The Comparative Effects of Propofol Versus Thiopental on
Middle Cerebral Artery Blood Flow Velocity During
Shigeru Saito, MD, Yuji Kadoi, MD, Takeshi Nara, MD, Makoto Sudo, MD, Hideaki Obata, MD,
Toshihiro Morita, MD, and Fumio Goto, MD
Department of Anesthesiology & Reanimatology, Gunma University School of Medicine, Maebashi, Japan
Electroconvulsive therapy provokes abrupt changes in
both systemic and cerebral hemodynamics. An anes-
might be more suitable for patients with intracranial
of our present study was to compare the effects of thio-
continuously compared cerebral blood flow velocity at
the middle cerebral artery (MCA) during electrocon-
vulsive therapy, using propofol (1 mg/kg, n ? 20) ver-
sus thiopental (2 mg/kg, n ? 20) anesthesia. Systemic
hemodynamic variables and flow velocity at the MCA
were measured until 10 min after the electrical shock.
Heart rate and arterial blood pressure increased in the
was observed to 1 min after the electrical shock. Mean
flow velocity at the MCA decreased after anesthesia in
both groups, and increased at 0.5–3 min after the elec-
after the shock in the propofol group. The flow veloci-
ties at 0.5–5 min after the electrical shock were signifi-
cantly more rapid in the thiopental group compared
with the propofol group.
(Anesth Analg 2000;91:1531–6)
10 min, the anesthetics used for ECT should have a
short action and a rapid recovery profile. In addition,
because the seizure itself is believed to be important
for the efficacy of the therapy, the anesthetics should
not interfere with the electrical seizure. Until now,
short-acting barbiturates, such as methohexital and
thiopental, were the commonly used anesthesia (1).
More recently, propofol at ?1 mg/kg has also been
recommended for ECT anesthesia (2,3). Many studies
demonstrated that hemodynamics during ECT using
propofol anesthesia were more stable than those using
barbiturate anesthesia (2–5).
ECT induces an abrupt change in cerebral hemody-
namics and systemic circulation (1,6). In a previous
study, we reported that cerebral blood flow velocity at
the middle cerebral artery (MCA) is drastically
changed by the application of electrical shock (7). This
lectroconvulsive therapy (ECT) is effective for
drug-therapy resistant severe depression. Be-
cause the therapy can be completed within
finding was confirmed by Vollmer-Haase et al. (8).
Two mechanisms have been proposed for the hyper-
emia during ECT (6,9): 1) cerebrovascular regulation,
which meets the increased cerebral oxygen demand
during seizure with the oxygen supply from the cere-
bral blood stream, and 2) a secondary effect of the
systemic hyperdynamic state, which is induced by the
excessive release of catecholamines. Although the ef-
fects of propofol on seizure and systemic circulation
are not identical with those of thiopental, how propo-
fol differs from thiopental regarding changes in cere-
bral hemodynamics during ECT is unknown. In our
present study, we continuously compared cerebral
blood flow velocity at the MCA during ECT by using
propofol versus thiopental anesthesia. The dose of
thiopental we used was 2 mg/kg, as in our previous
study. The dose of propofol was 1 mg/kg, which was
the minimal dose to induce unconsciousness.
Informed consent was obtained from the patient or,
when necessary, the appropriate relative. Our study
protocol was approved by a local Clinical Study Com-
mittee. ECT was prescribed for 40 patients with en-
dogenous depression. The patients ranged from 16 to
Accepted for publication August 11, 2000.
Address correspondence and reprint requests to Shigeru Saito,
MD, Department of Anesthesiology & Reanimatology, Gunma Uni-
versity School of Medicine, 3-39-22, Showamachi, Maebashi, 371-
8511, Japan. Address e-mail to firstname.lastname@example.org.
©2000 by the International Anesthesia Research Society
0003-2999/00 Anesth Analg 2000;91:1531–6
69 yr of age, and were in good physical heath. No
patient had cardiovascular or cerebrovascular compli-
cations, or drug allergy. All patients were treated
more than six times (three times per week at 2-day
intervals). The data were obtained in the second ECT
trial in each case. The selection of thiopental or propo-
fol was determined by a random table. All persons
present at the ECT session were blinded to the identity
of the study drugs (drugs were given from a foil-
covered cylinder and lines). The data obtained were
analyzed later by an individual who was also blinded
to the treatment regimens.
To avoid an unfavorable parasympathetic reflex,
atropine (0.01 mg/kg IM) was given as premedication.
Arterial blood pressure (BP) was measured continu-
ously at the right radial artery by using a tonometric
BP monitor (CBM-7000™; Colin Co. Ltd., Komaki,
Japan). The tc-Doppler (TC2–64™; EME Co. Ltd.,
Uberlingen, Germany) probe was adjusted to detect
MCA flow from the right temporal side. General an-
esthesia was induced with thiopental (2 mg/kg) or
propofol (1 mg/kg). One of these drugs was admin-
istered over 15 s through an indwelling IV catheter.
After loss of consciousness, succinylcholine chloride
(1 mg/kg) was administered and ventilation was as-
sisted using a face mask and 100% oxygen. One
minute after the injection, an electrical current was
applied bilaterally for 5 s at the minimal stimulus
intensity, which had been determined in the first ECT
trial by a stepwise increase in electrical intensity. The
electroshock stimulus was delivered by a trained psy-
chologist using an ECT-stimulator (CS-1™; Sakai Iryo
Co. Ltd., Tokyo, Japan). The efficacy of electrical stim-
ulation was determined by the “tourniquet tech-
nique”—that is, by observation of convulsive move-
ments of the distal leg, around which an inflated
tourniquet was set to block the distribution of muscle
relaxant. The end-expiratory CO2partial pressure
(end-tidal CO2) at nostrils and arterial blood oxygen
saturation (Spo2) were monitored by a respiration
monitor (Capnomac Ultima™; Datex Co. Ltd., Hel-
sinki, Finland), and end-tidal CO2tension was main-
tained at 30–35 mm Hg and the Spo2value (measured
at left index) above 98% by manual ventilation assis-
tance throughout the therapy.
The flow velocity at the MCA was measured by
using a 2-MHz ultrasonic wave. The Doppler signals
were obtained through the right temporal window at
a depth of 45–55 mm from the surface. The signal
quality was determined from the characteristic high
pitch sound and from the waveform of the displayed
sonogram. The velocity was calculated automatically
by tracing the waveforms every 5 s.
The data were expressed as mean ? sd. Data were
compared by analysis of variance for repeated meas-
ures with a P value ? 0.05 considered statistically
significant. For comparison of each mean value, two-
way analysis of variance was applied and post hoc
testing was performed by using the Scheffe ´ method
(StatView 5.0™; SAS Institute, Cary, NC).
There was no significant difference between the de-
mographics of the patients in the two groups (Table 1).
Patients had been prescribed multiple psychiatric
medications at various doses in their history (Table 2).
However, they were unresponsive to drug therapy,
and the medications were interrupted at least 1 day
before the start of ECT sessions. Heart rate in the
thiopental group significantly increased after the ap-
plication of electrical shock, and the increase contin-
ued until 5 min after the electrical shock (Figure 1).
Maximal heart rate was observed 1 min after the elec-
trical shock, and was 31% ? 13% more rapid than the
preanesthesia control value. In the propofol group,
heart rate did not change significantly throughout the
ECT trial. Mean BP in the thiopental group increased
by 39% ? 9% at 30 s after the electrical shock (Fig-
ure 2). The increase continued until 5 min after the
electrical shock. In the propofol group, an increase in
mean BP was observed at 1 min after the electrical
shock (17% ? 13% more than the preanesthesia value).
Mean BP at preanesthesia control measurement and
immediately before the electrical shock did not differ
significantly between the thiopental and propofol
groups. However, the values after the electrical shock
(0.5, 1, 2, 3, and 5 min) were significantly increased in
the thiopental group compared with the propofol
Mean flow velocity at the MCA decreased after
anesthesia in both groups (preanesthesia 56 ? 18 cm/s
to 43 ? 9 cm/s in the thiopental group, preanesthesia
58 ? 18 cm/s to 45 ? 4 cm/s in the propofol group)
(Figure 3). The values at preanesthesia control mea-
surement and immediately before the electrical shock
did not differ significantly between groups. The flow
velocity increased at 0.5–3 min after the electrical
shock in the thiopental group. In the propofol group,
an increase in the flow velocity was observed at 0.5
and 1 min after the electrical shock. The flow velocity
trend in the thiopental group and that in the propofol
group was significantly different (P ? 0.01), and the
values at 0.5, 1, 2, 3, and 5 min after the electrical shock
were significantly increased in the thiopental group
compared with the propofol group. Mean seizure du-
ration was 38 ? 18 s in the thiopental group and 27 ?
18 s in the propofol group. The duration in the propo-
fol group was significantly shorter than that in the
thiopental group (P ? 0.05).
SAITO ET AL.
MIDDLE CEREBRAL ARTERY FLOW DURING ECT
Ideal anesthetics used for ECT should have characteris-
tics that include rapid induction, short duration of ac-
tion, minimal side effects, rapid recovery, and no inter-
ference with the ECT efficacy. Because of its rapid
induction and rapid recovery, propofol was recently in-
pared the use of propofol for ECT with barbiturates,
which have long been used for ECT anesthesia (2–5,10).
These studies demonstrated that propofol anesthesia re-
duced seizure duration compared with barbiturates. The
approximately 20% shorter seizure duration observed in
our propofol group was comparable to a previous report
by Boey and Lai (4). Although seizure duration has been
considered crucial for ECT therapeutic efficacy, two psy-
chiatric reports conclude that the efficacy of ECT using
propofol did not differ significantly from that using bar-
biturates (5,11). In those reports, which could not dem-
onstrate any difference in outcome, several different
types of psychiatric rating methods, such as the
Hamilton Scale, Beck Inventory, and Montgomery-
Asberg Rating (11,12), were used. Because the dose
of propofol and the duration of seizure have an
inverse relationship, we tried doses ?1 mg/kg to
obtain a longer seizure in our preliminary study.
However, propofol ?1 mg/kg was not enough for
many patients to lose consciousness. Fredman et al.
(2) reported that patients lost consciousness after a
bolus infusion of 0.75 mg/kg of propofol. This dis-
crepancy may be explained by the difference in the
premedication protocol and by the racial differences
of the subjects.
after electrical shock in the thiopental group. This phe-
nomenon and the degree of alterations were comparable
with our previous observation (7). In contrast, these sys-
temic circulatory changes were mostly abolished in the
ing ECT using propofol were described previously (2–5).
Boey and Lai (4), who compared ECT using thiopental
and propofol as in the present study, demonstrated no
alteration in either heart rate or BP after electrical shock
using propofol. Several other studies have compared
Figure 1. Heart rate during electroconvulsive therapy. Heart rate
in the thiopental group significantly increased after the application
of electrical shock, and the increase continued until 5 min after the
electrical shock (*P ? 0.01). In the propofol group, heart rate did not
change significantly throughout the electroconvulsive therapy trial.
The heart rate trend in the thiopental group and that in the propofol
group were significantly different (P ? 0.01), and the values imme-
diately after anesthesia and at 0.5, 1, 2, 3, and 5 min after the
electrical shock were significantly higher in the thiopental group
compared with the propofol group (†P ? 0.01).
Table 1. Demographic Data of Patients
56 ? 16
51 ? 10
161 ? 11
163 ? 12
53 ? 9
51 ? 7
100 ? 4
103 ? 7
Values are mean ? sd.
Table 2. Psychiatric Medications Before Electroconvulsive
SAITO ET AL.
MIDDLE CEREBRAL ARTERY FLOW DURING ECT
methohexital and propofol, and demonstrated minor he-
modynamic changes during ECT using propofol
compared with methohexital (2–5). Fredman et al.
(2) reported that 0.75 mg/kg propofol, which is
smaller than the doses used in other studies, could
ensure stable hemodynamics by using labetalol be-
fore the electrical shock.
Flow velocity at the MCA doubled after electrical
shock in the thiopental group. This observation was
comparable with our previous report (7), and the phe-
nomenon was confirmed by Vollmer-Haase et al. (8).
The flow velocity increase was also observed in the
propofol group; however, the degree of increase was
modest and the duration was shorter compared with
those in the thiopental group. Flow velocity at the
MCA is considered an indicator of cerebral blood flow
(13,14). This idea is based on the premise that the
diameter of an insonicated vessel remains constant.
Previous studies have demonstrated that the diameter
of the MCA is not significantly affected by changes in
carbon dioxide tension (15), BP (16), or the adminis-
tration of anesthetic or vasoactive drugs (17). How-
ever, Jansen et al. (18) recently reported that in a
pathologic condition such as brain tumor, the correla-
tion between cerebral blood flow and cerebral blood
flow velocity at the MCA should be interpreted with
caution. Although it is possible that an electrical cur-
rent of ECT directly induces vessel diameter changes,
as observed during in vitro experiments (19), this re-
sponse is tentative. Most alterations in systemic and
cerebral hemodynamics after the electrical shock have
been thought to be derived from humoral and neuro-
nal factors (1), and these factors may not induce vessel
diameter change at the MCA. Therefore, it is possible
that the changes in cerebral blood flow velocity in the
present study reflect changes in cerebral blood flow.
Propofol induces cerebral vasoconstriction, and re-
duces cerebral blood flow and intracranial pressure
(20). Cerebral metabolic rate is also reduced by the
administration of propofol (21). In the present study,
Figure 2. Mean blood pressure during electroconvulsive therapy.
Mean blood pressure in the thiopental group increased at 30 s after
the electrical shock. The increase continued until 5 min after the
electrical shock (*P ? 0.01). In the propofol group, an increase in
mean blood pressure was only observed at 1 min after the electrical
shock (#P ? 0.01). The trend of mean blood pressure in the thio-
pental group and that in the propofol group was significantly
different (P ? 0.01). Mean blood pressure at preanesthesia control
measurement and immediately before the electrical shock did not
differ significantly between the thiopental and propofol groups.
However, the values after the electrical shock (0.5, 1, 2, 3, and 5 min)
were significantly increased in the thiopental group compared with
the propofol group (†P ? 0.01).
Figure 3. Mean flow velocity at the middle cerebral artery (MCA)
during electroconvulsive therapy. Mean flow velocity at the MCA
decreased after anesthesia both in the thiopental and the propofol
groups (¶P ? 0.05). The flow velocity increased at 0.5–3 min after
the electrical shock in the thiopental group (*P ? 0.01). In the
propofol group, an increase in the flow velocity was observed at 0.5
and 1 min after the electrical shock (#P ? 0.01). The flow velocity
trend in the thiopental group and in the propofol group were
significantly different (P ? 0.01), and the values at 0.5, 1, 2, 3, and
5 min after the electrical shock were significantly increased in the
thiopental group compared with the propofol group (†P ? 0.01).
SAITO ET AL.
MIDDLE CEREBRAL ARTERY FLOW DURING ECT
flow velocity at the MCA decreased immediately after
anesthesia induction both in the thiopental and propofol
groups (23% ? 18% in the thiopental group and 22% ?
18% in the propofol group, respectively). This finding
suggests that 1 mg/kg propofol and 2 mg/kg thiopental
decreases cerebral blood flow to the same extent, and
supports the notion that the effects of propofol on cere-
bral blood flow appear to be similar to those of barbitu-
rates (20). This observation is consistent with the report
by Thiel et al. (22), who compared the effects of induc-
tion doses of propofol and thiopental on cerebral blood
flow velocity. Also, according to the pharmaceutical in-
formation, rate constants of the distribution phase of
propofol and thiopental are very similar (23).
Two hypotheses have been proposed to explain hy-
peremia after electrical shock (6,9). One states that
cerebral blood flow is augmented to meet the in-
creased cerebral tissue oxygen and energy demand
during seizure. The second states that cerebral hemo-
dynamics may be influenced by drastic changes in
systemic hemodynamics after the electrical shock. We
have reported that the regional oxygen saturation
change detected by a near-infrared cerebral oxymeter
correlated with the changes in systemic hemodynam-
ics after electrical shock (24). In the present study,
seizure duration was shorter in the propofol group.
The potent anticonvulsive property of propofol might
be a potential mechanism for the minor reaction to
electrical stimulus (23). This shorter seizure, and the
probable smaller energy demand change, may have
been a cause of the minor increase in cerebral blood
flow velocity in the propofol group. Also, in the
propofol group, the systemic hemodynamic change
was small. This smaller change in systemic hemody-
namics may have been another cause of the minor
change in cerebral hemodynamics. In the present
study, we examined the effect of propofol and thio-
pental at singular doses, simply because the doses we
used were often used in clinical settings. To compare
the pharmacologic actions of propofol and thiopental
on cerebral hemodynamics extensively, further exam-
ination at the other doses is required.
intracerebral aneurysm and was safely treated by ECT
using methohexital anesthesia. In several previous case
reports including this one, antihypertensive medi-
cations such as ?-blocker and sodium nitroprusside,
were used to attenuate the expected intracranial hemo-
dynamic change. Considering systemic and cerebral he-
modynamic stability during ECT, propofol anesthesia
might be more suitable than barbiturates as anesthesia
for patients who have intracranial complications.
The authors thank Dr. Takushirou Akada (Department of Psychia-
try, Gunma University) for his cooperation with this study, and
Forte Inc. (Tokyo) for English editing.
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