ORIGINAL STUDY
Comparison of Propofol, Etomidate, and Thiopental in Anesthesia for Electroconvulsive Therapy A Randomized, Double-blind Clinical Trial Ozge Canbek, MD,* Derya Ipekcıoglu, MD,† Okan Oktay Menges, MD,‡ Murat Ilhan Atagun, MD,§ Nesrin Karamustafalıoglu, MD,† Ozlem Zekiye Cetinkaya, MD,† and Mehmet Cem Ilnem, MD† Objectives: This study aimed to compare the effects of propofol, thiopental, and etomidate, which are routinely used in anesthesia for electroconvulsive therapy (ECT), on the cardiovascular system, seizure variables, recovery, cognitive functions, and response to treatment. Methods: Male patients hospitalized at the Seventh Psychiatry Clinics of the Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery who were treated with ECT were investigated prospectively. The effects on cardiovascular system parameters (heart rate, blood pressure, and blood oxygenation), seizure variables (duration and intensity of seizure), and recovery variables were recorded at every session, on prespecified time points, and the findings of the first session were used in this evaluation. In addition, clinical responses to treatment were evaluated with tests of cognitive functions before and after a course of ECT. Adverse effects were recorded. Results: The sociodemographic characteristics of the 3 treatment groups were similar. There were no significant differences among the groups in terms of effects on cardiovascular system variables, seizure variables, and cognitive functions. The clinical response to ECT was good in all groups, without any significant differences. Conclusions: Propofol, etomidate, and thiopental are associated with similar safety and efficacy profiles. Key Words: electroconvulsive therapy, general anesthesia, seizure variables, recovery, adverse effect, clinical efficacy (J ECT 2015;31: 91–97)
E
lectroconvulsive therapy (ECT) dates back to the initial days of modern psychiatry.1–4 Electroconvulsive therapy is indicated in the treatment of major depressive disorder, manic episode, schizophrenic exacerbation, catatonia, and other serious psychiatric disorders.1,5–8 This modality is based on the electrical stimulation of the brain tissues and creation of an epileptic seizure. It was first used by Cerletti and Bini in 1938, after which it became part of the clinical practice.1,5,9–13 It was done without anesthesia until the end of 1940s, after which general anesthetics were started to be used. The technological developments in the last 30 years have increased the efficacy of ECT while decreasing its adverse effects.1,3,5,11,14 Standard ECT application consists of administration of muscle relaxants and anesthetic agents, after which a seizure is induced with an electrical stimulation.15 Successful ECT requires close collaboration between the psychiatrist and the anesthesiologist.16 From the *ECT Center, and †Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul; ‡Faruk Sukan Hospital, Konya and §Department of Psychiatry, School of Medicine, Yildirim Beyazit University, Ankara, Turkey. Received for publication March 17, 2014; accepted August 28, 2014. Reprints: Ozge Canbek, MD, ECT Center, Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery, 34147 Bakırköy, Istanbul, Turkey (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000190
An anesthetic agent with a rapid onset and short duration of action and with a minimal effect on the threshold and duration of seizures as well as hemodynamic parameters, which enables recovery in a short time, is searched for a safe, comfortable anesthesia, with few adverse effects and no effects on the psychiatric treatment. The more comfortable the treatment, the better will be the patient’s compliance and satisfaction. The most frequently used anesthesiologic agents are methohexital, thiopental, etomidate, propofol, ketamine, and sevoflurane. Methohexital, which is considered as the criterion standard, is an effective and cheap anesthetic agent with a fast onset of action, minimal anticonvulsant activity, and a fast recovery.5,8,15,17,18 This agent is not present in Turkey, and routinely used anesthetic agents are propofol, etomidate, and thiopental. Propofol is a fast-acting, nonbarbiturate anesthetic agent with antihypertensive properties, which has the negative features of increasing the seizure threshold and shortening seizure duration. Etomidate is a nonbarbiturate imidazolic derivative. Its effect and metabolism are rapid, and it has a minimal effect on the seizure threshold and cardiovascular system. Its main disadvantages are myoclonus and pain at the injection site. Thiopental is a barbiturate anesthetic agent with characteristics similar to methohexital. Sinus bradycardia and premature ventricular beats are more frequently seen with this medication.5,17,19,20 We aimed to compare the effects of 3 anesthetic agents (propofol, etomidate, and thiopental) that are routinely used in ECT anesthesia on the cardiovascular system, seizure, recovery, cognitive functions, and response to treatment in a prospective, double-blind study.
MATERIALS AND METHODS Patients The patients were male patients hospitalized at the Male Patient Ward of Seventh Psychiatry Clinics of Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery, in whom treatment with ECT was deemed necessary. The psychiatric diagnoses of these patients are presented in Table 1. A total of 56 patients aged between 20 and 60 years who did not have a previously diagnosed cardiovascular disorder were included, between August 2010 and May 2011, and 51 patients completed the study. The patients were randomized to 3 groups, in which 1 anesthetic agent was used in all sessions. The effects on cardiovascular system parameters (heart rate [HR], blood pressure, and blood oxygenation), seizure variables (the duration and intensity of seizure), and recovery variables were recorded at every session on prespecified time points. The findings of the first ECT session were used in the evaluation. Adverse effects were recorded. In addition, clinical responses to treatment were evaluated with tests of cognitive functions before and after a course of ECT.
Journal of ECT • Volume 31, Number 2, June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
91
Journal of ECT • Volume 31, Number 2, June 2015
Canbek et al
TABLE 1. The Distribution of Diagnoses in the 3 Groups Propofol, n (%) Unipolar depression Bipolar affective disorder, mania Schizophrenia Schizoaffective disorder Atypical psychosis Total
Etomidate, n (%)
Thiopental, n (%)
— 4 (25)
5 (25) 6 (30) 8 (40) 1 (5) — 20 (39.21)
— 7 (47)
9 (56) — 3 (19) 16 (31.37)
6 (40) — 2 (13) 15 (29.41)
We used a double-blind design, where the patients, anesthesiologists, and raters were blinded in terms of the anesthetic agent. One anesthesiologist (unblinded) administered anesthesia at all sessions and remained as an observer in case of emergencies, whereas another anesthesiologist and a nurse (who were blinded) recorded all seizure and anesthesia parameters. The patients were informed about the study, and written informed consents were obtained from the patients and/or their relatives/representatives. In addition, approval from the institutional ethics committee was obtained. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.
Assessments All patients were thoroughly evaluated before entering the study, which included physical examination by a physician and an anesthesiologist. Patients with any cardiovascular disorder (including arterial hypertension) were excluded. No patients were taking any antihypertensive medications. All patients were class I to II according to American Society of Anesthesiologists (ASA) criteria (50 [98.03%] patients were ASA I and 1 [1.97%] patient was ASA II. The decisions on diagnosis and ECT indications were given by the patients’ attending psychiatrists. At least 5 sessions (range, 5–14) were applied to all patients, who were considered acceptable for evaluation of clinical response. Mini-Mental State Examination (MMSE) was applied to the patients 1 day before the first ECT session and 1 day after the last ECT session. Clinical response to treatment was evaluated as “no response,” “partial response,” and “good response” and additional psychiatric scales were used for evaluation. Brief Psychiatric Rating Scale (BPRS) was used in all patients, Scale for the Assessment of Positive Symptoms (SAPS) was used in patients with psychotic disorder, Young Mania Rating Scale (YMRS) was used in patients with mania, and Hamilton Depression Rating Scale was used in patients with depression. The last ECT session was decided by the treating psychiatrist. When no clinically significant changes were observed after 2
consequent sessions, ECT treatment was ended. The numbers of sessions and responses to treatment are presented in Table 2. Two patients were excluded because of withdrawal of informed consent, 1 patient left the hospital without permission, 1 patient was excluded because of a change of anesthetic agent, and 1 patient was excluded because of premature termination of therapy due to prolonged (>24 hours) bradycardia, which occurred after the first session. Among the excluded patients, 3 patients were on propofol, 1 patient was on etomidate, and 1 patient was on thiopental.
Concomitant Medications All patients were taking combinations of psychotropic medications at maximally tolerated doses, without clinical improvement, and ECT treatment was considered necessary by their attending psychiatrists. Thus, their usual psychopharmacological therapy continued during the course of study. The medications of the patients are presented in Table 3. The pharmacotherapy of the patients was not changed or restricted in any way in accordance with the protocol of this study. The total number of patients is not adequate for a comparison of the effects of different pharmacoactive medications on the response to ECT.
ECT PROCEDURE Bitemporofrontal ECT was administered with a Thymatron IV device (Somatics Inc, Lake Bluff, Ill) at the ECT center of Bakırköy, 3 times a week, every other day, in the morning. The patients were fasted for 6 hours before the procedure. The ECT application electrodes were bilaterally placed at the temporofrontal regions, whereas ECT recording electrodes were placed at the frontal and mastoid regions. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP), HR, as well as body temperature were measured and recorded before ECT. Ventilation was maintained with a mask. Pulse oximeter (Nonin 2500A pulse oximeter) was placed at the index fingers of the patients, and oxygen saturation was monitored. Stimulus dosage was adjusted in accordance with “half-age method.” Seizures shorter than 20 seconds were considered inadequate, and the stimulation dose was increased 50%, with a maximum of 3 times in a session. Additional anesthetics or muscle relaxants were not required.
Anesthetic Medications The dose of propofol was 0.75 to 1.0 mg/kg, the dose of etomidate was 0.15 to 0.25 mg/kg, and the dose of thiopental was 1.5 to 2.5 mg/kg. The dose of muscle relaxant (ie, succinylcholine) was 0.5 mg/kg. The anesthetic was selected in accordance with a randomization table. A total of 20 (39.22%) patients were TABLE 3. Medications That Were Used by the Patients During the Study Propofol Etomidate Thiopental
TABLE 2. The Distribution of Responses to Treatment of Patients According to Number of Sessions n
Good response Partial response No response
5
6
7
8
9
10
11
12
14
2 — —
3 1 —
11 4 —
6 2 —
6 1 2
4 2 —
1 2 —
2 — 1
— 1 —
n indicates number of session.
92
www.ectjournal.com
Haloperidol Haloperidol + quetiapine Haloperidol + chlorpromazine Haloperidol + quetiapine + zuclopenthixole Haloperidol + venlafaxine Haloperidol + olanzapine Quetiapine + mirtazapine + sertraline Total
2 12 3 2
2 9 1 1
— 13 1 —
1 — —
— 2 —
— 1 1
20
15
16
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 2, June 2015
5 8 40
1–15 5–12 30–60
2.56 1.39 8.54 1.52 2.14 0.83 0.91 0.25 2.36 21–40 60–90 5–11 29 70 5
4 8 40
1–22 5–14 30–60
29.1 ± 4.7 71.3 ± 8.2 6.5 ± 2.2 2 (13.3) 13 (86.7) 7 (46.7) 4.9 ± 3.6 8.1 ± 1.7 39.3 ± 8.8 22–49 55–100 5–15 32 80 8
3 8 40
1–25 6–12 30–60
33.9 ± 9.0 78.3 ± 11.5 8.9 ± 3.7 3 (18.8) 12 (75) 8 (50) 6.6 ± 6.6 8.6 ± 2.5 42.5 ± 7.7 23–58 48–102 5–15 34 69 7
Mean ± SD/n (%) Minimum-Maximum Median
Propofol
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
df = 2. *One-way ANOVA. †Kruskal-Wallis test. ‡χ2 test.
A total of 56 patients were included in this study, and 51 patients completed the study. The sociodemographic and clinical characteristics of the patients are summarized in Table 4. The psychiatric diagnoses of the patients in this series were unipolar major depression in 5 (9.80%) patients (with psychotic features except 1 patient), bipolar disorder (manic episode) in 17 (33.33%) patients, schizophrenia in 23 (45%) patients, schizoaffective disorder in 1 (1.96%) patient, and atypical psychosis in 5 (9.80%) patients. The indications for ECT were as follows: unresponsiveness to other therapies in 16 patients, risk for suicide in 5 patients, risk for homicide in 7 patients, risk for suicide and
35.0 ± 8.9 73.6 ± 14.4 7.9 ± 3.1 6 (30) 13 (65) 8 (40) 4.2 ± 5.3 8.4 ± 1.6 39.0 ± 7.9
Sociodemographic and Clinical Characteristics
Mean ± SD/n (%)
RESULTS
TABLE 4. Sociodemographic and Clinical Characteristics
The results of the first session were used for the statistical analysis of cardiovascular, recovery, and seizure findings. Means, SDs, medians, minimal/maximal values, rates, and frequencies were used in the descriptive statistics. A P value of less than 0.05 was accepted as statistically significant. The KolmogorovSmirnov test was performed to examine the distribution characteristics of the variables. According to distribution characteristics, continuous variables were compared with repeated-measures analysis of variance (ANOVA), 1-way ANOVA, and Kruskal-Wallis tests. The Tukey test was performed for post hoc comparisons. Cardiovascular results were compared with repeated-measures ANOVA. Response to treatments as measured using the YMRS, the BPRS, and the SAPS was compared with the Kruskal-Wallis test and the ANOVA. In the ANOVAs and the Kruskal-Wallis tests, the dependent variables were anesthetic groups. Paired samples t test and Wilcoxon test were used for intragroup comparisons between measurements done before and after session. The χ2 test was used to compare categorical variables. Details of the tests are presented in the footnotes of the tables. Statistical Package for the Social Sciences version 22.0 software was used in the statistical analysis.
Etomidate
Statistical Analysis
Median
Electroencephalogram (EEG) was automatically recorded using a Thymatron IV device. Electroencephalographic duration, HR (baseline and peak), seizure energy index, seizure concordance index, and postictal suppression index (PSI) were calculated using the ECT device. The duration of seizure in EEG was detected using the device and also observed by the investigators. Motor seizure activity was observed and measured with a chronometer. The seizure intensity was evaluated on a scale of 1 to 5.21
Minimum-Maximum
Mean ± SD/n (%)
Electrophysiologic Evaluation
Age, y* Weight, kg* Duration of education, y† Marital status (married)‡ Nicotine addiction‡ History of ECT‡ No. days in hospital* No. sessions* Dose of succinylcholine, IU*
Thiopental
The duration of anesthesia was recorded with a chronometer, starting with administration of anesthetic and time to spontaneous breathing, sufficient breathing, and opening of the eyes in response to verbal instructions; the modified Aldrete score and time to leave the recovery room were also recorded.
Median
Recovery Findings
Minimum-Maximum
F/χ2
P
anesthetized with propofol; 16 (31.37%), with etomidate; and 15 (29.41%), with thiopental. Cardiovascular effects were assessed through monitoring the SBP and DBP levels as well as HR with a noninvasive digital monitor (Braun BP4000). Measurements were recorded at 7 time points: preparation, anesthesia induction, seizure, postictal first minute, postictal fifth minute, postictal 10th minute, and postictal 30th minute.
0.088 0.259 0.603 0.468 0.346 0.380 0.411 0.783 0.307
Comparison of Propofol, Etomidate, and Thiopental
www.ectjournal.com
93
Journal of ECT • Volume 31, Number 2, June 2015
Canbek et al
homicide in 2 patients, catatonia in 2 patients, excitation in 1 patient, excitation and unresponsiveness in 3 patients, risk for homicide and excitation in 6 patients, as well as risk for homicide and unresponsiveness in 9 patients. The distribution of adverse effects in the 3 groups is presented in Table 5. There were no differences among the anesthetic agents in terms of adverse effects. All adverse effects resolved spontaneously. There were no major complications or death during or after ECT.
Cardiovascular System Findings All of the cardiovascular system (CVS) variables of the first ECT session are presented in Table 6. Heart rate showed a significant increase in the seizure period in comparison with the preparation period in all 3 groups, without any significant intergroup differences. The SBP showed a significant increase during the seizure in comparison with the preparation period in all 3 groups, also without any significant intergroup differences. Systolic blood pressure was significantly lower at the 30’ postictal evaluation in comparison with the preparation period in the propofol group, whereas there were no significant differences between the 30’ postictal evaluation and the preparation period in the etomidate and thiopental groups. The DBP showed a significant increase during the seizure in comparison with the preparation period in all 3 groups, without any significant intergroup differences.
Seizure Variables Seizure variables are presented in Table 7. Motor and EEG seizure, maximum sustained coherence, and PSI did not show a significant difference among the 3 groups.
Recovery Variables Recovery variables are presented in Table 7. Spontaneous respiration returned earlier in the propofol group in comparison with the thiopental group. Time to opening the eyes was significantly shorter in the propofol group in comparison with the thiopental group. There were no significant differences among the propofol, etomidate, and thiopental groups in terms of time to TABLE 5. The Distribution of Adverse Effects Anesthetic Agents Adverse Effect Hypertension Bradycardia Tachycardia Prolonged seizure >120 s Confusion Excitation Amnesia Muscle-joint pain Hypersalivation Late recovery
Propofol (n = 20)
Etomidate (n = 16)
Thiopental (n = 15)
1 0 1 1 1 2 1 0 2 1 10
1 2 0 1 2 0 0 2 2 0 10
0 0 1 4 3 0 0 0 1 0 9
Adverse effects were observed in 10 (50%) patients of the propofol group, 10 (62.5%) patients of the etomidate group, and 9 (60%) patients of the thiopental group (χ2 = 0.65, P = 0.722).
94
www.ectjournal.com
sufficient respiration, time to Aldrete of higher than 9, and time to leave the room.
Clinical Responses and Cognitive Functions Clinical responses and cognitive functions are presented in Table 8. The posttreatment BPRS, SAPS, and YMRS values showed a significant decrease in comparison with the pretreatment values in all 3 groups, without any significant differences among groups. The pretreatment MMSE values and posttreatment MMSE values in 3 groups did not show significant differences.
DISCUSSION In this study comparing the effects of 3 frequently used anesthetic agents in ECT on recovery, cardiovascular variables, cognitive functions, and response to treatment, the only significant differences among the agents are lower SBP with propofol in the 30' postictal measurement and shorter time to spontaneous respiration and time to opening the eyes with propofol. Except these, there were no significant differences among the groups in other cardiovascular system findings. Erdil et al22 have observed a more stable hemodynamic response with propofol in comparison with etomidate in their study evaluating patients with major depressive disorder and recommended the use of this agent in ECT anesthesia. Gazdag et al20 have found better hemodynamic effects of propofol in comparison with etomidate in their study comparing etomidate and propofol in patients with schizophrenia and depression. The differences between studies may be caused by different characteristics (age, diagnosis, etc) of the patient populations. The propofol group recovered faster than the other 2 groups in our study. Rosa et al17,19 have detected similar effects with propofol in their studies comparing etomidate, propofol, and thiopental in patients with major depression. No differences were found between recovery findings with etomidate and thiopental in the study by Abdollahi et al,23 whereas the longest recovery period was observed with etomidate by Avramov et al.24 Hooten and Rasmussen25 evaluated 41 studies investigating 14 anesthetic agents and found that the recovery periods were longer with anesthetic agents with longer seizure durations but did not find any significant differences among the anesthetic agents in terms of recovery. There were no intergroup differences in the EEG and motor seizure durations in our study. Bauer et al26 have found that the duration of seizure was significantly shorter with propofol, but this did not cause a difference in clinical improvement in their study comparing propofol and thiopental in patients with depression. Omprakash et al27 also found similar seizure features. Generally, the duration of seizure was longer with etomidate in many studies.15,24 Gazdag et al20 found longer motor and EEG seizures with etomidate in their study comparing etomidate and propofol in patients with schizophrenia and depression. Avramov et al24 have found that the duration of seizure did not decrease in a dosedependent fashion with etomidate in their study comparing methohexital, etomidate, and propofol. Hooten and Rasmussen25 had found the longest seizure durations with methohexital. The most frequent adverse effects were prolonged seizure, early confusion, and hypersalivation. Omprakash et al27 have reported that, among the most frequently seen adverse effects, arrhythmias and nausea occurred more frequently in patients who were given thiopental and that pain at the injection site was more frequent in patients who were given propofol. One of the most important findings in the present study is the good response to treatment in all groups. Purtuloğlu et al28 had © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation Peak HR Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation SBP Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation DBP Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Propofol
Median Minimum-Maximum
96.9 ± 2.3 98 92–100 97.6 ± 2.4 98 92–100 98.9 ± 1.4 99 94–100 97.2 ± 3.6 99 86–100 93.6 ± 3.4 94 86–98 93.6 ± 3.0 94 86–98 95.0 ± 2.7 96 88–98 df = 6/F = 17.81/P < 0.001 90.4 ± 18.9 87 66–139 95.6 ± 20.0 94 67–146 110.9 ± 38.0 96 61–180 91.6 ± 20.0 84 67–123 90.6 ± 17.3 92 59–124 93.9 ± 20.7 92 65–127 89.8 86 68–126 df = 6/F = 4.14/P = 0.029 124.1 ± 18.3 122 69–158 129.2 ± 24.8 125 97–182 164.1 ± 45.2 154 86–259 136.9 ± 29.0 136 87–204 123.7 ± 25.4 123 77–177 115.6 ± 16.6 115 98–159 117.6 ± 16.5 118 84–146 df = 6/F = 9.77/P < 0.001 76.8 ± 12.4 74 45–105 84.8 ± 14.9 84 49–106 94.3 ± 23.1 93 63–150 77.1 ± 16.1 76 50–108 75.0 ± 19.7 70 41–106 69.2 ± 14.2 70 43–91 72.6 ± 15.8 71 49–104 df = 6/F = 8.56/P < 0.001
Repeated-measures ANOVA.
SPO2
Mean ± SD
TABLE 6. Cardiovascular Findings Etomidate Median Minimum-Maximum
96.8 ± 1.3 97 95–99 98.3 ± 1.5 99 96–100 98.8 ± 2.4 99 90–100 97.3 ± 1.6 98 94–99 94.1 ± 3.8 95 85–99 93.1 ± 3.1 94 87–99 94.3 ± 2.7 95 88–97 df = 6/F = 15.99/P < 0.001 83.2 ± 14.3 80 63–115 98.3 ± 18.5 104 61–126 122.8 ± 52.0 126 49–196 87.1 ± 25.6 78 57–157 88.4 ± 12.4 88 58–108 91.0 ± 15.1 96 57–115 87.8 ± 18.7 91 53–120 df = 6/F = 4.80/P = 0.016 126.6 ± 20.2 120 99–165 137.3 ± 20.0 135 103–180 195.1 ± 44.4 187 120–268 141.4 ± 19.0 139 110–197 126.4 ± 14.9 124 107–153 120.6 ± 14.3 116 103–145 126.2 ± 23.3 122 101–192 df = 6/F = 16.48/P < 0.001 77.0 ± 13.3 75 60–103 90.8 ± 12.8 96 70–106 99.1 ± 22.4 105 50–146 82.5 ± 17.3 81 50–106 72.8 ± 15.0 71 43–105 69.1 ± 17.2 72 45–105 76.9 ± 18.0 73 47–106 df = 6/F = 8.17/P < 0.001
Mean ± SD
Thiopental Median Minimum-Maximum
96.5 ± 2.2 96 91–99 98.7 ± 0.8 99 97–100 98.2 ± 2.5 99 90–100 98.1 ± 2.0 99 93–100 94.9 ± 4.8 97 84–100 94.7 ± 3.5 96 88–99 93.8 ± 3.4 94 87–98 df = 6/F = 17.81/P < 0.001 80.7 ± 16.3 81 54–110 96.1 ± 15.6 95 71–124 99.9 ± 34.2 94 52–160 88.9 ± 21.3 93 53–130 90.5 ± 17.1 93 63–115 87.3 ± 16.0 83 67–120 84.6 ± 15.3 80 64–117 df = 6/F = 2.69/P = 0.079 126.7 ± 19.1 124 102–179 133.3 ± 21.5 134 103–182 178.8 ± 42.5 179 121–252 137.2 ± 22.2 131 110–180 117.9 ± 22.3 117 86–170 112.2 ± 12.8 109 97–135 109.7 ± 13.8 110 93–138 df = 6/F = 8.06/P < 0.001 75.6 ± 12.1 75 57–105 88.1 ± 10.3 87 70–104 105.3 ± 28.4 100 68–149 82.7 ± 12.2 81 64–105 69.4 ± 16.3 71 50–104 68.1 ± 10.4 65 56–92 63.8 ± 7.6 60 55–82 df = 6/F = 4.51/P < 0.001
Mean ± SD
0.356
P
0.266
0.361
1.27
1.13
0.727 0.720
1.12
F/χ2
Journal of ECT • Volume 31, Number 2, June 2015 Comparison of Propofol, Etomidate, and Thiopental
www.ectjournal.com
95
96
www.ectjournal.com
3.2 ± 0.9 4.4 ± 1.2 7.7 ± 2.8 9.1 ± 2.5 9.9 ± 2.4 41.8 ± 17.0 62.6 ± 31.6 90.7 ± 19.5 85.6 ± 9.3
3 4 7 9 9 40 53 96 87
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
df = 2. *Kruskal-Wallis test. †Wilcoxon t test. ‡One-way ANOVA. §Paired samples.
Before treatment After treatment Before/after change† YMRS* Before treatment After treatment Before/after change† MMSE* Before treatment After treatment Before/after change† SAPS‡ Before treatment After treatment Before/after change§
BPRS*
48.7 ± 23.9 16.8 ± 23.6
17.2 ± 12.0 24.8 ± 4.2
32.5 ± 8.1 1.5 ± 1.2
39.3 ± 12.7 9.6 ± 12.6
Mean ± SD
Etomidate
11–83 0–70
0–30 12–30
19–44 0–3
13–59 0–54
48.3 ± 17.6 11.9 ± 10.8
21.4 ± 9.2 25.2 ± 3.3
38.3 ± 4.0 6.0 ± 3.6
42.3 ± 9.8 13.0 ± 7.6
3 5 8 10 10 47 68 95 72
2–7 3–10 5–25 7–27 7–29 3–144 18–214 28–99 18–94
11–68 2–33
0–30 20–30
34–42 3–10
29–60 5–32
Minimum-Maximum
42 10 Z = −3.51/P < 0.001 39 5 Z = −1.60/P = 0.027 25 26 Z = −1.95/P = 0.051 51 6 t = 8.43/P < 0.001
Median
Etomidate
3.8 ± 1.4 5.0 ± 2.0 10.8 ± 5.8 12.3 ± 5.9 13.0 ± 6.1 60.6 ± 42.5 79.8 ± 55.8 79.5 ± 24.7 63.1 ± 26.6
Mean ± SD
2–6 3–7 4–14 6–15 7–16 15–79 23–123 13–100 70–98
Minimum-Maximum
36 6 Z = −3.88/P < 0.001 33 2 Z = −2.21/P = 0.027 24 26 Z = −1.66/P = 0.097 45 7 t = 6.53/P < 0.001
Median
Propofol
TABLE 8. Clinical Response and Cognitive Functions
df = 2. *Kruskal-Wallis test. †One-way ANOVA. EMG indicates Electromyography.
Time to spontaneous respiration, min* Time to sufficient respiration, min* Time to opening the eyes, min† Time to Aldrete, min† Time to leave the recovery room, min* EMG duration, s* EEG duration, s† Maximal sustained coherence* PSI*
Propofol
Thiopental
70.4 ± 21.5 20.7 ± 23.6
16.7 ± 11.1 23.5 ± 4.9
42.6 ± 16.5 8.0 ± 11.2
40.9 ± 17.0 12.1 ± 10.6
Mean ± SD
2–9 3–10 5–28 6–30 7–30 17–122 35–148 67–100 9–9.5
38 7 Z = −3.41/P < 0.001 38 4 Z = −2.52/P = 0.012 23 25 Z = −1.66/P = 0.096 75 15 t = 4.66/P = 0.003
27–91 2–67
0–30 14–29
26–80 1–34
10–64 2–35
Minimum-Maximum
Thiopental
5 5 10 10 11 48 82 95 80
Median
4.8 ± 1.9 5.8 ± 2.1 12.2 ± 6.2 13.4 ± 6.9 14.7 ± 8.2 53.9 ± 25.4 90.5 ± 45.8 93.5 ± 8.0 66.7 ± 31.0
2.93 0.48
2.13 0.76
2.29 6.08
0.36 5.30
F/χ2
6.28 3.79 3.87 3.19 2.57 2.73 1.77 2.72 5.93
Mean ± SD Median Minimum-Maximum Mean ± SD Median Minimum-Maximum Mean ± SD Median Minimum-Maximum F/χ2
TABLE 7. Recovery Findings and Seizure Values
0.071 0.625
0.345 0.684
0.318 0.051
0.835 0.071
P
0.043 0.151 0.028 0.050 0.276 0.256 0.182 0.257 0.052
P
Canbek et al Journal of ECT • Volume 31, Number 2, June 2015
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 2, June 2015
observed a better clinical improvement in the propofol group in their study of 96 patients with major depression comparing the effects of propofol and thiopental at baseline and after 6 sessions of ECT. These investigators had included patients with major depression only, who did not take any medications. Ingram et al,29 on the other hand, have reported better clinical improvement with thiopental in their study investigating the effects of thiopental and propofol in 30 patients with depression. They attributed this better clinical improvement to the anticonvulsant feature of propofol. Abdollahi et al23 have found better clinical responses in the etomidate group in their study comparing the effects of thiopental and etomidate in 60 patients with major depression. The absence of any changes in MMSE scores after treatment (evaluated within 24 hours) in the present study shows absence of cognitive deterioration in all 3 groups. Ingram et al29 detected less cognitive adverse effects with thiopental in comparison with propofol. The MMSE score 5 days after the completion of treatment was better with thiopental than that of propofol in the study by Bauer et al26 where patients with depression were investigated. They have commented that this result could be caused by the presence of a difference in the ages of the groups. Maybe the most important limitation of the present study is the inclusion of male patients only, which may prevent generalization of our findings. In conclusion, a similar clinical improvement and similar CVS findings were observed with these 3 anesthetic drugs, without deterioration in cognitive functions. There were no major complications or deaths among this patient series. Our results show that all 3 agents may be used safely in psychiatric male patients without any CVS disorders. Further studies including a larger sample of patients of both sexes are needed. ACKNOWLEDGMENT The authors thank nurses Ahmet Gul, Ali İhsan Seker, Ayla Kardaslar, Cebrail Arslan, Fadime Unal, İklil Ebrisimoglu, Levent Gumus, and Zulfiye Oksuz for their devoted help in the periprocedural measurements in this study as well as Gokhan Ozcan, MD; Gulay Ozakay, MD; Muammer Uye, MD; Hakan Yıldırım, MD; and Ceyhan Oflezer, MD, of the Department of Anesthesiology. The authors also thank Dilek Tunali, MD, and Associate Professor Cigdem Selcukcan Erol, PhD, for reviewing the text and references with a critical eye. REFERENCES 1. Nobler MS, Sackeim HA. Electroconvulsive therapy and transcranial magnetic stimulation. In: Stein DJ, Kupfer DJ, Schatzberg AF, eds. Textbook of Mood Disorders. Washington, DC: American Psychiatric Publishing; 2005:317–329.
Comparison of Propofol, Etomidate, and Thiopental
7. Loosen PT, Beyer JL, Sells SR. Mood disorders. In: Evbert MH, Loosen PT, Nurcombe B, eds. Current Diagnosis and Treatment in Psychiatry. New York, NY: Lange Medical Books/McGraw-Hill; 2000:290–327. 8. Jaffe R. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging: A Task Force Report of the American Psychiatric Association. 2nd ed. Am J Psychiatry. 2002;159:331. 9. Khan A, Mirolo MH, Hughes D, et al. Electroconvulsive therapy. Psychiatr Clin North Am. 1993;16:497–513. 10. Rose CE. Anesthetic and system-based considerations for electroconvulsive therapy. ASA refresh courses in anesthesiol. 2008; 36:143–154. 11. Evlice YE, Tamam L. Electroconvulsive therapy [in Turkish]. In: Koroglu E, Gulec C, eds. Textbook of Psychiatry. Hekimler Yayin Birligi Ankara. 2006:713–725. 12. Başgül E, Celiker V. Anaesthesia in electroconvulsive therapy. Turk J Psychiatry. 2004;15:225–235. 13. Simpson KH, Lynch L. Anaesthesia and electroconvulsive therapy (ECT). Anaesthesia. 1998;53:615–617. 14. Thompson JW, Weiner RD, Myers CP. Use of ECT in the United States in 1975, 1980, and 1986. Am J Psychiatry. 1994;151:1657–1661. 15. Swaim JC, Mansour M, Wydo SM, et al. A retrospective comparison of anesthetic agents in electroconvulsive therapy. J ECT. 2006;22:243–246. 16. Chanpattana W. Anesthesia for ECT. German J Psychiatry. 2001;4:33–39. 17. Rosa MA, Rosa MO, Marcolin MA, et al. Cardiovascular effects of anesthesia in ECT: a randomized, double-blind comparison of etomidate, propofol, and thiopental. J ECT. 2007;23:6–8. 18. Folk JW, Kellner CH, Beale MD, et al. Anesthesia for electroconvulsive therapy: a review. J ECT. 2000;16:157–170. 19. Rosa MA, Rosa MO, Belegarde IM, et al. Recovery after ECT: comparison of propofol, etomidate and thiopental. Rev Bras Psiquiatr. 2008;30:149–151. 20. Gazdag G, Kocsis N, Tolna J, et al. Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia. J ECT. 2004;20:225–229. 21. Murali N, Saravanan ES, Santosh MG, et al. Cardiovascular response to ECT is unaffected by extent of motor seizure modification. Indian J Psychiatry. 1999;41:236–241. 22. Erdil F, Demirbilek S, Begec Z, et al. Effects of propofol or etomidate on QT interval during electroconvulsive therapy. J ECT. 2009;25:174–177. 23. Abdollahi MH, Izadi A, Hajiesmaeili MR, et al. Effect of etomidate versus thiopental on major depressive disorder in electroconvulsive therapy, a randomized double-blind controlled clinical trial. J ECT. 2012;28:10–13. 24. Avramov MN, Husain MM, White PF. The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg. 1995;81:596–602.
2. Stanford AD, Sporn A, Krystal AD. Convulsive and other somatic therapies. In: Gabbard G, ed. Gabbard's Treatments of Psychiatric Disorders. Washington, DC: American Psychiatric Publishing; 2007:449–458.
25. Hooten WM, Rasmussen KG Jr. Effects of general anesthetic agents in adults receiving electroconvulsive therapy: a systematic review. J ECT. 2008;24:208–223.
3. Sackeim HA, Devanand DP, Nobler MS. Electroconvulsive therapy. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven Press; 2000. American College of Neuropsychopharmacology Web site. Available at: http://www.acnp.org/ publications/psycho4generation.aspx. Accessed August 3, 2010.
26. Bauer J, Hageman I, Dam H, et al. Comparison of propofol and thiopental as anesthetic agents for electroconvulsive therapy: a randomized, blinded comparison of seizure duration, stimulus charge, clinical effect, and cognitive side effects. J ECT. 2009;25:85–90.
4. Abrams R. History of electroconvulsive therapy. In: Abrams R, ed. Electroconvulsive Therapy. 4th ed. New York, NY: Oxford University Press; 2002:3–6.
27. Omprakash TM, Ali MI, Anand B, et al. Comparison of thiopentone sodium and propofol in ECT anaesthesia. Indian J Psychol Med. 2008;30:48–51.
5. Ding Z, White PF. Anesthesia for electroconvulsive therapy. Anesth Analg. 2002;94:1351–1364.
28. Purtuloğlu T, Özdemir B, Erdem M, et al. Effect of propofol versus sodium thiopental on electroconvulsive therapy in major depressive disorder: a randomized double-blind controlled clinical trial. J ECT. 2013;29:37–40.
6. Sadock BJ, Sadock VA. Electroconvulsive therapy. In: Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:1117–1123.
29. Ingram A, Schweitzer I, Ng CH, et al. A comparison of propofol and thiopentone use in electroconvulsive therapy: cognitive and efficacy effects. J ECT. 2007;23:158–162.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
97
Comparison of Propofol, Etomidate, and Thiopental in Anesthesia for Electroconvulsive Therapy A Randomized, Double-blind Clinical Trial Ozge Canbek, MD,* Derya Ipekcıoglu, MD,† Okan Oktay Menges, MD,‡ Murat Ilhan Atagun, MD,§ Nesrin Karamustafalıoglu, MD,† Ozlem Zekiye Cetinkaya, MD,† and Mehmet Cem Ilnem, MD† Objectives: This study aimed to compare the effects of propofol, thiopental, and etomidate, which are routinely used in anesthesia for electroconvulsive therapy (ECT), on the cardiovascular system, seizure variables, recovery, cognitive functions, and response to treatment. Methods: Male patients hospitalized at the Seventh Psychiatry Clinics of the Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery who were treated with ECT were investigated prospectively. The effects on cardiovascular system parameters (heart rate, blood pressure, and blood oxygenation), seizure variables (duration and intensity of seizure), and recovery variables were recorded at every session, on prespecified time points, and the findings of the first session were used in this evaluation. In addition, clinical responses to treatment were evaluated with tests of cognitive functions before and after a course of ECT. Adverse effects were recorded. Results: The sociodemographic characteristics of the 3 treatment groups were similar. There were no significant differences among the groups in terms of effects on cardiovascular system variables, seizure variables, and cognitive functions. The clinical response to ECT was good in all groups, without any significant differences. Conclusions: Propofol, etomidate, and thiopental are associated with similar safety and efficacy profiles. Key Words: electroconvulsive therapy, general anesthesia, seizure variables, recovery, adverse effect, clinical efficacy (J ECT 2015;31: 91–97)
E
lectroconvulsive therapy (ECT) dates back to the initial days of modern psychiatry.1–4 Electroconvulsive therapy is indicated in the treatment of major depressive disorder, manic episode, schizophrenic exacerbation, catatonia, and other serious psychiatric disorders.1,5–8 This modality is based on the electrical stimulation of the brain tissues and creation of an epileptic seizure. It was first used by Cerletti and Bini in 1938, after which it became part of the clinical practice.1,5,9–13 It was done without anesthesia until the end of 1940s, after which general anesthetics were started to be used. The technological developments in the last 30 years have increased the efficacy of ECT while decreasing its adverse effects.1,3,5,11,14 Standard ECT application consists of administration of muscle relaxants and anesthetic agents, after which a seizure is induced with an electrical stimulation.15 Successful ECT requires close collaboration between the psychiatrist and the anesthesiologist.16 From the *ECT Center, and †Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery, Istanbul; ‡Faruk Sukan Hospital, Konya and §Department of Psychiatry, School of Medicine, Yildirim Beyazit University, Ankara, Turkey. Received for publication March 17, 2014; accepted August 28, 2014. Reprints: Ozge Canbek, MD, ECT Center, Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery, 34147 Bakırköy, Istanbul, Turkey (e‐mail: [email protected]). The authors have no conflicts of interest or financial disclosures to report. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/YCT.0000000000000190
An anesthetic agent with a rapid onset and short duration of action and with a minimal effect on the threshold and duration of seizures as well as hemodynamic parameters, which enables recovery in a short time, is searched for a safe, comfortable anesthesia, with few adverse effects and no effects on the psychiatric treatment. The more comfortable the treatment, the better will be the patient’s compliance and satisfaction. The most frequently used anesthesiologic agents are methohexital, thiopental, etomidate, propofol, ketamine, and sevoflurane. Methohexital, which is considered as the criterion standard, is an effective and cheap anesthetic agent with a fast onset of action, minimal anticonvulsant activity, and a fast recovery.5,8,15,17,18 This agent is not present in Turkey, and routinely used anesthetic agents are propofol, etomidate, and thiopental. Propofol is a fast-acting, nonbarbiturate anesthetic agent with antihypertensive properties, which has the negative features of increasing the seizure threshold and shortening seizure duration. Etomidate is a nonbarbiturate imidazolic derivative. Its effect and metabolism are rapid, and it has a minimal effect on the seizure threshold and cardiovascular system. Its main disadvantages are myoclonus and pain at the injection site. Thiopental is a barbiturate anesthetic agent with characteristics similar to methohexital. Sinus bradycardia and premature ventricular beats are more frequently seen with this medication.5,17,19,20 We aimed to compare the effects of 3 anesthetic agents (propofol, etomidate, and thiopental) that are routinely used in ECT anesthesia on the cardiovascular system, seizure, recovery, cognitive functions, and response to treatment in a prospective, double-blind study.
MATERIALS AND METHODS Patients The patients were male patients hospitalized at the Male Patient Ward of Seventh Psychiatry Clinics of Bakırköy Teaching Hospital for Psychiatry, Neurology, and Neurosurgery, in whom treatment with ECT was deemed necessary. The psychiatric diagnoses of these patients are presented in Table 1. A total of 56 patients aged between 20 and 60 years who did not have a previously diagnosed cardiovascular disorder were included, between August 2010 and May 2011, and 51 patients completed the study. The patients were randomized to 3 groups, in which 1 anesthetic agent was used in all sessions. The effects on cardiovascular system parameters (heart rate [HR], blood pressure, and blood oxygenation), seizure variables (the duration and intensity of seizure), and recovery variables were recorded at every session on prespecified time points. The findings of the first ECT session were used in the evaluation. Adverse effects were recorded. In addition, clinical responses to treatment were evaluated with tests of cognitive functions before and after a course of ECT.
Journal of ECT • Volume 31, Number 2, June 2015
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
91
Journal of ECT • Volume 31, Number 2, June 2015
Canbek et al
TABLE 1. The Distribution of Diagnoses in the 3 Groups Propofol, n (%) Unipolar depression Bipolar affective disorder, mania Schizophrenia Schizoaffective disorder Atypical psychosis Total
Etomidate, n (%)
Thiopental, n (%)
— 4 (25)
5 (25) 6 (30) 8 (40) 1 (5) — 20 (39.21)
— 7 (47)
9 (56) — 3 (19) 16 (31.37)
6 (40) — 2 (13) 15 (29.41)
We used a double-blind design, where the patients, anesthesiologists, and raters were blinded in terms of the anesthetic agent. One anesthesiologist (unblinded) administered anesthesia at all sessions and remained as an observer in case of emergencies, whereas another anesthesiologist and a nurse (who were blinded) recorded all seizure and anesthesia parameters. The patients were informed about the study, and written informed consents were obtained from the patients and/or their relatives/representatives. In addition, approval from the institutional ethics committee was obtained. The study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice.
Assessments All patients were thoroughly evaluated before entering the study, which included physical examination by a physician and an anesthesiologist. Patients with any cardiovascular disorder (including arterial hypertension) were excluded. No patients were taking any antihypertensive medications. All patients were class I to II according to American Society of Anesthesiologists (ASA) criteria (50 [98.03%] patients were ASA I and 1 [1.97%] patient was ASA II. The decisions on diagnosis and ECT indications were given by the patients’ attending psychiatrists. At least 5 sessions (range, 5–14) were applied to all patients, who were considered acceptable for evaluation of clinical response. Mini-Mental State Examination (MMSE) was applied to the patients 1 day before the first ECT session and 1 day after the last ECT session. Clinical response to treatment was evaluated as “no response,” “partial response,” and “good response” and additional psychiatric scales were used for evaluation. Brief Psychiatric Rating Scale (BPRS) was used in all patients, Scale for the Assessment of Positive Symptoms (SAPS) was used in patients with psychotic disorder, Young Mania Rating Scale (YMRS) was used in patients with mania, and Hamilton Depression Rating Scale was used in patients with depression. The last ECT session was decided by the treating psychiatrist. When no clinically significant changes were observed after 2
consequent sessions, ECT treatment was ended. The numbers of sessions and responses to treatment are presented in Table 2. Two patients were excluded because of withdrawal of informed consent, 1 patient left the hospital without permission, 1 patient was excluded because of a change of anesthetic agent, and 1 patient was excluded because of premature termination of therapy due to prolonged (>24 hours) bradycardia, which occurred after the first session. Among the excluded patients, 3 patients were on propofol, 1 patient was on etomidate, and 1 patient was on thiopental.
Concomitant Medications All patients were taking combinations of psychotropic medications at maximally tolerated doses, without clinical improvement, and ECT treatment was considered necessary by their attending psychiatrists. Thus, their usual psychopharmacological therapy continued during the course of study. The medications of the patients are presented in Table 3. The pharmacotherapy of the patients was not changed or restricted in any way in accordance with the protocol of this study. The total number of patients is not adequate for a comparison of the effects of different pharmacoactive medications on the response to ECT.
ECT PROCEDURE Bitemporofrontal ECT was administered with a Thymatron IV device (Somatics Inc, Lake Bluff, Ill) at the ECT center of Bakırköy, 3 times a week, every other day, in the morning. The patients were fasted for 6 hours before the procedure. The ECT application electrodes were bilaterally placed at the temporofrontal regions, whereas ECT recording electrodes were placed at the frontal and mastoid regions. Baseline systolic blood pressure (SBP) and diastolic blood pressure (DBP), HR, as well as body temperature were measured and recorded before ECT. Ventilation was maintained with a mask. Pulse oximeter (Nonin 2500A pulse oximeter) was placed at the index fingers of the patients, and oxygen saturation was monitored. Stimulus dosage was adjusted in accordance with “half-age method.” Seizures shorter than 20 seconds were considered inadequate, and the stimulation dose was increased 50%, with a maximum of 3 times in a session. Additional anesthetics or muscle relaxants were not required.
Anesthetic Medications The dose of propofol was 0.75 to 1.0 mg/kg, the dose of etomidate was 0.15 to 0.25 mg/kg, and the dose of thiopental was 1.5 to 2.5 mg/kg. The dose of muscle relaxant (ie, succinylcholine) was 0.5 mg/kg. The anesthetic was selected in accordance with a randomization table. A total of 20 (39.22%) patients were TABLE 3. Medications That Were Used by the Patients During the Study Propofol Etomidate Thiopental
TABLE 2. The Distribution of Responses to Treatment of Patients According to Number of Sessions n
Good response Partial response No response
5
6
7
8
9
10
11
12
14
2 — —
3 1 —
11 4 —
6 2 —
6 1 2
4 2 —
1 2 —
2 — 1
— 1 —
n indicates number of session.
92
www.ectjournal.com
Haloperidol Haloperidol + quetiapine Haloperidol + chlorpromazine Haloperidol + quetiapine + zuclopenthixole Haloperidol + venlafaxine Haloperidol + olanzapine Quetiapine + mirtazapine + sertraline Total
2 12 3 2
2 9 1 1
— 13 1 —
1 — —
— 2 —
— 1 1
20
15
16
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 2, June 2015
5 8 40
1–15 5–12 30–60
2.56 1.39 8.54 1.52 2.14 0.83 0.91 0.25 2.36 21–40 60–90 5–11 29 70 5
4 8 40
1–22 5–14 30–60
29.1 ± 4.7 71.3 ± 8.2 6.5 ± 2.2 2 (13.3) 13 (86.7) 7 (46.7) 4.9 ± 3.6 8.1 ± 1.7 39.3 ± 8.8 22–49 55–100 5–15 32 80 8
3 8 40
1–25 6–12 30–60
33.9 ± 9.0 78.3 ± 11.5 8.9 ± 3.7 3 (18.8) 12 (75) 8 (50) 6.6 ± 6.6 8.6 ± 2.5 42.5 ± 7.7 23–58 48–102 5–15 34 69 7
Mean ± SD/n (%) Minimum-Maximum Median
Propofol
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
df = 2. *One-way ANOVA. †Kruskal-Wallis test. ‡χ2 test.
A total of 56 patients were included in this study, and 51 patients completed the study. The sociodemographic and clinical characteristics of the patients are summarized in Table 4. The psychiatric diagnoses of the patients in this series were unipolar major depression in 5 (9.80%) patients (with psychotic features except 1 patient), bipolar disorder (manic episode) in 17 (33.33%) patients, schizophrenia in 23 (45%) patients, schizoaffective disorder in 1 (1.96%) patient, and atypical psychosis in 5 (9.80%) patients. The indications for ECT were as follows: unresponsiveness to other therapies in 16 patients, risk for suicide in 5 patients, risk for homicide in 7 patients, risk for suicide and
35.0 ± 8.9 73.6 ± 14.4 7.9 ± 3.1 6 (30) 13 (65) 8 (40) 4.2 ± 5.3 8.4 ± 1.6 39.0 ± 7.9
Sociodemographic and Clinical Characteristics
Mean ± SD/n (%)
RESULTS
TABLE 4. Sociodemographic and Clinical Characteristics
The results of the first session were used for the statistical analysis of cardiovascular, recovery, and seizure findings. Means, SDs, medians, minimal/maximal values, rates, and frequencies were used in the descriptive statistics. A P value of less than 0.05 was accepted as statistically significant. The KolmogorovSmirnov test was performed to examine the distribution characteristics of the variables. According to distribution characteristics, continuous variables were compared with repeated-measures analysis of variance (ANOVA), 1-way ANOVA, and Kruskal-Wallis tests. The Tukey test was performed for post hoc comparisons. Cardiovascular results were compared with repeated-measures ANOVA. Response to treatments as measured using the YMRS, the BPRS, and the SAPS was compared with the Kruskal-Wallis test and the ANOVA. In the ANOVAs and the Kruskal-Wallis tests, the dependent variables were anesthetic groups. Paired samples t test and Wilcoxon test were used for intragroup comparisons between measurements done before and after session. The χ2 test was used to compare categorical variables. Details of the tests are presented in the footnotes of the tables. Statistical Package for the Social Sciences version 22.0 software was used in the statistical analysis.
Etomidate
Statistical Analysis
Median
Electroencephalogram (EEG) was automatically recorded using a Thymatron IV device. Electroencephalographic duration, HR (baseline and peak), seizure energy index, seizure concordance index, and postictal suppression index (PSI) were calculated using the ECT device. The duration of seizure in EEG was detected using the device and also observed by the investigators. Motor seizure activity was observed and measured with a chronometer. The seizure intensity was evaluated on a scale of 1 to 5.21
Minimum-Maximum
Mean ± SD/n (%)
Electrophysiologic Evaluation
Age, y* Weight, kg* Duration of education, y† Marital status (married)‡ Nicotine addiction‡ History of ECT‡ No. days in hospital* No. sessions* Dose of succinylcholine, IU*
Thiopental
The duration of anesthesia was recorded with a chronometer, starting with administration of anesthetic and time to spontaneous breathing, sufficient breathing, and opening of the eyes in response to verbal instructions; the modified Aldrete score and time to leave the recovery room were also recorded.
Median
Recovery Findings
Minimum-Maximum
F/χ2
P
anesthetized with propofol; 16 (31.37%), with etomidate; and 15 (29.41%), with thiopental. Cardiovascular effects were assessed through monitoring the SBP and DBP levels as well as HR with a noninvasive digital monitor (Braun BP4000). Measurements were recorded at 7 time points: preparation, anesthesia induction, seizure, postictal first minute, postictal fifth minute, postictal 10th minute, and postictal 30th minute.
0.088 0.259 0.603 0.468 0.346 0.380 0.411 0.783 0.307
Comparison of Propofol, Etomidate, and Thiopental
www.ectjournal.com
93
Journal of ECT • Volume 31, Number 2, June 2015
Canbek et al
homicide in 2 patients, catatonia in 2 patients, excitation in 1 patient, excitation and unresponsiveness in 3 patients, risk for homicide and excitation in 6 patients, as well as risk for homicide and unresponsiveness in 9 patients. The distribution of adverse effects in the 3 groups is presented in Table 5. There were no differences among the anesthetic agents in terms of adverse effects. All adverse effects resolved spontaneously. There were no major complications or death during or after ECT.
Cardiovascular System Findings All of the cardiovascular system (CVS) variables of the first ECT session are presented in Table 6. Heart rate showed a significant increase in the seizure period in comparison with the preparation period in all 3 groups, without any significant intergroup differences. The SBP showed a significant increase during the seizure in comparison with the preparation period in all 3 groups, also without any significant intergroup differences. Systolic blood pressure was significantly lower at the 30’ postictal evaluation in comparison with the preparation period in the propofol group, whereas there were no significant differences between the 30’ postictal evaluation and the preparation period in the etomidate and thiopental groups. The DBP showed a significant increase during the seizure in comparison with the preparation period in all 3 groups, without any significant intergroup differences.
Seizure Variables Seizure variables are presented in Table 7. Motor and EEG seizure, maximum sustained coherence, and PSI did not show a significant difference among the 3 groups.
Recovery Variables Recovery variables are presented in Table 7. Spontaneous respiration returned earlier in the propofol group in comparison with the thiopental group. Time to opening the eyes was significantly shorter in the propofol group in comparison with the thiopental group. There were no significant differences among the propofol, etomidate, and thiopental groups in terms of time to TABLE 5. The Distribution of Adverse Effects Anesthetic Agents Adverse Effect Hypertension Bradycardia Tachycardia Prolonged seizure >120 s Confusion Excitation Amnesia Muscle-joint pain Hypersalivation Late recovery
Propofol (n = 20)
Etomidate (n = 16)
Thiopental (n = 15)
1 0 1 1 1 2 1 0 2 1 10
1 2 0 1 2 0 0 2 2 0 10
0 0 1 4 3 0 0 0 1 0 9
Adverse effects were observed in 10 (50%) patients of the propofol group, 10 (62.5%) patients of the etomidate group, and 9 (60%) patients of the thiopental group (χ2 = 0.65, P = 0.722).
94
www.ectjournal.com
sufficient respiration, time to Aldrete of higher than 9, and time to leave the room.
Clinical Responses and Cognitive Functions Clinical responses and cognitive functions are presented in Table 8. The posttreatment BPRS, SAPS, and YMRS values showed a significant decrease in comparison with the pretreatment values in all 3 groups, without any significant differences among groups. The pretreatment MMSE values and posttreatment MMSE values in 3 groups did not show significant differences.
DISCUSSION In this study comparing the effects of 3 frequently used anesthetic agents in ECT on recovery, cardiovascular variables, cognitive functions, and response to treatment, the only significant differences among the agents are lower SBP with propofol in the 30' postictal measurement and shorter time to spontaneous respiration and time to opening the eyes with propofol. Except these, there were no significant differences among the groups in other cardiovascular system findings. Erdil et al22 have observed a more stable hemodynamic response with propofol in comparison with etomidate in their study evaluating patients with major depressive disorder and recommended the use of this agent in ECT anesthesia. Gazdag et al20 have found better hemodynamic effects of propofol in comparison with etomidate in their study comparing etomidate and propofol in patients with schizophrenia and depression. The differences between studies may be caused by different characteristics (age, diagnosis, etc) of the patient populations. The propofol group recovered faster than the other 2 groups in our study. Rosa et al17,19 have detected similar effects with propofol in their studies comparing etomidate, propofol, and thiopental in patients with major depression. No differences were found between recovery findings with etomidate and thiopental in the study by Abdollahi et al,23 whereas the longest recovery period was observed with etomidate by Avramov et al.24 Hooten and Rasmussen25 evaluated 41 studies investigating 14 anesthetic agents and found that the recovery periods were longer with anesthetic agents with longer seizure durations but did not find any significant differences among the anesthetic agents in terms of recovery. There were no intergroup differences in the EEG and motor seizure durations in our study. Bauer et al26 have found that the duration of seizure was significantly shorter with propofol, but this did not cause a difference in clinical improvement in their study comparing propofol and thiopental in patients with depression. Omprakash et al27 also found similar seizure features. Generally, the duration of seizure was longer with etomidate in many studies.15,24 Gazdag et al20 found longer motor and EEG seizures with etomidate in their study comparing etomidate and propofol in patients with schizophrenia and depression. Avramov et al24 have found that the duration of seizure did not decrease in a dosedependent fashion with etomidate in their study comparing methohexital, etomidate, and propofol. Hooten and Rasmussen25 had found the longest seizure durations with methohexital. The most frequent adverse effects were prolonged seizure, early confusion, and hypersalivation. Omprakash et al27 have reported that, among the most frequently seen adverse effects, arrhythmias and nausea occurred more frequently in patients who were given thiopental and that pain at the injection site was more frequent in patients who were given propofol. One of the most important findings in the present study is the good response to treatment in all groups. Purtuloğlu et al28 had © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation Peak HR Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation SBP Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation DBP Preparation Induction Seizure Postictal 1’ Postictal 5’ Postictal 10’ Postictal 30’ Change with preparation
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Propofol
Median Minimum-Maximum
96.9 ± 2.3 98 92–100 97.6 ± 2.4 98 92–100 98.9 ± 1.4 99 94–100 97.2 ± 3.6 99 86–100 93.6 ± 3.4 94 86–98 93.6 ± 3.0 94 86–98 95.0 ± 2.7 96 88–98 df = 6/F = 17.81/P < 0.001 90.4 ± 18.9 87 66–139 95.6 ± 20.0 94 67–146 110.9 ± 38.0 96 61–180 91.6 ± 20.0 84 67–123 90.6 ± 17.3 92 59–124 93.9 ± 20.7 92 65–127 89.8 86 68–126 df = 6/F = 4.14/P = 0.029 124.1 ± 18.3 122 69–158 129.2 ± 24.8 125 97–182 164.1 ± 45.2 154 86–259 136.9 ± 29.0 136 87–204 123.7 ± 25.4 123 77–177 115.6 ± 16.6 115 98–159 117.6 ± 16.5 118 84–146 df = 6/F = 9.77/P < 0.001 76.8 ± 12.4 74 45–105 84.8 ± 14.9 84 49–106 94.3 ± 23.1 93 63–150 77.1 ± 16.1 76 50–108 75.0 ± 19.7 70 41–106 69.2 ± 14.2 70 43–91 72.6 ± 15.8 71 49–104 df = 6/F = 8.56/P < 0.001
Repeated-measures ANOVA.
SPO2
Mean ± SD
TABLE 6. Cardiovascular Findings Etomidate Median Minimum-Maximum
96.8 ± 1.3 97 95–99 98.3 ± 1.5 99 96–100 98.8 ± 2.4 99 90–100 97.3 ± 1.6 98 94–99 94.1 ± 3.8 95 85–99 93.1 ± 3.1 94 87–99 94.3 ± 2.7 95 88–97 df = 6/F = 15.99/P < 0.001 83.2 ± 14.3 80 63–115 98.3 ± 18.5 104 61–126 122.8 ± 52.0 126 49–196 87.1 ± 25.6 78 57–157 88.4 ± 12.4 88 58–108 91.0 ± 15.1 96 57–115 87.8 ± 18.7 91 53–120 df = 6/F = 4.80/P = 0.016 126.6 ± 20.2 120 99–165 137.3 ± 20.0 135 103–180 195.1 ± 44.4 187 120–268 141.4 ± 19.0 139 110–197 126.4 ± 14.9 124 107–153 120.6 ± 14.3 116 103–145 126.2 ± 23.3 122 101–192 df = 6/F = 16.48/P < 0.001 77.0 ± 13.3 75 60–103 90.8 ± 12.8 96 70–106 99.1 ± 22.4 105 50–146 82.5 ± 17.3 81 50–106 72.8 ± 15.0 71 43–105 69.1 ± 17.2 72 45–105 76.9 ± 18.0 73 47–106 df = 6/F = 8.17/P < 0.001
Mean ± SD
Thiopental Median Minimum-Maximum
96.5 ± 2.2 96 91–99 98.7 ± 0.8 99 97–100 98.2 ± 2.5 99 90–100 98.1 ± 2.0 99 93–100 94.9 ± 4.8 97 84–100 94.7 ± 3.5 96 88–99 93.8 ± 3.4 94 87–98 df = 6/F = 17.81/P < 0.001 80.7 ± 16.3 81 54–110 96.1 ± 15.6 95 71–124 99.9 ± 34.2 94 52–160 88.9 ± 21.3 93 53–130 90.5 ± 17.1 93 63–115 87.3 ± 16.0 83 67–120 84.6 ± 15.3 80 64–117 df = 6/F = 2.69/P = 0.079 126.7 ± 19.1 124 102–179 133.3 ± 21.5 134 103–182 178.8 ± 42.5 179 121–252 137.2 ± 22.2 131 110–180 117.9 ± 22.3 117 86–170 112.2 ± 12.8 109 97–135 109.7 ± 13.8 110 93–138 df = 6/F = 8.06/P < 0.001 75.6 ± 12.1 75 57–105 88.1 ± 10.3 87 70–104 105.3 ± 28.4 100 68–149 82.7 ± 12.2 81 64–105 69.4 ± 16.3 71 50–104 68.1 ± 10.4 65 56–92 63.8 ± 7.6 60 55–82 df = 6/F = 4.51/P < 0.001
Mean ± SD
0.356
P
0.266
0.361
1.27
1.13
0.727 0.720
1.12
F/χ2
Journal of ECT • Volume 31, Number 2, June 2015 Comparison of Propofol, Etomidate, and Thiopental
www.ectjournal.com
95
96
www.ectjournal.com
3.2 ± 0.9 4.4 ± 1.2 7.7 ± 2.8 9.1 ± 2.5 9.9 ± 2.4 41.8 ± 17.0 62.6 ± 31.6 90.7 ± 19.5 85.6 ± 9.3
3 4 7 9 9 40 53 96 87
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
df = 2. *Kruskal-Wallis test. †Wilcoxon t test. ‡One-way ANOVA. §Paired samples.
Before treatment After treatment Before/after change† YMRS* Before treatment After treatment Before/after change† MMSE* Before treatment After treatment Before/after change† SAPS‡ Before treatment After treatment Before/after change§
BPRS*
48.7 ± 23.9 16.8 ± 23.6
17.2 ± 12.0 24.8 ± 4.2
32.5 ± 8.1 1.5 ± 1.2
39.3 ± 12.7 9.6 ± 12.6
Mean ± SD
Etomidate
11–83 0–70
0–30 12–30
19–44 0–3
13–59 0–54
48.3 ± 17.6 11.9 ± 10.8
21.4 ± 9.2 25.2 ± 3.3
38.3 ± 4.0 6.0 ± 3.6
42.3 ± 9.8 13.0 ± 7.6
3 5 8 10 10 47 68 95 72
2–7 3–10 5–25 7–27 7–29 3–144 18–214 28–99 18–94
11–68 2–33
0–30 20–30
34–42 3–10
29–60 5–32
Minimum-Maximum
42 10 Z = −3.51/P < 0.001 39 5 Z = −1.60/P = 0.027 25 26 Z = −1.95/P = 0.051 51 6 t = 8.43/P < 0.001
Median
Etomidate
3.8 ± 1.4 5.0 ± 2.0 10.8 ± 5.8 12.3 ± 5.9 13.0 ± 6.1 60.6 ± 42.5 79.8 ± 55.8 79.5 ± 24.7 63.1 ± 26.6
Mean ± SD
2–6 3–7 4–14 6–15 7–16 15–79 23–123 13–100 70–98
Minimum-Maximum
36 6 Z = −3.88/P < 0.001 33 2 Z = −2.21/P = 0.027 24 26 Z = −1.66/P = 0.097 45 7 t = 6.53/P < 0.001
Median
Propofol
TABLE 8. Clinical Response and Cognitive Functions
df = 2. *Kruskal-Wallis test. †One-way ANOVA. EMG indicates Electromyography.
Time to spontaneous respiration, min* Time to sufficient respiration, min* Time to opening the eyes, min† Time to Aldrete, min† Time to leave the recovery room, min* EMG duration, s* EEG duration, s† Maximal sustained coherence* PSI*
Propofol
Thiopental
70.4 ± 21.5 20.7 ± 23.6
16.7 ± 11.1 23.5 ± 4.9
42.6 ± 16.5 8.0 ± 11.2
40.9 ± 17.0 12.1 ± 10.6
Mean ± SD
2–9 3–10 5–28 6–30 7–30 17–122 35–148 67–100 9–9.5
38 7 Z = −3.41/P < 0.001 38 4 Z = −2.52/P = 0.012 23 25 Z = −1.66/P = 0.096 75 15 t = 4.66/P = 0.003
27–91 2–67
0–30 14–29
26–80 1–34
10–64 2–35
Minimum-Maximum
Thiopental
5 5 10 10 11 48 82 95 80
Median
4.8 ± 1.9 5.8 ± 2.1 12.2 ± 6.2 13.4 ± 6.9 14.7 ± 8.2 53.9 ± 25.4 90.5 ± 45.8 93.5 ± 8.0 66.7 ± 31.0
2.93 0.48
2.13 0.76
2.29 6.08
0.36 5.30
F/χ2
6.28 3.79 3.87 3.19 2.57 2.73 1.77 2.72 5.93
Mean ± SD Median Minimum-Maximum Mean ± SD Median Minimum-Maximum Mean ± SD Median Minimum-Maximum F/χ2
TABLE 7. Recovery Findings and Seizure Values
0.071 0.625
0.345 0.684
0.318 0.051
0.835 0.071
P
0.043 0.151 0.028 0.050 0.276 0.256 0.182 0.257 0.052
P
Canbek et al Journal of ECT • Volume 31, Number 2, June 2015
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Journal of ECT • Volume 31, Number 2, June 2015
observed a better clinical improvement in the propofol group in their study of 96 patients with major depression comparing the effects of propofol and thiopental at baseline and after 6 sessions of ECT. These investigators had included patients with major depression only, who did not take any medications. Ingram et al,29 on the other hand, have reported better clinical improvement with thiopental in their study investigating the effects of thiopental and propofol in 30 patients with depression. They attributed this better clinical improvement to the anticonvulsant feature of propofol. Abdollahi et al23 have found better clinical responses in the etomidate group in their study comparing the effects of thiopental and etomidate in 60 patients with major depression. The absence of any changes in MMSE scores after treatment (evaluated within 24 hours) in the present study shows absence of cognitive deterioration in all 3 groups. Ingram et al29 detected less cognitive adverse effects with thiopental in comparison with propofol. The MMSE score 5 days after the completion of treatment was better with thiopental than that of propofol in the study by Bauer et al26 where patients with depression were investigated. They have commented that this result could be caused by the presence of a difference in the ages of the groups. Maybe the most important limitation of the present study is the inclusion of male patients only, which may prevent generalization of our findings. In conclusion, a similar clinical improvement and similar CVS findings were observed with these 3 anesthetic drugs, without deterioration in cognitive functions. There were no major complications or deaths among this patient series. Our results show that all 3 agents may be used safely in psychiatric male patients without any CVS disorders. Further studies including a larger sample of patients of both sexes are needed. ACKNOWLEDGMENT The authors thank nurses Ahmet Gul, Ali İhsan Seker, Ayla Kardaslar, Cebrail Arslan, Fadime Unal, İklil Ebrisimoglu, Levent Gumus, and Zulfiye Oksuz for their devoted help in the periprocedural measurements in this study as well as Gokhan Ozcan, MD; Gulay Ozakay, MD; Muammer Uye, MD; Hakan Yıldırım, MD; and Ceyhan Oflezer, MD, of the Department of Anesthesiology. The authors also thank Dilek Tunali, MD, and Associate Professor Cigdem Selcukcan Erol, PhD, for reviewing the text and references with a critical eye. REFERENCES 1. Nobler MS, Sackeim HA. Electroconvulsive therapy and transcranial magnetic stimulation. In: Stein DJ, Kupfer DJ, Schatzberg AF, eds. Textbook of Mood Disorders. Washington, DC: American Psychiatric Publishing; 2005:317–329.
Comparison of Propofol, Etomidate, and Thiopental
7. Loosen PT, Beyer JL, Sells SR. Mood disorders. In: Evbert MH, Loosen PT, Nurcombe B, eds. Current Diagnosis and Treatment in Psychiatry. New York, NY: Lange Medical Books/McGraw-Hill; 2000:290–327. 8. Jaffe R. The Practice of Electroconvulsive Therapy: Recommendations for Treatment, Training, and Privileging: A Task Force Report of the American Psychiatric Association. 2nd ed. Am J Psychiatry. 2002;159:331. 9. Khan A, Mirolo MH, Hughes D, et al. Electroconvulsive therapy. Psychiatr Clin North Am. 1993;16:497–513. 10. Rose CE. Anesthetic and system-based considerations for electroconvulsive therapy. ASA refresh courses in anesthesiol. 2008; 36:143–154. 11. Evlice YE, Tamam L. Electroconvulsive therapy [in Turkish]. In: Koroglu E, Gulec C, eds. Textbook of Psychiatry. Hekimler Yayin Birligi Ankara. 2006:713–725. 12. Başgül E, Celiker V. Anaesthesia in electroconvulsive therapy. Turk J Psychiatry. 2004;15:225–235. 13. Simpson KH, Lynch L. Anaesthesia and electroconvulsive therapy (ECT). Anaesthesia. 1998;53:615–617. 14. Thompson JW, Weiner RD, Myers CP. Use of ECT in the United States in 1975, 1980, and 1986. Am J Psychiatry. 1994;151:1657–1661. 15. Swaim JC, Mansour M, Wydo SM, et al. A retrospective comparison of anesthetic agents in electroconvulsive therapy. J ECT. 2006;22:243–246. 16. Chanpattana W. Anesthesia for ECT. German J Psychiatry. 2001;4:33–39. 17. Rosa MA, Rosa MO, Marcolin MA, et al. Cardiovascular effects of anesthesia in ECT: a randomized, double-blind comparison of etomidate, propofol, and thiopental. J ECT. 2007;23:6–8. 18. Folk JW, Kellner CH, Beale MD, et al. Anesthesia for electroconvulsive therapy: a review. J ECT. 2000;16:157–170. 19. Rosa MA, Rosa MO, Belegarde IM, et al. Recovery after ECT: comparison of propofol, etomidate and thiopental. Rev Bras Psiquiatr. 2008;30:149–151. 20. Gazdag G, Kocsis N, Tolna J, et al. Etomidate versus propofol for electroconvulsive therapy in patients with schizophrenia. J ECT. 2004;20:225–229. 21. Murali N, Saravanan ES, Santosh MG, et al. Cardiovascular response to ECT is unaffected by extent of motor seizure modification. Indian J Psychiatry. 1999;41:236–241. 22. Erdil F, Demirbilek S, Begec Z, et al. Effects of propofol or etomidate on QT interval during electroconvulsive therapy. J ECT. 2009;25:174–177. 23. Abdollahi MH, Izadi A, Hajiesmaeili MR, et al. Effect of etomidate versus thiopental on major depressive disorder in electroconvulsive therapy, a randomized double-blind controlled clinical trial. J ECT. 2012;28:10–13. 24. Avramov MN, Husain MM, White PF. The comparative effects of methohexital, propofol, and etomidate for electroconvulsive therapy. Anesth Analg. 1995;81:596–602.
2. Stanford AD, Sporn A, Krystal AD. Convulsive and other somatic therapies. In: Gabbard G, ed. Gabbard's Treatments of Psychiatric Disorders. Washington, DC: American Psychiatric Publishing; 2007:449–458.
25. Hooten WM, Rasmussen KG Jr. Effects of general anesthetic agents in adults receiving electroconvulsive therapy: a systematic review. J ECT. 2008;24:208–223.
3. Sackeim HA, Devanand DP, Nobler MS. Electroconvulsive therapy. In: Bloom FE, Kupfer DJ, eds. Psychopharmacology: The Fourth Generation of Progress. New York, NY: Raven Press; 2000. American College of Neuropsychopharmacology Web site. Available at: http://www.acnp.org/ publications/psycho4generation.aspx. Accessed August 3, 2010.
26. Bauer J, Hageman I, Dam H, et al. Comparison of propofol and thiopental as anesthetic agents for electroconvulsive therapy: a randomized, blinded comparison of seizure duration, stimulus charge, clinical effect, and cognitive side effects. J ECT. 2009;25:85–90.
4. Abrams R. History of electroconvulsive therapy. In: Abrams R, ed. Electroconvulsive Therapy. 4th ed. New York, NY: Oxford University Press; 2002:3–6.
27. Omprakash TM, Ali MI, Anand B, et al. Comparison of thiopentone sodium and propofol in ECT anaesthesia. Indian J Psychol Med. 2008;30:48–51.
5. Ding Z, White PF. Anesthesia for electroconvulsive therapy. Anesth Analg. 2002;94:1351–1364.
28. Purtuloğlu T, Özdemir B, Erdem M, et al. Effect of propofol versus sodium thiopental on electroconvulsive therapy in major depressive disorder: a randomized double-blind controlled clinical trial. J ECT. 2013;29:37–40.
6. Sadock BJ, Sadock VA. Electroconvulsive therapy. In: Kaplan and Sadock’s Synopsis of Psychiatry: Behavioral Sciences/Clinical Psychiatry. Philadelphia, PA: Lippincott Williams & Wilkins; 2007:1117–1123.
29. Ingram A, Schweitzer I, Ng CH, et al. A comparison of propofol and thiopentone use in electroconvulsive therapy: cognitive and efficacy effects. J ECT. 2007;23:158–162.
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
www.ectjournal.com
97
