Keywords
electroconvulsive therapy - patient state index - propofol - anesthesia depth - maximum
sustained coherence
Introduction
Electroconvulsive therapy (ECT) is the most effective treatment for resistant and
more severe affective and psychotic disorders [1]. Its therapeutic effect is achieved by inducing various grand mal
seizures of adequate quality. On the other hand, seizures that lack that quality can
lead to therapeutic failure [2]. Modified
ECT involves the use of anesthetic agents such as propofol, which can increase the
seizure threshold and, thus, make optimal seizure difficult [3]. Excessively deep anesthesia can reduce
the antidepressant effect of ECT and increase cognitive side effects due to the need
for higher stimulus energy [3].
Various strategies for improving seizure quality include: hyperventilation,
modification of the stimulus parameters, changing the position of the electrodes,
use of anesthetic agents with less anticonvulsant activity, the addition of opiates
such as remifentanil, use of oral theophylline or intravenous caffeine or flumazenil
before applying the stimuli, delaying the moment of stimulation with respect to the
anesthetic induction, or use of monitors of the depth of anesthesia [4]
[5]
[6]. Among the monitors, the
bispectral index has been the most studied. It has been shown to be useful in
determining a state of less profound narcosis when inducing seizures [6]
[7]
[8]. Other authors who used
the NarcotrendTM monitor also found an association between higher values
of the anesthetic depth index and higher seizure quality [9]. The SedLineTM monitor
calculates the patient state index (PSI) based on the spectral analysis of four
simultaneous channels of the electroencephalogram (EEG) with an algorithm that
incorporates a high heterogeneity of the variance at different levels of
sedation/hypnosis and takes into account the brain anterior-posterior axis, as well
as the coherence between bilateral regions. It provides values on a scale from 0 to
100, with the latter corresponding to the waking state [10]
[11].
The use of the PSI in ECT may provide advantages over the bispectral index, because
while it has been shown to equally predict loss of consciousness, it is superior in
detecting intraoperative awakening [12]
and is less sensitive to sources of electrical interference [11]
[13]. The proposed hypothesis was that patients monitored with the PSI
would experience seizures of higher quality (in terms of duration,
electroencephalographic expression, and automated parameters) compared to the group
treated with the traditional clinical method.
Materials and Methods
This prospective experimental study was conducted with two groups. One group received
ECT determining the moment of stimulation by measuring the anesthetic depth with the
PSI (i. e., the PSI group); the other was a control group (application of ECT), in
which the procedure was based on the clinical assessment of the patients.
Sample
The present study sample consisted of 51 patients who underwent a total of 346
sessions: 134 for the PSI group, and 212 for the control group. The patients
were admitted to the Psychiatric Unit Benito Menni CASM-HGG and recruited
between November 2017 and March 2023. The inclusion criteria were the diagnosis
of major depressive disorders according to the Diagnostic and Statistical Manual
of Mental Disorders (DSM-IV-TR) [14]
and the indication of ECT (i. e., intense inhibition, high suicidal risk,
psychotic symptoms, intense anxiety or agitation, history of response to ECT,
lack of response or intolerance to psychopharmacological treatment) [15]. The exclusion criteria were: the
presence of epilepsy, a history of electroencephalographic alterations due to
other pathologies or current treatment with anticonvulsants, active use in the
context of substance abuse or dependence according to DSM-IV-TR in the previous
6 months, American Society of Anesthesiologists (ASA) criteria>3, performance
of ECT in the previous 6 months, or outpatient ECT.
Demographic and clinical characteristics are shown in [Table 1]. Four patients ended the
study prematurely—three due to voluntary withdrawal and one due to a Coronavirus
disease-2019 infection, although their sessions were included in the study. Of
the initial sample of 360 sessions, 14 were excluded from the PSI group as their
values fell outside the range considered for stimulation.
Table 1 Sociodemographic and ECT procedure
characteristics.
|
PSI
|
Control
|
Statistical analysis
|
|
|
|
|
test
|
p
|
|
Patients (n)
|
25
|
26
|
|
|
|
Sex n (%)
|
|
|
|
|
|
Male
|
8 (32)
|
12 (46.2)
|
ꭓ2=1.07; df=1
|
0.30
|
|
Female
|
17 (68)
|
14 (53.8)
|
|
|
|
Age mean (SD)
|
62.16 (13.33)
|
64.59 (12.93)
|
Mann-Whitney U test=279.5
|
0.39
|
|
BMI mean (SD)
|
24.70 (4.37)
|
24.77 (5.40)
|
Mann-Whitney U test=315
|
0.85
|
|
Current episode in days mean (SD)
|
123.24 (104.03)
|
136.85 (146.39)
|
Mann-Whitney U test=314
|
0.83
|
|
Years of illness mean (SD)
|
18.63 (14.36)
|
19 (17.60)
|
Mann-Whitney U test=305
|
0.71
|
|
Previous episodes mean (SD)
|
2.08 (2.18)
|
1.69 (2.07)
|
Mann-Whitney U test=267
|
0.37
|
|
HDRS-17 score at baseline mean (SD)
|
20.4 (6.58)
|
22,6 (5.75)
|
Mann-Whitney U test=238.5
|
0.15
|
|
CGI (Clinical Global Impression) at baseline
|
|
|
|
|
|
4
|
14 (56)
|
11 (42.3)
|
Fisher’s exact=2.29
|
0.54
|
|
5
|
6 (24)
|
9 (34.6)
|
|
|
|
6
|
4 (16)
|
6 (23.1)
|
|
|
|
7
|
1 (4)
|
0 (0)
|
|
|
|
ASA
|
|
|
|
|
|
I
|
1 (4)
|
1 (3.8)
|
Fisher’s exact=5.17
|
0.10
|
|
II
|
19 (76)
|
21 (80.8)
|
|
|
|
III
|
5 (20)
|
4 (15.4)
|
|
|
|
Sessions n
|
134
|
212
|
|
|
|
Dose of lorazepam mg, mean (SD)
|
1.80 (1.25)
|
2.62 (1.42)
|
Mann-Whitney U test=8145.5
|
0.007
|
|
Atropine use n (%)
|
|
|
|
|
|
yes
|
6 (4.5)
|
26 (12.3)
|
ꭓ2=5,93; df=1
|
0.015
|
|
no
|
128 (95.5)
|
186 (87.7)
|
|
|
|
Dose of atropine mg/kg, mean (SD)
|
0.0081 (0.0025)
|
0.0074 (0.0023)
|
Mann-Whitney U test=62
|
0.44
|
|
Sat O2 (%) pre-stimulus mean (SD)
|
98,77 (1.34)
|
99.13 (0.92)
|
Mann-Whitney U test=8023.5
|
0.014
|
|
Dose of propofol mg/kg, mean (SD)
|
1.13 (0.32)
|
1.07 (0.30)
|
Mann-Whitney U test=8756
|
0.074
|
|
Dose of succinylcholine mg/kg, mean (SD)
|
0.68 (0.23)
|
0.64 (0.13)
|
Mann-Whitney U test=9544.5
|
0.52
|
|
Electrode placement n (%)
|
|
|
|
|
|
BL
|
100 (74.6)
|
193 (91)
|
ꭓ2=17.05; df=1
|
0.000
|
|
RUL
|
34 (25.4)
|
19 (9)
|
|
|
|
Stimulus energy mC, mean (SD)
|
218.47 (115.6)
|
254.22 (110.33)
|
Mann-Whitney U test=10672.5
|
0.000
|
ECT: electroconvulsive therapy; BMI: body mass index; Sat O2:
oxygen saturation on pulse oximeter; SD: standard deviation.
Study Variables
The variables assessed were those related to patients (age, sex, body mass index
[BMI]); anesthetic risk level (ASA); episode and disorder (time, severity, and
symptomatology, pharmacotherapy); session procedure (session number, oximetry,
and heart rate, dose of propofol, atropine, and muscle relaxant); application of
the stimuli (electrode placement and energy level used) ([Table 1]).
[Table 2] illustrates the variables
that measure seizure quality, such as motor and EEG seizure times, and the
quality and extent of the seizures, including heart rate variations. Seizures
were considered adequate if the following criteria were met: (a) motor seizure
time≥20 s or≥25 s in the EEG, (b) average seizure energy index>3,500
microV2; (c) postictal suppression index>70%, and (d) maximum
sustained coherence (MSC)>90% (motor seizure Time, ASEI, postictal
suppression Index and MSC (TAIM) criteria).
Table 2
Variables to assess seizure quality.
|
Motor seizure time
|
Adequate if ≥ 20 s
|
|
Electroencephalogram (EEG) seizure time
|
Adequate if ≥ 25 s
|
|
Characteristic phases in EEG
|
One point for each phase present (hypersynchronous polyspikes, polyspikes-slow waves,
and postictal suppression), with a maximum of 3 points if all were present or the
termination was clear and abrupt with subsequent flattening
|
|
EEPRS (ECT-EEG parameter rating scale)
|
Adequate if: bilateral high amplitude spike and wave phase (visual assessment, ASEI > 1000,
MIA [ASEI/tEEG] > 26) > 13 s + abrupt endpoint of seizure + adequate postictal suppression
( > 74 %) + bilateral seizure duration > 24 s
|
|
ASEI
|
Average seizure energy index
|
|
Postictal suppression index
|
Postictal suppression index
|
|
MSC
|
Maximum sustained coherence
|
|
MSP
|
Maximum sustained power
|
|
TtoPP
|
Time to peak power
|
|
TtoPC
|
Time to peak coherence
|
|
Seizure concordance
|
Motor seizure time/electroencephalographic seizure time
|
|
Central inhibition
|
Appropriate if seizure concordance was ≥ 0.8 or the postictal suppression index was ≥ 80 %
|
|
Maximal HR
|
Maximum heart rate during seizure
|
|
HR > 140 beats/min
|
Heart rate greater than 140 beats/min during the seizure
|
|
Maximal - pre-stimulus HR
|
The difference between the maximal heart rate during the seizure and that before the
electrical stimulus
|
|
motor seizure Time,
ASEI, postictal
suppression Index and
MSC (TAIM) criteria
|
Adequate seizure if it meets: (a) motor seizure time ≥ 20 s or in EEG ≥ 25 s; (b)
ASEI > 3500 microV
2
; (c) Postictal suppression index > 70 %; and (d) MSC > 90 %
|
A method similar to that of Rattehalli [16] was used to assess the characteristic phases of the EEG. In the
case of the ECT-EEG Parameter Rating Scale (EEPRS) [17], doubtful seizures were also
considered inappropriate. Seizure concordance was included as a measure of
central inhibition because it is less influenced by EEG artifacts than the
postictal suppression index [18]. When
seizure duration could not be obtained from EEG to assess the seizure duration,
motor seizure time was used instead. Unregistered automated parameters were
counted as missing values. As there is no single parameter to predict seizure
quality, following Gasteiger [9] and
Weiss [19], seizures were also
classified as adequate if they met the TAIM criteria.
It was estimated that the dose of propofol in the restimulations was equivalent
to half of that administered initially. The independent variables considered
were the position of the electrodes, sex, age, BMI, dose of lorazepam,
pre-stimulus oxygen saturation, dose of propofol, and stimulation energy. The
dependent variables were those described for the assessment of seizure
quality.
For the assessment of autonomic activation, only cases not treated with
β-blockers were considered, including the following independent variables:
position of the electrodes, sex, age, use of atropine, dose of propofol, and
stimulation energy. Measures of mood (HDRS-17) [20], severity (CGI) [21], and cognitive status with the
mini-cognitive examination (MEC) [22]
were taken in alternating sessions. Clinical response was considered when the
HDRS-17 scale score reached 75% of the initial score. Clinical remission was
defined as a score≤7 on the HDRS-17 scale and/or a score<4 on the CGI
severity score.
Procedure
The present study followed the criteria of the Declaration of Helsinki and was
approved by the Clinical Research Ethics Committee of the General Hospital of
Granollers, Spain (CEIC201073003). The patients or their relatives gave informed
consent for both ECT treatment and participation in the study. Subsequently, the
patients were randomly assigned to one of the two groups. They remained admitted
to the hospitalization unit throughout the treatment. The antidepressant dosage
remained unchanged throughout the course of the ECT. Lorazepam was used as a
hypnotic or anxiolytic but was never administered immediately before ECT
sessions. Antipsychotic or euthymizing drugs were withdrawn. Propofol was used
as an anesthetic, succinylcholine as a muscle relaxant, and atropine to prevent
asystole or treat bradycardia after the electrical stimulus. The
anesthesiologist determined the dosage of each based on weight, aiming to repeat
the same dosage in each session.
Stimulation was performed using the Thymatron SYSTEM IVTM device
(Somatics LLC, Illinois, USA). The recording of constants was performed using an
OmicromTM Vision multiparameter monitor (RGB Medical Devices SA,
Madrid, Spain), and the PSI was determined using the SedLineTM
monitor (Masimo Corporation, California, USA). Electroencephalographic recording
was performed by placing one electrode in a frontal position and two others in
each mastoid region.
Oxygenation with flow≥4 L/min was applied prior to anesthetic induction and until
recovery of spontaneous breathing after the seizures. Blood pressure, heart
rate, electrocardiographic recording, and pulse oximetry were monitored during
treatment.
The stimulus dose was calculated according to the age-based method, using a
0.5 ms pulse width for bifrontotemporal (BL) ECT or 0.25 ms for right unilateral
(RUL) ECT. The ECT application procedure was identical for both groups, except
for the decision on the moment of application of the electrical stimulus.
In the PSI group, propofol was administered first, followed by succinylcholine,
when the PSI index began to decrease. Electrical stimulation was applied when
this index showed an upward trend between values of 50 and 70. In the case of
re-stimulation, the same evolution of the PSI was awaited.
In the control group, after the administration of propofol, the cessation of the
palpebral reflex was awaited before administering succinylcholine. Electrical
stimulation was applied when succinylcholine-induced fasciculations had ended,
and the score was 6 on the Ramsay scale [23]. In cases of re-stimulation, the stimulus was not applied until
1 minute had passed since the previous seizure.
The PSI monitoring was not used in the control group and the Ramsay scale score
was not applied to the PSI group.
In both groups, restimulation was performed when the duration of the seizures was
less than 25 s in the EEG or 20 s at the motor level, increasing the energy by
50.4 mC (10%) in the second stimulus, and by 504 mC (100%) in the third,
following the same guidelines. In cases of an MEC score<23, the electrode
position became RUL. It was changed from RUL to BL ECT if no improvement had
been experienced after six sessions of starting treatment with the former. The
frequency was two sessions per week. The patients ended the study when: they
achieved clinical remission, if a stimulus of 504 mC of energy did not achieve
adequate seizures, or if there was no clinical remission after 12 sessions.
Statistical Analysis
Descriptive statistics (i. e., mean, standard deviation, and frequency) were used
to characterize the sample. A p-value<0.05 was considered
statistically significant. Graphical assessment and the Kolmogorov-Smirnov test
were used to examine the distribution of the variables. The Mann-Whitney
U-test was used to analyze quantitative variables, and the
χ2 test was used for the qualitative data. When the contribution
of the PSI in the improvement of seizure quality was assessed, linear
mixed-effects models were used for continuous variables and generalized linear
mixed-effects models for dichotomous variables. The two models allowed for the
analysis of fixed and random effects.
Due to the existence of collinearity between the variables age and energy, the
analysis was performed separately for each of them, together with the rest of
the independent variables. The statistical analysis was performed using SPSS
(Version 23; IBM Corp., New York, USA) and R software [24]. The models were adjusted for all
possible combinations of the covariates to discard those that were irrelevant.
This way, the variable lorazepam dose was discarded. Following Rothman [25], it has not been deemed necessary
to make corrections for multiple comparisons.
Results
[Table 1] presents the characteristics of
the ECT procedure. The control group received a higher dose of lorazepam during
treatment, used a greater but non-significant amount of atropine, and also exhibited
a better oxygen saturation prior to the stimuli. The PSI group was treated with
significantly more sessions using the RUL position and with a lower mean stimulus
energy. The mean PSI value before the application of the stimuli was 56.57±6.51.
[Table 3] illustrates the parameters of
seizure quality for each study group. The PSI group obtained: a higher percentage
of
adequate seizures according to the scores of the three assessment methods (EEG
phases, EEPRS, and TAIM criteria), longer seizure duration, both motor and
electroencephalographic, and higher mean values in the automated parameters. This
group also obtained better results in seizure concordance and central
inhibition.
Table 3 Parameters of seizure quality.
|
PSI
|
Control
|
|
Seizure quality (according to EEG phases) n (%)
|
|
0
|
0
|
2 (1)
|
|
1
|
7 (4.7)
|
33 (15.7)
|
|
2
|
32 (23.9)
|
85 (40.5)
|
|
3
|
95 (70.9)
|
90 (42.9)
|
|
Seizure quality (EEPRS), n (%)
|
|
Inadequate
|
1 (0.7)
|
24 (11.4)
|
|
Equivocal
|
89 (66.4)
|
141 (66.8)
|
|
Adequate
|
44 (32.9)
|
46 (21.8)
|
|
Seizure quality (meet TAIM criteria)
|
|
Yes
|
43 (34.1)
|
39 (20.9)
|
|
No
|
83 (65.9)
|
148 (79.1)
|
|
Seizure concordance, mean (SD)
|
0.68 (0.18)
|
0.58 (0.20)
|
|
Central inhibition n (%)
|
|
Adequate
|
67 (50)
|
71 (33.5)
|
|
Inadequate
|
67 (50)
|
141 (66.5)
|
|
Motor seizure time (s), mean (SD)
|
27.08 (10.23)
|
19.76 (10.72)
|
|
EEG seizure time (s), mean (SD)
|
41.13 (14.97)
|
35.28 (20.33)
|
|
ASEI (microV2) mean (SD)
|
9296.2 (9241.48)
|
7617.44 (10749.16)
|
|
ASEI>3500 microV2, n (%)
|
84 (65.6)
|
62.33 (26.69)
|
|
Postictal suppression index (%), mean (SD)
|
68.3 (27.42)
|
62.33 (26.69)
|
|
Postictal suppression index>70% n, (%)
|
59 (50.4)
|
80 (50.6)
|
|
MSP (microV2), mean (SD)
|
17848.03 (16679.65)
|
13763.72 (17079.06)
|
|
MSP>6000 microV2, n (%)
|
92 (70.2)
|
100 (55.2)
|
|
MSC (%), mean (SD)
|
90.57 (13.95)
|
82.63 (21.43)
|
|
MSC>90%, n (%)
|
98 (75.4)
|
97 (52.7)
|
|
TtoPP (s), mean (SD)
|
19.01 (16.72)
|
14.13 (8.26)
|
|
TtoPP<20 s, n (%)
|
84 (64.1)
|
149 (81)
|
|
TtoPC (s), mean (SD)
|
32.26 (64.58)
|
17.44 (10.74)
|
|
TtoPC<20 s, n (%)
|
61 (47.3)
|
126 (68.5)
|
|
Maximal HR (beats/min), mean (SD)
|
126.53 (21.86)
|
120.29 (25.06)
|
|
Maximal - pre-stimulus HR (beats/min), mean (SD)
|
37.66 (22.68)
|
29.3 (24.7)
|
|
HR>140 beats/min n (%)
|
37 (30.3)
|
37 (21.4)
|
ASEI: Average seizure energy index; EEG: electroencephalogram; EEPRS: ECT–EEG
Parameter Rating Scale; HR: heart rate; TtoPC: time to peak coherence;
TtoPP: time to peak power; MSP: maximum sustained power; MSC: maximum
sustained coherence; SD: standard deviation.
There were no significant differences between the two groups regarding clinical
improvement (clinical response: χ²=0.18, df=1, p=0.67; clinical remission:
χ²=0.64, df=1, p=0.42), nor on MEC scores at the end of the treatment
(t=-2.07, df=150.94, p=0.26).
In the linear models that included age or energy as an independent variable for
seizure quality, the use of the PSI was associated with better seizure quality
according to the EEG phases. Age, stimulus energy, propofol dosage, electrode
placement, and BMI were also associated with measures of seizure quality. Thus, in
the age model, the RUL electrode position and older age were significantly
associated with a worse score on the EEPRS and per the TAIM criteria. Conversely,
in
the energy model, the RUL electrode position was significantly related to poorer
seizure quality according to the EEG results and the EEPRS. BMI showed a
significantly negative association with seizure quality in EEG in both models ([Table 1], supplementary data).
In the two models, the PSI was positively related to better seizure concordance, both
motor seizure time and electroencephalographic time, MSC, and time to peak coherence
(TtoPC) ([Table 4]). In both models, the
propofol dosage was also significantly and inversely related to motor seizure time
and EEG seizure duration, while BMI only negatively correlated with seizure duration
in the EEG. In the model with energy as the independent variable, energy showed a
significant and inverse association with seizure concordance and with the automated
parameters maximum sustained power (MSP) and Time to peak power (TtoPP) ([Table 2], Supplementary data).
Table 4 Results of the PSI and dependent variables to
determine seizure quality according to linear models that include age or
stimulus energy models.
|
Model 1 (age)
|
Model 2 (energy)
|
|
Odds Ratio (CI)
|
|
Seizure quality (EEG)
|
6.91 (1.59, 35.28)**
|
8.11 (0,01, 0,8)**
|
|
Seizure quality (EEPRS)
|
2.2 (0.72, 6.92)
|
2.31 (0.01, 0.78)
|
|
Seizure quality (TAIM criteria)
|
2.84 (0.98, 8.91)
|
2.46 (0.01, 1.56)
|
|
HR>140 beats/min
|
1.1 (0.22, 5.53)
|
1.08 (0.21, 5.58)
|
|
Coefficient β (CI)
|
|
Maximal HR
|
3.09 (−7.05, 13.22)
|
3.69 (−6.84, 14.23)
|
|
Maximal - pre-stimulus HR
|
7.35 (−1.48, 16.23)
|
7.8 (−1.29, 16.89)
|
|
Seizure concordance
|
0.1 (0.04, 0.16) **
|
0.09 (0.02, 0.15) *
|
|
Central inhibition
|
0.14 (−0.01, 0.29)
|
0.13 (−0.02–0.28)
|
|
Motor seizure time
|
8.3 (3.38, 13.22)**
|
8.28 (3.4, 13.16)**
|
|
EEG seizure time
|
8.01 (1.23, 14.85)*
|
8.02 (1.14, 14.87)*
|
|
ASEI
|
1218.32 (−2805.19, 5258.4)
|
946.37 (−3116.03, 4995.35)
|
|
Postictal Suppression Index
|
0.66 (−7.81, 9.3)
|
− 0.47 (−9.64, 8.71)
|
|
MSP
|
2833.84 (−3507.98, 9233.53)
|
1901.98 (−4242.33, 8021.26)
|
|
MSC
|
8.18 (1.88, 14.57)*
|
7.65 (1.24, 14.06)*
|
|
TtoPP
|
4.4 (0.25, 8.6)
|
3.46 (−0.53, 7.41)
|
|
TtoPC
|
14.08 (3.87, 24.88)*
|
14.67 (3.87, 26.08)*
|
(.) p=0.05–0.1; (*) p=0.01–0.05; (**) p=0.001–0.01; PSI: patient state index;
ASEI: Average seizure energy index; EEG: electroencephalogram; EEPRS:
ECT–EEG Parameter Rating Scale; HR: heart rate; TtoPC: time to peak
coherence; TtoPP: time to peak power; MSP: maximum sustained power; MSC:
maximum sustained coherence; SD: standard deviation.
The PSI was the only factor in both models that was positively and significantly
associated with better seizure quality according to the EEG phases, greater seizure
concordance, longer seizure time (both motor and electroencephalographic), and
higher values on the MSC index ([Table
4]). The PSI group obtained higher values than the control group in the
average maximum post-stimulus heart rate, the pre-post difference, and the number
of
occasions where the value of 140 beats/min was exceeded. None of these variables
reached significant differences between groups according to the linear models in
autonomic activation (see [Table 3],
supplementary data).
Discussion
The main findings of the present study are the association between the use of the
PSI
and the improvement in seizure quality assessed through electroencephalographic
recording and some of the parameters that are used as seizure indicators (duration
of motor and electroencephalographic seizure, seizure concordance, MSC). In
addition, our procedure required lower stimulation energy compared to the control
group. These results align with those obtained in studies that measured anesthetic
depth using other monitors [6]
[9]
[26].
Initially, one might think that the control group was at a disadvantage due to a
deeper level of anesthesia when applying the stimulus at a Ramsay scale score of 6.
However, this scale does not distinguish between levels of depth and those of
sedation, and therefore, the score alone does not confirm that the patients in the
control group had a higher level of narcosis than those in the PSI group [23]. The lack of PSI monitoring in the
control group prevents confirmation of the extent to which anesthetic depth differed
between the two groups when applying the electrical stimulus.
Unlike the study by Kranaster [6] using the
bispectral index, its use has not been found to be associated with an improvement
in
the postictal suppression index, although it was associated with seizure
concordance, which also reflects the inhibitory brain activity to end seizure [27]. The older age of the patients in our
sample explains this difference since age inversely affects the postictal
suppression index [26]
[28].
The results of the present study indicate a relationship between anesthetic depth
and
the MSC parameter, as in the studies by Kranaster et al. [6] and Gasteiger et al. [9]. This measure refers to the
synchronization of the seizure between both hemispheres, that is, one of the
parameters that, together with the postictal suppression index, has been proposed
as
a possible predictor of the response to ECT [29], since the interhemispheric coherence measured during the seizure can
be considered a reflection of its generalization [30]. A prolongation of TtoPC has been
observed and related to worse quality [19]. Similar results have been found using theophylline as a seizure
enhancer, yet the interpretation of these results is equivocal [29], although some authors have related
them with presenting longer seizures [31].
These data raise the question of whether the strategy used to improve seizure quality
has a specific effect only on some parameters that measure it, in the same way, that
the modifications made to improve the seizure threshold often differ from those that
prolong seizure duration [29]
[31]
[32], or for example, the observed influence of hyponatremia or the use of
theophylline alone using the MSC parameter [18]
[29].
Some authors, like Ingram et al. [33], have
considered automated parameters to be less reliable than a review of the EEG tracing
performed by an expert clinician due to the presence of artifacts in the electrical
signals. In this sense, the use of the PSI also achieved a better seizure expression
in the EEG.
Given that the EEG may have a limited capacity to determine seizure adequacy, a
patient’s heart rate may more accurately and significantly reflect the effectiveness
of ECT as it shows the diffusion of the seizure and the activation of deep brain
regions such as the diencephalon [34].
Thus, induced peak heart rate has also been considered in addition to the duration
and power of the seizures, interhemispheric coherence, and postictal suppression
[35]
[36]. We did not find a positive association
between the use of the PSI and this parameter. The attenuating effect of the
sympathetic response caused by propofol might limit a maximum post-stimulus heart
rate with higher values [37].
It is worth noting that the significant association of the use of the PSI precisely
occurred with some parameters related to the neurophysiological aspects proposed for
the antidepressant action of ECT (seizure concordance and interhemispheric
coherence) [27]. Although benzodiazepines
can affect seizure quality, it has been observed that the anticonvulsant effect of
the anesthetic can have a greater impact than psychotropic medication [26]. We observed a significant negative
association between the dose of propofol and the motor and electroencephalographic
seizure time. Conversely, the dose of lorazepam did not reach statistical
significance to be included in the correlation models. This finding differs from the
results obtained by Minelli et al. [36],
who found a negative effect of benzodiazepines because they affected synchrony
between hemispheres and post-stimulus tachycardia, especially in the unilateral ECT
modality. If this, in fact, happened, it would have disadvantaged the PSI group
because they had a greater number of RUL sessions.
As there are no previous studies presenting the ideal PSI value in ECT, a range
between 50 and 70 was used for stimulation based on the fact that the average values
for loss of consciousness in the PSI would be between 30 and 45, influenced by the
anesthetic protocol used and high interindividual variability [38]. The value of 50 was considered the
threshold between consciousness and non-consciousness [39]. In comparison with other monitors,
other authors have proposed a value>65 in the bispectral index [6] and>41 for
NarcotrendTM
[9] in ECT.
Therefore, this is an aspect that should be assessed in further research.
The lack of differences in clinical response with the HDRS-17 between the two groups
can be attributed to the fact that the score of this scale was used to determine
when the patient completed the study, decreasing the likelihood of detecting
differences in clinical response. Instead, other procedural variables of clinical
relevance (e. g., number of sessions, restimulations, stimulus charge used) may
differ between the two groups. Moreover, an adequate seizure does not ensure the
optimal treatment outcome, as the predictive value of ictal EEG parameters regarding
clinical outcomes is questioned [40], and
clinical factors influencing the response to ECT are also known [41]. Other authors have demonstrated that
delaying the application of the electrical stimulus relative to the administration
of the anesthetic agent—without using anesthetic depth monitoring—can improve
seizure quality, although there is no consensus on the optimal delay [42]. The use of anesthetic agents with less
anticonvulsant effect than propofol could improve seizure expression but would
reduce the utility of determining anesthetic depth.
Although this was a prospective and novel study addressing the use of the PSI during
ECT, several limitations should be considered, such as: this was not a double-blind
study; the values of the anesthetic depth indices are not yet standardized for
psychiatric populations, which may exhibit anomalies in EEG recording with respect
to the diagnosis or the use of psychotropic drugs that could interfere with the
determination of the PSI, and whose presence was not discarded prior to inclusion
in
the study (a baseline EEG recording could resolve this issue); analysis of the
evolution of HDRS-17 scores throughout treatment in each patient could show clinical
differences between the two groups; although the MEC has been widely used, more
sensitive neuropsychological tests could better detect differences in cognitive
adverse effects between the two groups; the use of propofol may limit the
extrapolation of these results to patients in whom another anesthetic agent is
used.
Notwithstanding, the findings of the present study, such as a lower stimulus load,
a
longer motor and electroencephalographic seizure time, a higher quality in the EEG
recording of the seizure, and higher MSC values, allowed us to conclude that the
measurement of the anesthetic depth using the PSI improved seizure quality and is
useful in determining the optimal time for applying the electrical stimulus compared
to the usual ECT. Our findings also enable us to conclude that this procedure can
maintain the efficacy of ECT, although it did not cause less cognitive
impairment.
