonium (dosage form: 20mg/mL; dosage: 1mg/kg) once adequate sedation level achieved. TCI was stopped once the psychiatrist applied electroconvulsive stimulation to patients' bilateral frontal regions. Assisted ventilation with bag-valve-mask device by experienced anesthesiologists was began since patients were sedated until adequate spontaneous respiration was regained after each single electroconvulsive therapy (ECT) session. Every patient receive total six to twelve ECT sessions, and each ECT session was conducted one day apart. | Device: Target controlled infusion, Schnider model<br>* Target controlled infusion (TCI) is an intravenous drug delivery system estimating pharmacokinetics after input of patient's data, e.g. age, sex, body height, body weight. Schnider model is one of TCI model to deliver Propofol. After target concentration at effect site (e.g. the brain) is keyed in, the computerized infusion pump will calculate dosage of bolus and infusion rate for each individual, and calculated concentration of propofol at plasma and brain will be displayed. The clinicians should evaluate the patient's sedation level in response to calculated propofol concentration and titrate target concentration to achieve desired sedation level.<br>|
| Active Comparator: Propofol Bolus Group (Group B)<br>Patients in group B underwent anesthesia with bolus of propofol for sedation, and the dosage raged between 0.75 to 1.5 mg/kg to achieve at least OAA/S scale level 3. Dosage of suxamethonium, application of electroconvulsive stimulation, ventilation maneuver, frequency of ECT session, and number of total ECT sessions were same as patients in group T. | Behavioral: Bolus injection of Propofol<br>* Bolus intravenous injection is a traditional way to deliver anesthetic, and the dosage and amount of medication is based on clinical experience and patients' response.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline Clinical Global Impression-Severity (CGI-S) | Evaluation with Clinical Global Impression-Severity (CGI-S) | through study completion, an average of one month | 
| Change from baseline Clinical Global Impression-Improvement (CGI-I) | Evaluation with Clinical Global Impression-Improvement (CGI-I) | through study completion, an average of one month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cognitive dysfunction | Evaluation with Montreal Cognitive Assessment (MoCA) | through study completion, an average of one month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Electroconvulsive therapy, Propofol, Target controlled infusion