- Email: [email protected]
The effectiveness of BIS monitoring during electro-convulsive therapy: A systematic review and meta-analysis
Journal of Clinical Anesthesia 58 (2019) 100–104
Contents lists available at ScienceDirect
Journal of Clinical Anesthesia journal homepage: www.elsevier.com/locate/jclinane
Original Contribution
The effectiveness of BIS monitoring during electro-convulsive therapy: A systematic review and meta-analysis
T
Gilles Guerrier (MD, PhD) , Marc-Antoine Gianni (MD) ⁎
Department of Anesthesiology and Intensive Care, Cochin Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), France
ARTICLE INFO
ABSTRACT
Keywords: Anesthesia depth Electro-convulsive therapy Efficacy Bispectral index
Study objective: Electroconvulsive therapy (ECT) has been shown to be highly effective in patients suffering from treatment-resistant depression. ECT procedure is performed under general anesthesia but the impact of anesthesia depth on seizure characteristics and clinical outcome remains unclear. We aimed to study the effects of BIS monitoring on electric and clinical response to ECT treatment. Design: Meta-analysis searching PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO database, and Google Scholar. Patients/interventions: Studies comparing different BIS levels during ECT. Measurement: The primary outcome measured the electrical seizure duration. Secondary outcomes measured the clinical seizure duration, and correlation between pre-ictal BIS level and awakening time. Difference in means (MD) was used for effect size. Main results: Among 38 eligible studies, 7 were analyzed including 260 patients, aged from 16 to 80 years old, benefiting from 1283 ECT sessions. Higher BIS levels were associated with longer electric seizures duration (correlation 0.61, 95% CI [0.39–0.75], 7 studies) and longer motor seizures duration (correlation 0.72, 95% CI [0.29–0.91], 6 studies). Conclusions: High values of pre-ictal BIS are associated with improved seizure duration. The usefulness of systematic BIS monitoring during all ECT procedures should be further studied to better identify adequate BIS levels according to patient's characteristics.
1. Introduction Major depression is a leading cause of mental disorder affecting more than 350 million people worldwide [1]. Over a third of this population fails to respond to medications. Electroconvulsive therapy (ECT) has been shown to be highly effective in patients suffering from treatment-resistant depression [2–4]. To prevent seizure-related injuries potentially related to substantial muscle contractions (such as limb vertebral bodies fractures), ECT procedure is performed under muscle relaxation associated with general anesthesia. Electric characteristics of ECT-induced seizure have been associated with the procedure efficacy [5]. The nature and optimal dosage of hypnotic drugs are not clearly defined [6–9]. Despite its well documented anticonvulsant effect, propofol remains the most commonly used hypnotic agent for ECT [10]. The depth of anesthesia has been shown to impact seizure characteristics and level of stimulation energy delivered. Deep anesthesia may reduce the antidepressant effect of ECT [11], and increase the risk of cognitive side-effects [12]. Light anesthesia might
⁎
result in awareness [13] but leads to improved seizures quality [14]. In addition, cognitive impairments including memory disturbances correlated to deliver electric intensity may be impacted by depth of anesthesia [15,16]. As ECT is not only used in the treatment of depression, deep anesthesia may reduce not only the antidepressant effect of the therapy, but more generally speaking, the effect of the therapy. The risk of the cognitive side-effects is in connection with stimulation energy and not with the depth of the anesthesia per se. The objective of ECT is therefore to induce seizure with the minimum required electric intensity, fitting the condition of each patient, to treat specific psychiatric disorders. The monitoring of depth of anesthesia is achieved using a frontal electroencephalographic device called Bispectral Index (BIS) [17]. BIS values ranging from 40 to 60 are suggested to achieve adequate general anesthesia and avoid memorization. Titration of anesthetic drugs may be especially useful in ECT to optimize electrical and clinical responses and reduce side effects. Several individual observational studies performed have shown various results regarding the electrical benefits
Corresponding author at: Anesthésie-réanimation chirurgicale, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail address: [email protected] (G. Guerrier).
https://doi.org/10.1016/j.jclinane.2019.05.006 Received 26 December 2018; Received in revised form 27 April 2019; Accepted 1 May 2019 0952-8180/ © 2019 Elsevier Inc. All rights reserved.
Journal of Clinical Anesthesia 58 (2019) 100–104
G. Guerrier and M.-A. Gianni
Identification
PRISMA 2009 Flow Diagram
Records iden!fied through database searching (n=39)
Addi!onal records iden!fied through other sources (n=2)
Eligibility
Screening
Records a#er duplicates removed (n=38) Irrelevant (intervention) n=27 Abstract only n=130 Design (Review) n=132
Records screened (n=38)
Records excluded (n=29)
Full-text ar!cles assessed for eligibility (n=9)
Ver excluded, Full-text ar!cles with reasons (n=0)
Included
Studies included in qualita!ve synthesis (n=9)
Studies included in quan!ta!ve synthesis (meta-analysis) (n=7) Fig. 1. Search and selection process of studies.
provided by monitoring the depth of anesthesia during the procedure [18,19]. We performed a meta-analysis to investigate the correlation between depth of anesthesia and electric and motor response of ECT procedures.
2.1. Inclusion criteria Selected articles were read by the authors for potential inclusion in the final analysis. All studies providing data regarding different BIS levels during ECT monitoring were included. Studies that did not explicitly mentioned BIS levels during monitoring were individually considered before any statistical analyses. Studies with adults only (aged 16 ≥ yr) were included. The primary outcome was electrical seizure duration. Secondary outcomes were clinical seizure duration, correlation between pre-ictal BIS level and awakening time, and negative outcomes such as cognitive impairment and anesthesia complications. Pre-ictal BIS referred to BIS value right before the seizure. This study was performed according to the guidelines of the Metaanalysis of Observational Studies in Epidemiology group (MOOSE) including the presence of blinding of quality assessors, data regarding study withdrawals, stratification or regression on predictors of study results [20]. One point was awarded for each criterion; no points were awarded if no data were provided regarding the methodology of these procedures. The maximum score that could be attributed to a trial was three.
2. Materials and methods The National Library of Medicine's MEDLINE database, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO database, and the Database of Abstracts of Reviews of Effects as well as Google Scholar (“other sources”, Fig. 1) were searched from 1966 to March 2019. No language restrictions were used. MESH terms electroconvulsive therapy (n = 14,116), sismotherapy (n = 14), and seizure therapy (n = 58,584), and were combined with the term OR. Text word Bispectral (n = 2833), MESH term electroencephalography (n = 140,960), and text word BIS (n = 90,055) were combined with the term OR. The two searches were combined with the term AND and were limited by Human and Clinical trials (n = 12,166). 101
Journal of Clinical Anesthesia 58 (2019) 100–104
G. Guerrier and M.-A. Gianni
2.2. Statistical analysis
Table 2 Studies excluded for other reasons than irrelevant intervention or topic.
This correlation meta-analysis was performed using a random effects model for heterogeneity. A p-value of 0.05 was the level of significance, and variances were considered to be unequal. Study results were pooled and correlation coefficients were extracted from each study result section. If not available, correlation coefficients were derivated and calculated from data reported in the study. Means and standard deviations (SDs) were calculated with the inverse variance method. The Hedges-Olkin method was used to pool and weight correlation coefficients through a Fisher Z transformation. All statistical analyses were performed using the Comprehensive Meta-Analysis Software (Version 3.3.070). When relevant, a funnel plot to assess publication bias for comparisons of more than five trials was generated. Heterogeneity was assessed by visual inspection of graphs and using the I2 result. No subgroup analyses were performed in order to avoid spurious findings. Outcomes with statistical heterogeneity were described using a qualitative approach. Heterogeneity was explained by exploring difference in anesthetic drugs, and different time points to outcome measurement.
BIS level and seizure quality (thiopental) BIS level and seizure length (thiopental) BIS value at time points (methohexital) Correlations between seizure duration and plasma and effectsite concentrations (thiopental) BIS level and seizure quality (thiopental) BIS value at time points (propofol) BIS value at time points (propofol)
Sartorius [25] Nishihara [26] Gombar [27]
Abstract available only Not enough statistical data provided for quantitative analysis Not enough statistical data provided for quantitative analysis Review
High pre-ictal BIS values may be associated with improved seizure duration suggesting the usefulness of systematic BIS monitoring during all ECT procedures. This finding is in line with already observed time–response effects in ECT performed under general anesthesia. However, appropriate dosage of anesthetic drugs for ECT remains a clinical challenge, especially in depressed patients experiencing recurrences. Since routine practice requires drugs administration to achieve immobility, this clinical practice may induce a concerning overdose for hypnosis. Moreover, increasingly large doses of general anesthesia are required to provide hypnosis [31]. While BIS has been validated as a measure anesthesia depth, the competence to precisely dose general anesthetic towards a targeted hypnosis level well explains the increase of seizure duration. In addition, higher BIS procedures may reduce the incidence and magnitude of cognitive impairments effects after ECT by reducing the level of delivered electric intensity. This may be an invaluable benefit in itself because reports indicate that cognitive impairments are the primary patient concern during the post-procedure period [32]. Although negative outcomes were not reported in this meta-analysis, one can assume a lighter anesthesia may result in lower complications rate, including aspiration rate, awakening time, post-ECT cognitive impairment and adverse memory effects. A recent review suggests anesthetic variables have a significant impact on the success of the procedure and patient tolerance of ECT [33], including type of induction agent, hyperventilation, and optimizing anesthesia-ECT time interval optimization. A ketamine-propofol combination with or without adjuvants such as dexmedetomidine or remifentanil may aid in augmentation of ECT efficacy; however, they are not recommended routinely and not compatible with a BIS monitoring. In particular, BIS has a less pronounced response compared with propofol, after the administration of ketamine [34]. Along anesthetic procedures, standardization of ECT technical aspects should also be explored. This meta-analysis has several major limitations. First, all selected studies were observational with a low-quality score assessment, suggesting potential bias including information and selection bias. Studies may have been affected by a misclassification bias linked to the observer effect overestimating the benefit of higher BIS procedures compared with the standard procedure. However, two studies [25,26] reporting a blinded assessment had the highest correlation coefficient regarding our primary outcome. Second, despite the comprehensive search, published or unpublished reports or trials could have been missed. Third, the paucity of studies in each category precluded the assessment of publication bias. Fourth, BIS values may have been inaccurate since they were recorded during a procedure using muscle relaxing drugs known for interfering with BIS results [35]. In addition, drugs used may not allow providing precise BIS values, including succinylcholine and methohexital [36]. In particular, as methohexital activates the EEG and increases the BIS, it may be that methohexital is providing the benefit and not the higher BIS number. However, the effect is the same if one looking at patients receiving propofol only. Accurate BIS recording requires a minimal duration of anesthesia stable
Table 1 Studies included in quantitative analysis (meta analysis).
Kranaster [21] Choe [22] White [23] Ochiai [24]
Miyazaki [29] Lemmens [28] Cai-Cai [30] Stripp [18]
4. Discussion
Among 38 eligible studies (Fig. 1), seven observational studies were finally included in the study (Table 1). Data from 260 patients, aged from 16 to 80 years old (mean age 40 yo), benefiting from 1283 ECT sessions, were analyzed. Causes for exclusion are reported in Table 2. Trial characteristics are summarised in Table 3. No reviews regarding BIS in ECT were found in The Cochrane Library or in Medline. Sample sizes were small in all included studies (ranging from eight to 118 subjects). All studies included patients with depression, with the exception of two patients with a schizophrenic disorder diagnosed according to DSM-IV. Anesthetic procedure was detailed in all studies. The most commonly hypnotic drugs used were propofol and etomidate, with succinylcholine being the muscle relaxant drug administered in all studies. All included studies were monocentric [21–27], while outcome assessment was blinded in three studies [25–27]. (See Table 4.) The mean pre-ictal BIS ranged from 35 to 64. Higher BIS level increased both electric seizures duration (correlation 0.61 95% CI, [0.39–0.75], seven studies, Table 5) and motor seizures duration (correlation 0.72, 95% CI [0.29–0.91], six studies, Table 6). The results showed significant heterogeneity between studies according to an I2 value superior to 75%. No significant correlation between BIS level and awakening time was found among the two studies reporting this outcome [23,27] (Table 7). BIS value was not found to be associated with the number of ECT treatments administered. Short term or long terms clinical outcome (measured at specific time points described by investigators) included relapse rates were not assessed in any of the selected studies. A single study reported the correlation between the number of ECT sessions required to achieve satisfactory clinical response and the mean pre-ictal BIS [23]. A low-quality score was reported among studies included in the quantitative meta-analysis: four trials had a score of zero [21–24], and
Primary outcome (with detailed anesthetic drug used)
Reason for exclusion
three trials had a score of one [25–27]. The funnel plot was examined for electric and motor seizure duration only. There were five studies or less providing data regarding other relevant outcomes.
3. Results
Study
Study
102
Journal of Clinical Anesthesia 58 (2019) 100–104
G. Guerrier and M.-A. Gianni
Table 3 Characteristics of included studies. Study
Number of ECT
Number of participants
869 30 100 100 46 38 100
118 30 25 16 8 38 25
Kranaster [21] Choe [22] White [23] Ochiai [24] Sartorius [25] Nishihara [26] Gombar [27]
Study design Retrospective Prospective observational Prospective observational Prospective observational Prospective observational Prospective observational Prospective observational
Table 4 Outcome characteristics. Targeted pre-ictal BIS
Mean BIS nadir
Mean pre-ictal BIS
Mean BIS baseline
65 Not assessed Not assessed 55 Not assessed Not assessed 47
Not described Not described 28 Not described Not described 46 31
64 52 35 58 Not described 54 50
Not described 95 95 90 Not described 92 91
Kranaster [21] Choe [22] White [23] Ochiai [24] Sartorius [25] Nishihara [26] Gombar [27]
Mean EEG seizure duration
Mean motor seizure duration
Average awakening BIS
Stimulus intensity
47 30 54 Not described Not described 39 34
27 26 38 Not described Not described 29 Not described
Not described 48 50 62 Not described 45 52
Not described Not described Not described 110 V Not described 106 V 100mCo
Kranaster [21] Choe [22] White [23] Ochiai [24] Sartorius [25] Nishihara [26] Gombar [27]
Table 5 Correlation pooled between BIS level and electric seizure duration, random effect, 95% CI. Study
Sample size
Correlation
Lower limit
Upper limit
Z
p
Kranaster [21] Choe [22] White [23] Ochiai [24] Gombar [27] Sartorius [25] Nishihara [26] Gombar [27] Pooled results
869 30 100 100 100 46 38 100
0.26 0.6 0.4 0.73 0.736 0.67 0.73 0.736 0.607
0.197 0.306 0.221 0.623 0.631 0.471 0.535 0.631 0.397
0.321 0.79 0.553 0.81 0.815 0.804 0.851 0.815 0.756
7.831 3.602 4.172 9.147 9.275 5.316 5.494 9.275 0.756
0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001
Table 6 Correlation pooled between BIS level and motor measured seizure duration, random effect, 95% CI. Study
Sample size
Correlation
Lower limit
Upper limit
Z
p
Kranaster [24] Choe [25] White [26] Ochiai [27] Nishihara [26] Gombar [27] Pooled results
869 30 100 100 38 100
0.17 0.69 0.3 0.59 0.707 0.99 0.724
0.105 0.475 0.11 0.292 0.593 0.982 0.292
0.234 0.827 0.469 0.784 0.793 0.994 0.911
5.052 5.017 3.048 3.521 8.678 17.355 2.916
0.001 0.001 0.002 0.001 0.001 0.001 0.004
Table 7 Correlation pooled between higher BIS level and awakening time, random effect, 95% CI. Study
Sample size
Correlation
Lower limit
Upper limit
Z
p
White [23] Gombar [27] Final
100 100
0.5 −0.397 0.065
0.337 −0.55 −0.709
0.634 −0.218 0.768
5.41 −4.137 0.133
0.001 0.001 0.894
103
Journal of Clinical Anesthesia 58 (2019) 100–104
G. Guerrier and M.-A. Gianni
phase uneasily achieved with this short acting muscle relaxant drug. There is a delay of anywhere between 24 s and 120 s between the time that the BIS number is displayed and the actual time the BIS level should be capture and analyzed [37]. Moreover, a significant proportion of patients who have received a course of ECT may have BIS values in the anesthetised range even when they are awake. BIS values of awake individuals in resting state drop significantly through a course of bi-temporal brief-pulse ECT [38]. The BIS may thus not provide accurate estimation of the depth of anesthesia during ECT after the initial ECT sessions. Finally, a clinical outcome would have been much more relevant to analyze the benefit of BIS monitoring. However, this data was not available in the included studies. The findings of this metaanalysis should therefore be interpreted with caution with regard to applicability to all patients. Although ECT is an evidence-based psychiatric treatment, in which generalised convulsions should be induced using the minimum electric intensity, the lack of standardization for anesthesic procedures should be urgently addressed. The use of BIS monitoring has not yet been proposed widely to provide helpful benefits, including reducing the number of ECT sessions to achieve satisfactory clinical response, and subsequent reduced time spent in hospital. So far, BIS monitoring alone may not be relied upon for timing stimulus. Innovative anesthetic protocols in synergy with standardized ECT procedures must be developed. Large, well designed and methodologically rigorous trials are needed to compare different depth of anesthesia. Identifying the adequate BIS target for ECT may contribute to optimize the treatment efficacy, improve the cognitive tolerance, and reduce relapse rates.
[11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]
Disclosures
[25]
No funding has been received to perform this study.
[26]
Declaration of interest
[27]
None.
[28]
Disclosure of funding
[29]
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
[30]
References
[31]
[1] Murray CJL, Lopez AD. The global burden of disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Harvard University Press; 1996. [2] Husain MM, Rush AJ, Fink M. Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a consortium for research in ECT (CORE) report. J Clin Psy 2004;65:485–91. [3] Sackeim HA, Prudic J, Devanand DP. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. New Engl J Med 1993;328:839–46. [4] Lisanby SH. Electroconvulsive therapy for depression. New Engl J Med 2007;357:1939–45. [5] Perera TD, Luber B, Nobler MS. Seizure expression during electro-convulsive therapy: relationships with clinical outcome and cognitive side effects. Neuropsychopharmacol 2004;29:813–25. [6] De Baerdemaeker L, Audenaert K, Peremans K. Anaesthesia for patients with mood disorders. Curr Opin Anaesth 2005;18:333–8. [7] Deiner S, Frost EA. Electroconvulsive therapy and anaesthesia. Int Anesth Clin 2009;47:81–92. [8] Singh PM, Arora S, Borle A, Varma P, Trikha A, Goudra BG. Evaluation of etomidate for seizure duration in electroconvulsivotherapy: a systematic review and metaanalysis. J ECT 2015;31:213–25. [9] MacPherson RD, Loo CK. Cognitive impairment following electroconvulsive therapy — does the choice of anesthetic agent make a difference? J ECT 2008;24:52–6. [10] Bundy BD, Hewer W, Andres FJ, Gass P, Sartorius A. Influence of anesthetic drugs
[32] [33] [34]
[35] [36] [37]
[38]
104
and concurrent psychiatric medication on seizure adequacy during electroconvulsive therapy. J Clin Psychiatry 2010;71:775–7. Sartorius A, Munoz Canales EM, Krumm B. ECT anaesthesia: the lighter the better? Pharmacopsychatry 2006;39:201–4. Boylan LS, Haskett RF, Mulsant BH. Determinants of seizure threshold in ECT: benzodiazepine use, anesthetic dosage, andother factors. J ECT 2000;16:3–18. Andrade C, Thirthalli J, Gangadhar BN. Unilateral non-dominant electrode placement as a risk factor for recall of awareness under anaesthesia during electroconvulsive therapy. J ECT 2007;23:201–3. Sartorius A, Krier A, Andres FJ, Bender HJ, Krumm B, Henn FA. Bi-spectral index monitoring for more effective electroconvulsive therapy? Br J Anaesth 2006;96:806–7. Sackeim HA, Prudic J, Fuller R, Keilp J, Lavori PW, Olfson M. The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacol 2007;32:244–54. Lisanby SH, Maddox JH, Prudic J, Devanand DP, Sackeim HA. The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry 2000;57:581–90. Rosow C, Manberg PJ. Bispectral index monitoring. Anaesthesiology Clinical North America 1998;2:89–107. Stripp T, Jorgensen M, Olsen N. Anaesthesia for electroconvulsive therapy - new tricks for old drugs: a systematic review. Acta Neuropsychiatry 2017(2):1–9. Kayser S, Bewernick BH, Soehle M, Switala C, Gippert SM, Dreimueller N, et al. Degree of postictal suppression depends on seizure induction time in magnetic seizure therapy and electro- convulsive therapy. J ECT 2017;33:167–75. Stroup DF, Berlin JA, Morton SC. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283:2008–12. Kranaster L, Hoyer C, Janke C. Bispectral index monitoring and seizure quality optimization in electroconvulsive therapy. Pharmacopsychiatry 2013;46:147–50. Choe Y, Lee S, Lee K, Cheong S, Kim Y, Shin C, et al. Correlation between pre-ictal bispectral index and seizure duration during electroconvulsive therapy under thiopental anaesthesia. Korean J Anesth 2003;45:693–6. White P, Rawal S, Recart A, Thornton L, Litle L, Stool L. Can the bispectral index be used to predict seizure time and awakening after electroconvulsive therapy? Anesth Analg 2003;96:1636–9. Ochiai R, Yamada T, Kiyama S, Nakaoji T, Takeda J. Bispectral index as an indicator of seizure inducibility in electroconvulsive therapy under thiopental anesthesia. Anesth Analg 2004;98:1030–5. Sartorius A, Krier A, Andres F, Bender H, Krumm B, Henn F. Bispectral index monitoring for more effective electroconvulsive therapy? Br J Anaesth 2006;96:806–7. Nishihara F, Saito S. Pre-ictal bispectral index has a positive correlation with seizure duration during electroconvulsive therapy. Anesth Analg 2002;94:1249–52. Gombar S, Aggarwal D, Khanna A, Gombar K, Chavan B. The bispectral electroencephalogram during modified electroconvulsive therapy under propofol anesthesia-relation with seizure duration and awakening. J ECT 2011;27:114–8. Lemmens H, Levi D, Debattista C, Brock-Utne J. The timing of electroconvulsive therapy and bispectral index after anesthesia induction using different drugs does not affect seizure duration. J Clin Anesth 2003;15:29–32. Miyazaki S, Muratani T, Morimoto K, Shimizu S, Tanaka M, Minami T. Relationship between seizure duration and bispectral index during modified electroconvulsive therapy. Masui 2006;55:1222–4. Cai Cai L, Qian X, An J, Yu Z, Wu J, Wen H, et al. Electroconvulsive therapy under general anaesthesia with cisatracurium, laryngeal mask airways, and bispectral index. J ECT 2016;32:17–9. Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, Gambus PL, et al. Propofol dosing regimens for ICU sedation based upon an integrated pharmacokineticpharmacodynamic model. Anesthesiology 2001;95:324–33. Rami-Gonzajez L, Bernardo M, Boget T, Gil-Verona JA, Salamero M, Junque C. Subtypes of memory dysfunction associated with ECT: characteristics and neurobiological bases. J ECT 2001;17:129–35. Kadiyala PK, Kadiyala LD. ECT: a new look at an old friend. Curr Opin Anaesthesiol 2018;31:453–8. Vereecke HE, Vanluchene AL, Mortier EP, Everaert K, Struys MM. The effects of ketamine and rocuronium on the A-line auditory evoked potential index, bispectral index, and spectral entropy monitor during steady state propofol and remifentanil anesthesia. Anesthesiology 2006;105:1122–34. Schuller PJ, Newell S, Strickland PA, Barry JJ. Response of bispectral index to neuromuscular block in awake volunteers. Br J Anaesth 2015;115(Suppl. 1):i95–103. Miner JR, Biros MH, Heegaard W, Plummer D. Bispectral electroencephalographic analysis of patients undergoing procedural sedation in the emergency department. Acad Emerg Med 2003;10:638–43. Zanner R, Pilge S, Kochs EF, Kreuzer M, Schneider G. Time delay of electroencephalogram index calculation: analysis of cerebral state, bispectral, and Narcotrend indices using perioperatively recorded electroencephalographic signals. Br J Anaesth 2009;103:394–9. Thimmaiah R. Effect of a course of electroconvulsive therapy on interictal bispectral index values a prospective study. J ECT 2012;28:20–3.
Contents lists available at ScienceDirect
Journal of Clinical Anesthesia journal homepage: www.elsevier.com/locate/jclinane
Original Contribution
The effectiveness of BIS monitoring during electro-convulsive therapy: A systematic review and meta-analysis
T
Gilles Guerrier (MD, PhD) , Marc-Antoine Gianni (MD) ⁎
Department of Anesthesiology and Intensive Care, Cochin Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), France
ARTICLE INFO
ABSTRACT
Keywords: Anesthesia depth Electro-convulsive therapy Efficacy Bispectral index
Study objective: Electroconvulsive therapy (ECT) has been shown to be highly effective in patients suffering from treatment-resistant depression. ECT procedure is performed under general anesthesia but the impact of anesthesia depth on seizure characteristics and clinical outcome remains unclear. We aimed to study the effects of BIS monitoring on electric and clinical response to ECT treatment. Design: Meta-analysis searching PubMed, Web of Science, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO database, and Google Scholar. Patients/interventions: Studies comparing different BIS levels during ECT. Measurement: The primary outcome measured the electrical seizure duration. Secondary outcomes measured the clinical seizure duration, and correlation between pre-ictal BIS level and awakening time. Difference in means (MD) was used for effect size. Main results: Among 38 eligible studies, 7 were analyzed including 260 patients, aged from 16 to 80 years old, benefiting from 1283 ECT sessions. Higher BIS levels were associated with longer electric seizures duration (correlation 0.61, 95% CI [0.39–0.75], 7 studies) and longer motor seizures duration (correlation 0.72, 95% CI [0.29–0.91], 6 studies). Conclusions: High values of pre-ictal BIS are associated with improved seizure duration. The usefulness of systematic BIS monitoring during all ECT procedures should be further studied to better identify adequate BIS levels according to patient's characteristics.
1. Introduction Major depression is a leading cause of mental disorder affecting more than 350 million people worldwide [1]. Over a third of this population fails to respond to medications. Electroconvulsive therapy (ECT) has been shown to be highly effective in patients suffering from treatment-resistant depression [2–4]. To prevent seizure-related injuries potentially related to substantial muscle contractions (such as limb vertebral bodies fractures), ECT procedure is performed under muscle relaxation associated with general anesthesia. Electric characteristics of ECT-induced seizure have been associated with the procedure efficacy [5]. The nature and optimal dosage of hypnotic drugs are not clearly defined [6–9]. Despite its well documented anticonvulsant effect, propofol remains the most commonly used hypnotic agent for ECT [10]. The depth of anesthesia has been shown to impact seizure characteristics and level of stimulation energy delivered. Deep anesthesia may reduce the antidepressant effect of ECT [11], and increase the risk of cognitive side-effects [12]. Light anesthesia might
⁎
result in awareness [13] but leads to improved seizures quality [14]. In addition, cognitive impairments including memory disturbances correlated to deliver electric intensity may be impacted by depth of anesthesia [15,16]. As ECT is not only used in the treatment of depression, deep anesthesia may reduce not only the antidepressant effect of the therapy, but more generally speaking, the effect of the therapy. The risk of the cognitive side-effects is in connection with stimulation energy and not with the depth of the anesthesia per se. The objective of ECT is therefore to induce seizure with the minimum required electric intensity, fitting the condition of each patient, to treat specific psychiatric disorders. The monitoring of depth of anesthesia is achieved using a frontal electroencephalographic device called Bispectral Index (BIS) [17]. BIS values ranging from 40 to 60 are suggested to achieve adequate general anesthesia and avoid memorization. Titration of anesthetic drugs may be especially useful in ECT to optimize electrical and clinical responses and reduce side effects. Several individual observational studies performed have shown various results regarding the electrical benefits
Corresponding author at: Anesthésie-réanimation chirurgicale, Hôpital Cochin, 27 rue du Faubourg Saint-Jacques, 75014 Paris, France. E-mail address: [email protected] (G. Guerrier).
https://doi.org/10.1016/j.jclinane.2019.05.006 Received 26 December 2018; Received in revised form 27 April 2019; Accepted 1 May 2019 0952-8180/ © 2019 Elsevier Inc. All rights reserved.
Journal of Clinical Anesthesia 58 (2019) 100–104
G. Guerrier and M.-A. Gianni
Identification
PRISMA 2009 Flow Diagram
Records iden!fied through database searching (n=39)
Addi!onal records iden!fied through other sources (n=2)
Eligibility
Screening
Records a#er duplicates removed (n=38) Irrelevant (intervention) n=27 Abstract only n=130 Design (Review) n=132
Records screened (n=38)
Records excluded (n=29)
Full-text ar!cles assessed for eligibility (n=9)
Ver excluded, Full-text ar!cles with reasons (n=0)
Included
Studies included in qualita!ve synthesis (n=9)
Studies included in quan!ta!ve synthesis (meta-analysis) (n=7) Fig. 1. Search and selection process of studies.
provided by monitoring the depth of anesthesia during the procedure [18,19]. We performed a meta-analysis to investigate the correlation between depth of anesthesia and electric and motor response of ECT procedures.
2.1. Inclusion criteria Selected articles were read by the authors for potential inclusion in the final analysis. All studies providing data regarding different BIS levels during ECT monitoring were included. Studies that did not explicitly mentioned BIS levels during monitoring were individually considered before any statistical analyses. Studies with adults only (aged 16 ≥ yr) were included. The primary outcome was electrical seizure duration. Secondary outcomes were clinical seizure duration, correlation between pre-ictal BIS level and awakening time, and negative outcomes such as cognitive impairment and anesthesia complications. Pre-ictal BIS referred to BIS value right before the seizure. This study was performed according to the guidelines of the Metaanalysis of Observational Studies in Epidemiology group (MOOSE) including the presence of blinding of quality assessors, data regarding study withdrawals, stratification or regression on predictors of study results [20]. One point was awarded for each criterion; no points were awarded if no data were provided regarding the methodology of these procedures. The maximum score that could be attributed to a trial was three.
2. Materials and methods The National Library of Medicine's MEDLINE database, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, PsycINFO database, and the Database of Abstracts of Reviews of Effects as well as Google Scholar (“other sources”, Fig. 1) were searched from 1966 to March 2019. No language restrictions were used. MESH terms electroconvulsive therapy (n = 14,116), sismotherapy (n = 14), and seizure therapy (n = 58,584), and were combined with the term OR. Text word Bispectral (n = 2833), MESH term electroencephalography (n = 140,960), and text word BIS (n = 90,055) were combined with the term OR. The two searches were combined with the term AND and were limited by Human and Clinical trials (n = 12,166). 101
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2.2. Statistical analysis
Table 2 Studies excluded for other reasons than irrelevant intervention or topic.
This correlation meta-analysis was performed using a random effects model for heterogeneity. A p-value of 0.05 was the level of significance, and variances were considered to be unequal. Study results were pooled and correlation coefficients were extracted from each study result section. If not available, correlation coefficients were derivated and calculated from data reported in the study. Means and standard deviations (SDs) were calculated with the inverse variance method. The Hedges-Olkin method was used to pool and weight correlation coefficients through a Fisher Z transformation. All statistical analyses were performed using the Comprehensive Meta-Analysis Software (Version 3.3.070). When relevant, a funnel plot to assess publication bias for comparisons of more than five trials was generated. Heterogeneity was assessed by visual inspection of graphs and using the I2 result. No subgroup analyses were performed in order to avoid spurious findings. Outcomes with statistical heterogeneity were described using a qualitative approach. Heterogeneity was explained by exploring difference in anesthetic drugs, and different time points to outcome measurement.
BIS level and seizure quality (thiopental) BIS level and seizure length (thiopental) BIS value at time points (methohexital) Correlations between seizure duration and plasma and effectsite concentrations (thiopental) BIS level and seizure quality (thiopental) BIS value at time points (propofol) BIS value at time points (propofol)
Sartorius [25] Nishihara [26] Gombar [27]
Abstract available only Not enough statistical data provided for quantitative analysis Not enough statistical data provided for quantitative analysis Review
High pre-ictal BIS values may be associated with improved seizure duration suggesting the usefulness of systematic BIS monitoring during all ECT procedures. This finding is in line with already observed time–response effects in ECT performed under general anesthesia. However, appropriate dosage of anesthetic drugs for ECT remains a clinical challenge, especially in depressed patients experiencing recurrences. Since routine practice requires drugs administration to achieve immobility, this clinical practice may induce a concerning overdose for hypnosis. Moreover, increasingly large doses of general anesthesia are required to provide hypnosis [31]. While BIS has been validated as a measure anesthesia depth, the competence to precisely dose general anesthetic towards a targeted hypnosis level well explains the increase of seizure duration. In addition, higher BIS procedures may reduce the incidence and magnitude of cognitive impairments effects after ECT by reducing the level of delivered electric intensity. This may be an invaluable benefit in itself because reports indicate that cognitive impairments are the primary patient concern during the post-procedure period [32]. Although negative outcomes were not reported in this meta-analysis, one can assume a lighter anesthesia may result in lower complications rate, including aspiration rate, awakening time, post-ECT cognitive impairment and adverse memory effects. A recent review suggests anesthetic variables have a significant impact on the success of the procedure and patient tolerance of ECT [33], including type of induction agent, hyperventilation, and optimizing anesthesia-ECT time interval optimization. A ketamine-propofol combination with or without adjuvants such as dexmedetomidine or remifentanil may aid in augmentation of ECT efficacy; however, they are not recommended routinely and not compatible with a BIS monitoring. In particular, BIS has a less pronounced response compared with propofol, after the administration of ketamine [34]. Along anesthetic procedures, standardization of ECT technical aspects should also be explored. This meta-analysis has several major limitations. First, all selected studies were observational with a low-quality score assessment, suggesting potential bias including information and selection bias. Studies may have been affected by a misclassification bias linked to the observer effect overestimating the benefit of higher BIS procedures compared with the standard procedure. However, two studies [25,26] reporting a blinded assessment had the highest correlation coefficient regarding our primary outcome. Second, despite the comprehensive search, published or unpublished reports or trials could have been missed. Third, the paucity of studies in each category precluded the assessment of publication bias. Fourth, BIS values may have been inaccurate since they were recorded during a procedure using muscle relaxing drugs known for interfering with BIS results [35]. In addition, drugs used may not allow providing precise BIS values, including succinylcholine and methohexital [36]. In particular, as methohexital activates the EEG and increases the BIS, it may be that methohexital is providing the benefit and not the higher BIS number. However, the effect is the same if one looking at patients receiving propofol only. Accurate BIS recording requires a minimal duration of anesthesia stable
Table 1 Studies included in quantitative analysis (meta analysis).
Kranaster [21] Choe [22] White [23] Ochiai [24]
Miyazaki [29] Lemmens [28] Cai-Cai [30] Stripp [18]
4. Discussion
Among 38 eligible studies (Fig. 1), seven observational studies were finally included in the study (Table 1). Data from 260 patients, aged from 16 to 80 years old (mean age 40 yo), benefiting from 1283 ECT sessions, were analyzed. Causes for exclusion are reported in Table 2. Trial characteristics are summarised in Table 3. No reviews regarding BIS in ECT were found in The Cochrane Library or in Medline. Sample sizes were small in all included studies (ranging from eight to 118 subjects). All studies included patients with depression, with the exception of two patients with a schizophrenic disorder diagnosed according to DSM-IV. Anesthetic procedure was detailed in all studies. The most commonly hypnotic drugs used were propofol and etomidate, with succinylcholine being the muscle relaxant drug administered in all studies. All included studies were monocentric [21–27], while outcome assessment was blinded in three studies [25–27]. (See Table 4.) The mean pre-ictal BIS ranged from 35 to 64. Higher BIS level increased both electric seizures duration (correlation 0.61 95% CI, [0.39–0.75], seven studies, Table 5) and motor seizures duration (correlation 0.72, 95% CI [0.29–0.91], six studies, Table 6). The results showed significant heterogeneity between studies according to an I2 value superior to 75%. No significant correlation between BIS level and awakening time was found among the two studies reporting this outcome [23,27] (Table 7). BIS value was not found to be associated with the number of ECT treatments administered. Short term or long terms clinical outcome (measured at specific time points described by investigators) included relapse rates were not assessed in any of the selected studies. A single study reported the correlation between the number of ECT sessions required to achieve satisfactory clinical response and the mean pre-ictal BIS [23]. A low-quality score was reported among studies included in the quantitative meta-analysis: four trials had a score of zero [21–24], and
Primary outcome (with detailed anesthetic drug used)
Reason for exclusion
three trials had a score of one [25–27]. The funnel plot was examined for electric and motor seizure duration only. There were five studies or less providing data regarding other relevant outcomes.
3. Results
Study
Study
102
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Table 3 Characteristics of included studies. Study
Number of ECT
Number of participants
869 30 100 100 46 38 100
118 30 25 16 8 38 25
Kranaster [21] Choe [22] White [23] Ochiai [24] Sartorius [25] Nishihara [26] Gombar [27]
Study design Retrospective Prospective observational Prospective observational Prospective observational Prospective observational Prospective observational Prospective observational
Table 4 Outcome characteristics. Targeted pre-ictal BIS
Mean BIS nadir
Mean pre-ictal BIS
Mean BIS baseline
65 Not assessed Not assessed 55 Not assessed Not assessed 47
Not described Not described 28 Not described Not described 46 31
64 52 35 58 Not described 54 50
Not described 95 95 90 Not described 92 91
Kranaster [21] Choe [22] White [23] Ochiai [24] Sartorius [25] Nishihara [26] Gombar [27]
Mean EEG seizure duration
Mean motor seizure duration
Average awakening BIS
Stimulus intensity
47 30 54 Not described Not described 39 34
27 26 38 Not described Not described 29 Not described
Not described 48 50 62 Not described 45 52
Not described Not described Not described 110 V Not described 106 V 100mCo
Kranaster [21] Choe [22] White [23] Ochiai [24] Sartorius [25] Nishihara [26] Gombar [27]
Table 5 Correlation pooled between BIS level and electric seizure duration, random effect, 95% CI. Study
Sample size
Correlation
Lower limit
Upper limit
Z
p
Kranaster [21] Choe [22] White [23] Ochiai [24] Gombar [27] Sartorius [25] Nishihara [26] Gombar [27] Pooled results
869 30 100 100 100 46 38 100
0.26 0.6 0.4 0.73 0.736 0.67 0.73 0.736 0.607
0.197 0.306 0.221 0.623 0.631 0.471 0.535 0.631 0.397
0.321 0.79 0.553 0.81 0.815 0.804 0.851 0.815 0.756
7.831 3.602 4.172 9.147 9.275 5.316 5.494 9.275 0.756
0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001 0.001
Table 6 Correlation pooled between BIS level and motor measured seizure duration, random effect, 95% CI. Study
Sample size
Correlation
Lower limit
Upper limit
Z
p
Kranaster [24] Choe [25] White [26] Ochiai [27] Nishihara [26] Gombar [27] Pooled results
869 30 100 100 38 100
0.17 0.69 0.3 0.59 0.707 0.99 0.724
0.105 0.475 0.11 0.292 0.593 0.982 0.292
0.234 0.827 0.469 0.784 0.793 0.994 0.911
5.052 5.017 3.048 3.521 8.678 17.355 2.916
0.001 0.001 0.002 0.001 0.001 0.001 0.004
Table 7 Correlation pooled between higher BIS level and awakening time, random effect, 95% CI. Study
Sample size
Correlation
Lower limit
Upper limit
Z
p
White [23] Gombar [27] Final
100 100
0.5 −0.397 0.065
0.337 −0.55 −0.709
0.634 −0.218 0.768
5.41 −4.137 0.133
0.001 0.001 0.894
103
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phase uneasily achieved with this short acting muscle relaxant drug. There is a delay of anywhere between 24 s and 120 s between the time that the BIS number is displayed and the actual time the BIS level should be capture and analyzed [37]. Moreover, a significant proportion of patients who have received a course of ECT may have BIS values in the anesthetised range even when they are awake. BIS values of awake individuals in resting state drop significantly through a course of bi-temporal brief-pulse ECT [38]. The BIS may thus not provide accurate estimation of the depth of anesthesia during ECT after the initial ECT sessions. Finally, a clinical outcome would have been much more relevant to analyze the benefit of BIS monitoring. However, this data was not available in the included studies. The findings of this metaanalysis should therefore be interpreted with caution with regard to applicability to all patients. Although ECT is an evidence-based psychiatric treatment, in which generalised convulsions should be induced using the minimum electric intensity, the lack of standardization for anesthesic procedures should be urgently addressed. The use of BIS monitoring has not yet been proposed widely to provide helpful benefits, including reducing the number of ECT sessions to achieve satisfactory clinical response, and subsequent reduced time spent in hospital. So far, BIS monitoring alone may not be relied upon for timing stimulus. Innovative anesthetic protocols in synergy with standardized ECT procedures must be developed. Large, well designed and methodologically rigorous trials are needed to compare different depth of anesthesia. Identifying the adequate BIS target for ECT may contribute to optimize the treatment efficacy, improve the cognitive tolerance, and reduce relapse rates.
[11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]
Disclosures
[25]
No funding has been received to perform this study.
[26]
Declaration of interest
[27]
None.
[28]
Disclosure of funding
[29]
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
[30]
References
[31]
[1] Murray CJL, Lopez AD. The global burden of disease: A comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Harvard University Press; 1996. [2] Husain MM, Rush AJ, Fink M. Speed of response and remission in major depressive disorder with acute electroconvulsive therapy (ECT): a consortium for research in ECT (CORE) report. J Clin Psy 2004;65:485–91. [3] Sackeim HA, Prudic J, Devanand DP. Effects of stimulus intensity and electrode placement on the efficacy and cognitive effects of electroconvulsive therapy. New Engl J Med 1993;328:839–46. [4] Lisanby SH. Electroconvulsive therapy for depression. New Engl J Med 2007;357:1939–45. [5] Perera TD, Luber B, Nobler MS. Seizure expression during electro-convulsive therapy: relationships with clinical outcome and cognitive side effects. Neuropsychopharmacol 2004;29:813–25. [6] De Baerdemaeker L, Audenaert K, Peremans K. Anaesthesia for patients with mood disorders. Curr Opin Anaesth 2005;18:333–8. [7] Deiner S, Frost EA. Electroconvulsive therapy and anaesthesia. Int Anesth Clin 2009;47:81–92. [8] Singh PM, Arora S, Borle A, Varma P, Trikha A, Goudra BG. Evaluation of etomidate for seizure duration in electroconvulsivotherapy: a systematic review and metaanalysis. J ECT 2015;31:213–25. [9] MacPherson RD, Loo CK. Cognitive impairment following electroconvulsive therapy — does the choice of anesthetic agent make a difference? J ECT 2008;24:52–6. [10] Bundy BD, Hewer W, Andres FJ, Gass P, Sartorius A. Influence of anesthetic drugs
[32] [33] [34]
[35] [36] [37]
[38]
104
and concurrent psychiatric medication on seizure adequacy during electroconvulsive therapy. J Clin Psychiatry 2010;71:775–7. Sartorius A, Munoz Canales EM, Krumm B. ECT anaesthesia: the lighter the better? Pharmacopsychatry 2006;39:201–4. Boylan LS, Haskett RF, Mulsant BH. Determinants of seizure threshold in ECT: benzodiazepine use, anesthetic dosage, andother factors. J ECT 2000;16:3–18. Andrade C, Thirthalli J, Gangadhar BN. Unilateral non-dominant electrode placement as a risk factor for recall of awareness under anaesthesia during electroconvulsive therapy. J ECT 2007;23:201–3. Sartorius A, Krier A, Andres FJ, Bender HJ, Krumm B, Henn FA. Bi-spectral index monitoring for more effective electroconvulsive therapy? Br J Anaesth 2006;96:806–7. Sackeim HA, Prudic J, Fuller R, Keilp J, Lavori PW, Olfson M. The cognitive effects of electroconvulsive therapy in community settings. Neuropsychopharmacol 2007;32:244–54. Lisanby SH, Maddox JH, Prudic J, Devanand DP, Sackeim HA. The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry 2000;57:581–90. Rosow C, Manberg PJ. Bispectral index monitoring. Anaesthesiology Clinical North America 1998;2:89–107. Stripp T, Jorgensen M, Olsen N. Anaesthesia for electroconvulsive therapy - new tricks for old drugs: a systematic review. Acta Neuropsychiatry 2017(2):1–9. Kayser S, Bewernick BH, Soehle M, Switala C, Gippert SM, Dreimueller N, et al. Degree of postictal suppression depends on seizure induction time in magnetic seizure therapy and electro- convulsive therapy. J ECT 2017;33:167–75. Stroup DF, Berlin JA, Morton SC. Meta-analysis of observational studies in epidemiology: a proposal for reporting. JAMA 2000;283:2008–12. Kranaster L, Hoyer C, Janke C. Bispectral index monitoring and seizure quality optimization in electroconvulsive therapy. Pharmacopsychiatry 2013;46:147–50. Choe Y, Lee S, Lee K, Cheong S, Kim Y, Shin C, et al. Correlation between pre-ictal bispectral index and seizure duration during electroconvulsive therapy under thiopental anaesthesia. Korean J Anesth 2003;45:693–6. White P, Rawal S, Recart A, Thornton L, Litle L, Stool L. Can the bispectral index be used to predict seizure time and awakening after electroconvulsive therapy? Anesth Analg 2003;96:1636–9. Ochiai R, Yamada T, Kiyama S, Nakaoji T, Takeda J. Bispectral index as an indicator of seizure inducibility in electroconvulsive therapy under thiopental anesthesia. Anesth Analg 2004;98:1030–5. Sartorius A, Krier A, Andres F, Bender H, Krumm B, Henn F. Bispectral index monitoring for more effective electroconvulsive therapy? Br J Anaesth 2006;96:806–7. Nishihara F, Saito S. Pre-ictal bispectral index has a positive correlation with seizure duration during electroconvulsive therapy. Anesth Analg 2002;94:1249–52. Gombar S, Aggarwal D, Khanna A, Gombar K, Chavan B. The bispectral electroencephalogram during modified electroconvulsive therapy under propofol anesthesia-relation with seizure duration and awakening. J ECT 2011;27:114–8. Lemmens H, Levi D, Debattista C, Brock-Utne J. The timing of electroconvulsive therapy and bispectral index after anesthesia induction using different drugs does not affect seizure duration. J Clin Anesth 2003;15:29–32. Miyazaki S, Muratani T, Morimoto K, Shimizu S, Tanaka M, Minami T. Relationship between seizure duration and bispectral index during modified electroconvulsive therapy. Masui 2006;55:1222–4. Cai Cai L, Qian X, An J, Yu Z, Wu J, Wen H, et al. Electroconvulsive therapy under general anaesthesia with cisatracurium, laryngeal mask airways, and bispectral index. J ECT 2016;32:17–9. Barr J, Egan TD, Sandoval NF, Zomorodi K, Cohane C, Gambus PL, et al. Propofol dosing regimens for ICU sedation based upon an integrated pharmacokineticpharmacodynamic model. Anesthesiology 2001;95:324–33. Rami-Gonzajez L, Bernardo M, Boget T, Gil-Verona JA, Salamero M, Junque C. Subtypes of memory dysfunction associated with ECT: characteristics and neurobiological bases. J ECT 2001;17:129–35. Kadiyala PK, Kadiyala LD. ECT: a new look at an old friend. Curr Opin Anaesthesiol 2018;31:453–8. Vereecke HE, Vanluchene AL, Mortier EP, Everaert K, Struys MM. The effects of ketamine and rocuronium on the A-line auditory evoked potential index, bispectral index, and spectral entropy monitor during steady state propofol and remifentanil anesthesia. Anesthesiology 2006;105:1122–34. Schuller PJ, Newell S, Strickland PA, Barry JJ. Response of bispectral index to neuromuscular block in awake volunteers. Br J Anaesth 2015;115(Suppl. 1):i95–103. Miner JR, Biros MH, Heegaard W, Plummer D. Bispectral electroencephalographic analysis of patients undergoing procedural sedation in the emergency department. Acad Emerg Med 2003;10:638–43. Zanner R, Pilge S, Kochs EF, Kreuzer M, Schneider G. Time delay of electroencephalogram index calculation: analysis of cerebral state, bispectral, and Narcotrend indices using perioperatively recorded electroencephalographic signals. Br J Anaesth 2009;103:394–9. Thimmaiah R. Effect of a course of electroconvulsive therapy on interictal bispectral index values a prospective study. J ECT 2012;28:20–3.