ORIGINAL ARTICLE
A Retrospective Comparison of Anesthetic Agents
in Electroconvulsive Therapy
Jennifer C. Swaim, PhD,*Þ Maher Mansour, MD,*Þ Salina M. Wydo, BS,* and Jeffrey L. Moore, MD*Þ
Abstract: A recent lack of availability of the anesthetic agent
methohexital in the United States allowed for a naturalistic study of
the efficacy and the adverse effects of alternatives. Methohexital,
propofol, and thiopental were compared as anesthetic agents for
electroconvulsive therapy in 95 patients treated during a 23-month
period in a general public hospital. Missed seizures and arrhythmias
were infrequently observed (G4% for any agent). Methohexital was
found significantly related to longer seizure durations in comparison
with both other agents (P G 0.01). The use of propofol was associated
with increased risk of missed seizure (8.9%) compared with
methohexital (3.9%) and thiopental (3.2%). Propofol was also
associated with higher doses of administered energy, with a
statistically significant difference (P = 0.018) observed between
propofol and thiopental. Although propofol required the greatest
energy delivery, it was associated with the shortest seizure durations.
Methohexital resulted in the longest seizure duration, and thiopental
was associated with the least amount of energy delivery with an
intermediate seizure length.
Key Words: anesthetics, electroconvulsive therapy, methohexital,
propofol, thiopental
(J ECT 2006;22:243Y246)
T he standard procedure for electroconvulsive therapy
(ECT) involves the administration of muscle-relaxing
and anesthetic agents, followed by the administration of an
electric stimulus capable of inducing electroencephalo-
graphic (EEG) seizure.1 The ideal anesthetic agent for ECT
would have a rapid onset and short duration of action without
compromising the efficacy of the seizure treatment.2 The
American Psychiatric Association recommends methohexital
as an anesthetic agent because of its established safety record,
effectiveness, and low cost1; however, it became unavailable
in August 2002 because of nationwide recall and manufactur-
ing delays (King Pharmaceuticals, personal communication,
August 4, 20053), forcing a switch to alternative agents and
providing a naturalistic opportunity for a comparison of their
effectiveness. Propofol, ketamine, sevoflurane, etomidate,
From the *Akron General Medical Center, Department of Psychiatry and
Behavioral Sciences, Akron, OH; and the †Northeastern Ohio Uni-
versities College of Medicine, Rootstown, OH.
Received for publication April 4, 2006; accepted August 20, 2006.
Reprints: Jennifer Swaim, PhD, Akron General Medical Center, Department
of Psychiatry and Behavioral Sciences, 4th Floor, Ambulatory Care
Center, 400 Wabash Avenue, Akron, OH 44307-2433 (e-mail: jswaim@
agmc.org).
Copyright * 2006 by Lippincott Williams & Wilkins
J ECT & Volume 22, Number 4, December 2006
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andVmost commonlyVthiopental have been used in place of
methohexital. Their use has prompted renewed interest in
the safety, efficacy, and adverse effects of these medications
for ECT.
Ketamine remains largely unused because of the
general, if contested, belief that it has unpleasant hallucino-
genic adverse effects, and that it may exacerbate psychotic
symptoms.4 Seroflurane’s use is limited to special situations
requiring an inhalational agent. Etomidate, although advan-
tageous because of its ability to decrease seizure threshold
(thus reducing energy delivery and cognitive adverse
effects5), is considerably more expensive than other agents.
In addition, it may briefly exacerbate anxiety levels while
taking effect.
Only 2 of the alternative agents have been routinely
used at the Akron General Medical Center: propofol and
thiopental. Both alternative anesthetics have been reported to
have disadvantages compared with methohexital: thiopental
may have a higher incidence rate of postictal cardiac
arrhythmias,1,6 whereas propofol has been shown to interfere
with seizure adequacy by raising seizure threshold and
shortening seizure duration.7
To date, no anesthetic agent has gained widespread
acceptance as a replacement for methohexital. At our
institution, both propofol and thiopental were used when
methohexital became unavailable. The authors formed a
clinical impression that thiopental had advantages over
propofol. The present study was undertaken to determine
whether this impression was accurate and to compare both
alternative agents with methohexital.
MATERIALS AND METHODS
The project was approved by the institutional research
review board of the Akron General Medical Center; however,
because of the retrospective nature of the study, informed
consent was waived. A list of all patients treated with ECT
during a 23-month period (January 2001 to December 2003)
was obtained. Electronic medical records for the 95 patients
treated during the study interval were reviewed. Information
regarding patient age, sex, date of treatment, number of days
since the previous treatment, anesthetic agent used, duration
of seizure, total energy applied, whether the patient missed a
seizure/required restimulation, and whether the patient
exhibited a postictal cardiac arrhythmia were collected. No
diagnosis or patient-identifying information was collected.
Exclusionary criteria for the cases included the use of
concurrent anticonvulsive medications, incomplete records,
use of an anesthetic agent other than those included in this
study, or the administration of ECT in the same course of
treatment at a different institution.
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Swaim et al
TABLE 1. Descriptives for Seizure, Arrhythmia, Seizure Duration, and Energy Administered
Missed Seizure Arrhythmia
Prevalence Prevalence
Methohexital 22/559 15/559
Propofol 7/79 0/79
Thiopental 13/404 8/404
All treatments were administered using a Spectrum
5000Q machine (Mecta Corporation). The initial treatment
settings were determined according to the preselected dosage
method outlined in the machine’s manual and adjusted on an
individual basis to achieve a goal of seizures of at least 25
seconds in duration. All treatments used a bilateral-stimulus
electrode placement because of the second author’s pref-
erence for this placement. Effective muscle relaxation was
obtained with succinylcholine, and either atropine or
glycopyrrolate was used as an anticholinergic agent. An
anesthesiologist was present during all treatments. Seizure
duration was determined by a 2-channel EEG recording.
The criteria for defining arrhythmia or missed seizure
were that either adverse event must be mentioned in the
progress notes or in ECT flow sheet of the patient’s chart. The
arrhythmias observed in this study were postictal tachycardia
(heart rate, 9100 beats per minute) and bradycardia (heart
rate, G60 beats per minute); although individual premature
ventricular contractions were commonly observed, their
frequency is not routinely recorded in the medical record.
No life-threatening cardiac arrhythmias were observed.
Using the Statistical Package for the Social Sciences
software, the data were analyzed to identify significant
differences on the outcome variables and their link to the
anesthetic agent. The relationships investigated were those
between the anesthetic agent and arrhythmia, seizure duration,
missed seizure, and energy administered.
RESULTS
Data were gathered for 1042 treatments; of these, 559
(53.6%) used methohexital, 79 (7.6%) used propofol, and 404
(38.7%) used thiopental. The mean age of all subjects was
55.64 years (SD, T16.57 years; range, 22Y88 years). Seventy-
nine percent of treatment records were from female patients,
20.9% were from male patients, and 0.1% did not have a
classification of sex.
Missed Seizures
Missed seizure was reported in 42 encounters (0.04%).
The remaining 1000 (95.9%) achieved seizure on first
stimulation. One record did not indicate an information
regarding the presence or the absence of seizure; this
represents 0.1% of all surveyed cases. Of those cases in
which a missed seizure was recorded, 22 of 559 treatments
with methohexital resulted in missed seizure, which repre-
sents 3.9% of the sample population treated with methohexi-
tal, or 52.4% of all cases wherein a seizure was missed
(Table 1). Of the 79 recorded cases treated with propofol,
7 missed seizures were reported, representing 11.3% of the
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J ECT & Volume 22, Number 4, December 2006
Seizure Duration (seconds), Energy Administered (Joules),
No. Patients No. Patients
51.53 (537) 75.94 (537)
42.79 (72) 81.91 (72)
47.52 (391) 69.9 (391)
propofol treatment group, or 16.7% of all cases wherein a
seizure was missed. In the final group, which was treated
with thiopental, 13 cases of missed seizure in a treatment
group total of 404 were recorded. This equates to 3.2% of
the cases of missed seizure within this anesthetic agent group
and to 31% of the cases of missed seizure. The result of a W2
test of independence revealed nonsignificance (W22 = 0.47;
P = 0.065; N = 1042).
Arrhythmia
Arrhythmia was reported in 23 cases (2.2%) in the total
sample (Table 1). Fifteen (65.2% of arrhythmia cases) of 559
encounters with methohexital, 8 (34.8% of arrhythmia cases)
of 404 encounters with thiopental, and none (0%) with
propofol resulted in arrhythmia. Despite these apparent
frequency differences, the result of a W2 test of independence
showed nonsignificance (W22 = 2.47; P = 0.291; n = 1019)
when comparing the anesthetic agents and the frequency of
arrhythmia.
Seizure Duration
Seizure duration for those who achieved seizure was
recorded (Table 1) and analyzed. Omnibus general linear
model (GLM) univariate analysis of variance (ANOVA)1
indicated that there were significant differences (F2,997 =
10.67; P G 0.01) among the 3 anesthetic groups with respect to
seizure duration. Post hoc multiple comparisons (Games-
Howell procedure) demonstrated the following pattern of
differences between the means of each group regarding
seizure duration: P e 0.001 for methohexital and propofol, P =
0.002 for methohexital and thiopental, and P = 0.070 for
thiopental and propofol. The methohexital group’s average
seizure duration (51.53 seconds) was significantly longer than
that of propofol-treated (42.79 seconds) or thiopental-treated
(47.52 seconds) patients.
Energy Administered
The mean energy administered for all groups was
74.02 J (SD, T40.73 J; range, 7.20Y174.10 J) in those who
achieved seizure (n = 1000). Differences between the amount
of energy administered and the type of anesthetic used were
noted (Table 1). Omnibus GLM univariate ANOVA was
1
Examination of the variance within each anesthetic agent group indicated a
significant difference in the variances between each of these groups.
Accordingly, GLM ANOVA in SPSS was conducted for overall
comparisons, with post hoc comparisons using the Games-Howell
procedure, which is designed for unequal variances and unequal sample
sizes and is based on the Q statistic distribution.
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J ECT & Volume 22, Number 4, December 2006
conducted to determine the presence of significant differences
in energy administered by the type of anesthetic. A significant
difference between all groups was found (F2,997 = 3.94; P =
0.020). In post hoc multiple comparisons using the Games-
Howell procedure, significant differences were found between
the amounts of energy required for the propofol and the
thiopental groups, with a mean difference of 11.97 J (SEM,
4.18), such that more energy was administered in the propofol
group (P = 0.018).
DISCUSSION
The results demonstrate that there are differences in
anesthetic agents on variables that have important treatment
implications, and a lack of differences where the literature
suggests that differences are likely to exist.
Missed Seizure
With an occurrence rate of 0.04% in our sample, missed
seizure was infrequently encountered. With a low frequency
of occurrence in the total analysis, the power to detect
differences between frequencies of missed seizure on the
basis of the anesthetic agent administered was very low. Note
that these results did approach statistical significance.
Propofol shows an elevated chance of resulting in missed
seizure (8.9%), whereas those of methohexital and thiopental
are similar and are much less (3.9% and 3.2%, respectively).
Seizures resulting from a second application of energy are
less well generalized through the brain and are more likely to
result in cognitive adverse effects.1,8 Given the pattern of
results in our data, further investigation of the effect of
propofol on the likelihood of missed seizure seems warranted.
Arrhythmia
With a low frequency of occurrence in the analysis
(2.2%), the power to detect differences between the occurrence
frequencies of arrhythmia on the basis of the anesthetic agent
administered was very low and may explain our failure to detect
a statistically significant difference. Unlike missed seizure,
cardiac arrhythmia is the leading cause of ECT-related
mortality/morbidity and requires immediate intervention.1
Consistent with known properties of the anesthetic agent, no
cases of cardiac arrhythmia were observed in study cases
treated with propofol. Although it has been reported that
postictal arrhythmia has been linked to anesthetic choice,6 we
did not observe any difference across the 3 groups. Careful
patient selection and liberal use of esmolol for tachycardia in
the immediate postictal period may contribute to the low overall
rate of arrhythmia at our institution. The results of our study
suggest that the choice of anesthetic agent may have little or no
effect on the frequency of arrhythmia after ECT treatments.
Seizure Duration
The use of the anesthetic agent methohexital is
associated with longer seizure durations, and this difference
is statistically significant in comparison with both propofol
(mean difference, 8.74 seconds) and thiopental (mean
difference, 4.01 seconds). There was no statistically sig-
nificant difference between seizure durations when directly
comparing propofol with thiopental. Provided that the EEG
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Comparison of Anesthetic Agents in ECT
seizure produced extends past the minimum 25 seconds,1 a
standard difference of 5 to 9 seconds between groups may not
be important; however, the implications of this finding need
continued study.
Energy Administered
The use of the anesthetic agent propofol is associated with
higher administered doses of energy; in comparison with
thiopental, this difference is statistically significant (mean dif-
ference, 11.98 J). The comparative differences observed between
the other anesthetic agents failed to achieve significance.
Combined Effects
The relationship between the energy delivered and the
seizure duration was investigated across the anesthetic
groups. The ideal anesthetic agent for ECT minimizes the
amount of energy required to stimulate seizure and generates
seizures of sufficient length. Figure 1 depicts the comparisons
between agents along these 2 key dimensions side by side. As
illustrated, the propofol group required the most energy and
had the shortest seizure durations. The methohexital group
required an intermediate amount of energy and provided the
longest seizure duration. The thiopental group required the
least amount of energy and had an intermediate seizure
length. Patients taking propofol require higher does of energy
to produce a seizure and have the shortest seizure durations of
all 3 groups. Decreased seizure length has been widely
studied as an indicator of decreased efficacy, with no clear
conclusions.9 Previous research shows that the larger the
amount of energy administered to a patient, the higher is the
risk of cognitive adverse effects.1 These observations suggest
that propofol may not be an adequate anesthetic agent for all
ECT encounters. Thiopental and methohexital have more
moderate results in seizure duration and energy administra-
tion, and they may be the preferable agents to increase
efficacy and reduce the amount of adverse effects.
FIGURE 1. Combined comparison of seizure duration and
administered energy.
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Swaim et al
Conclusions
Retrospective study demonstrates that the use of
propofol in ECT is associated with shorter seizure duration
and is also correlated with higher administered doses of
electric energy and decreased incidence rate of arrhythmia.
The shortened seizure duration and the higher doses of
administered energy are 2 reasons why propofol has clear
disadvantages for widespread use as an anesthetic agent for
ECT. Thiopental, however, seems to be comparable with
methohexital in seizure achievement rates and occurrence of
arrhythmia; in addition, it is able to produce medium-length
seizure durations at a low energy level.
There may be additional variables relevant to the choice
of ECT anesthetic agent that we did not study. Propofol is
known to have an advantage over barbiturate anesthetics
because of shorter recovery times, a desirable property for ECT
anesthesia. This advantage is offset by the fact that much of the
patients’ recovery time is determined by their postictal state.
There may also be differences among anesthetic agents in the
number of treatments required to achieve remission or a more
indirect measure of treatment efficacy, such as the amount of
slow-wave EEG activity or relative electric silence after seizure
endpoint. Nevertheless, inasmuch as methohexital has become
available again, we have returned to using it exclusively.
Limitations
The shortcomings of this study were due to its
retrospective nature. The dose-response information for
each of the anesthetics could not be collected and could
impact the key variables studied in this investigation.1,8 It was
not taken into consideration whether the patients had a
preexisting heart or vascular condition, which could possibly
affect the data involving cardiac arrhythmia. Other comor-
bidities and patient age (although collected, this data field was
not evaluated in relation to the treatment variables) also
remain unaccounted for; EEG seizure duration has been
shown to be inversely related to age and degree of
comorbidity.5 The sample was essentially nonrandom and
unevenly distributed among sex and ethnicity, the procedure
itself was uncontrolled, and only the cases in which the
charting was complete and accurate could be used. The
specific diagnoses of subjects in the study were also not
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J ECT & Volume 22, Number 4, December 2006
examined. Although almost all patients treated at our
institution have severe depression, this is potentially prob-
lematic because earlier studies have suggested that seizure
threshold is lower in patients with mania than in those with
depression.10,11
ACKNOWLEDGMENTS
The authors thank the Akron General Medical Center
Development Foundation and the Akron General Medical
Center Department of Medical Education for their generous
financial support, without which this research would not have
been possible.
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