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BJANE-726; No. of Pages 13 ARTICLE IN PRESS

Rev Bras Anestesiol. 2016;xxx(xx):xxx---xxx

REVISTA
BRASILEIRA DE
ANESTESIOLOGIA Official Publication of the Brazilian Society of Anesthesiology
www.sba.com.br

REVIEW ARTICLE

Benefit of general anesthesia monitored by bispectral

index compared with monitoring guided only by clinical
parameters. Systematic review and meta-analysis
Carlos Rogério Degrandi Oliveira a,b,∗ , Wanderley Marques Bernardo c,d,e ,
Victor Moisés Nunes d

a
Department of Anesthesiology, Hospital Guilherme Alvaro, Santos, SP, Brazil
b
Department of Anesthesiology, Hospital Ana Costa, Santos, SP, Brazil
c
Evidence Based Medicine, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brazil
d
Faculdade de Medicina de Santos, Centro Universitário Lusíada, Santos, SP, Brazil
e
Coordenador do Programa Diretrizes da Associação Médica Brasileira, Santos, SP, Brazil

Received 14 July 2015; accepted 22 September 2015

KEYWORDS Abstract
General anesthesia; Background: The bispectral index parameter is used to guide the titration of general anesthesia;
Anesthetics; however, many studies have shown conflicting results regarding the benefits of bispectral index
Inhalation; monitoring. The objective of this systematic review with meta-analysis is to evaluate the clinical
Intravenous impact of monitoring with the bispectral index parameter.
anesthesia; Methods: The search for evidence in scientific information sources was conducted during
Bispectral December 2013 to January 2015, the following primary databases: Medline/PubMed, LILACS,
index-monitoring Cochrane, CINAHL, Ovid, SCOPUS and TESES. The criteria for inclusion in the study were random-
ized controlled trials, comparing general anesthesia monitored, with bispectral index parameter
with anesthesia guided solely by clinical parameters, and patients aged over 18 years. The crite-
ria for exclusion were studies involving anesthesia or sedation for diagnostic procedures, and
intraoperative wake-up test for surgery of the spine.
Results: The use of monitoring with the bispectral index has shown benefits reducing time to
extubation, orientation in time and place, out of the operating room and post anesthetic care
unit. The risk of nausea and vomiting after surgery was reduced by 12% in patients monitored
with bispectral index. A reduction of 3% in the risk of cognitive impairment postoperatively at
3 months occurred after extubation and 6% reduction in the risk of postoperative delirium in
patients monitored with bispectral index. Furthermore, the risk of intraoperative memory has
been reduced by 1%.

∗ Corresponding author.
E-mail: degrandi@gmail.com (C.R.D. Oliveira).

http://dx.doi.org/10.1016/j.bjane.2015.09.001
0104-0014/© 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights reserved.

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
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BJANE-726; No. of Pages 13 ARTICLE IN PRESS
2 C.R.D. Oliveira et al.

Conclusion: Clinically, monitoring with the BIS can be justified because it allows advantages
in reducing the recovery time after waking, mainly reducing the administration of general
anesthetics and the risk of adverse events.
© 2016 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. All rights
reserved.

PALAVRAS-CHAVE Benefício da anestesia geral com monitoração do índice bispectral em comparação

Anestesia geral; com o monitoramento guiado apenas por parâmetros clínicos. Revisão sistemática e
Anestésicos; meta-análise
Inalação;
Anestesia Resumo
intravenosa; Justificativa: O parâmetro índice bispectral (BIS) é usado para guiar a titulação da anestesia
Monitoração do geral; no entanto, muitos estudos têm mostrado resultados conflitantes quanto aos benefícios
índice bispectral da monitoração do BIS. O objetivo desta revisão sistemática com meta-análise foi avaliar o
impacto clínico da monitoração do parâmetro BIS.
Métodos: A busca por evidências em fontes de informação científicas foi conduzida de dezembro
de 2013 a janeiro de 2015 nas seguintes bases de dados: Medline/PubMed, LILACS, Cochrane,
CINAHL, Ovid, SCOPUS e TESES. Os critérios de inclusão foram estudos randômicos e controlados,
comparando anestesia geral monitorada com o parâmetro BIS com anestesia guiada apenas por
parâmetros clínicos; pacientes com idade superior a 18 anos. Os critérios de exclusão foram
estudos que envolveram anestesia ou sedação para procedimentos de diagnóstico e teste de
despertar no intraoperatório para cirurgia da coluna vertebral.
Resultados: O uso de monitoração com o BIS tem mostrado benefícios como a redução do tempo
de extubação, orientação no tempo e no espaço, alta da sala de cirurgia e da sala de recuperação
pós-anestesia. O risco de náusea e vômito após a cirurgia foi reduzido em 12% em pacientes
monitorados com o BIS. Uma redução de 3% no risco de disfunção cognitiva em três meses de
pós-operatório ocorreu após a extubação e de 6% no risco de delírio pós-operatório em pacientes
monitorados com o BIS. Além disso, o risco de consciência intraoperatória foi reduzido em 1%.
Conclusão: Clinicamente, a monitorização com o BIS pode ser justificada, pois permite
vantagens em reduzir o tempo de recuperação após acordar, principalmente reduzindo a
administração de anestésicos gerais e o risco de eventos adversos.
© 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. Todos os
direitos reservados.

Introduction Methods

Bispectral index (BIS) is a multiprocessor EEG parameter
specially developed to measure the effects of anesthetics
on the brain hypnotic state, making it possible to mea-
sure the depth of anesthesia. The introduction of the BIS
in clinical practice is a reliable method to assess brain
function and allows the titration of hypnotics on cortical
activity.
Due to anesthesia may occur unpredictable responses at
different times of surgery with a great variability among
patients, so the exact dosage of anesthetic to be adminis-
tered still remains a challenge. However, many studies have
shown conflicting results regarding the advantages of BIS
and if this monitoring improves recovery times and hospital
discharges, as well as minimizes adverse events.
The objective of this systematic review with meta-
analysis was to clinically evaluate the objective BIS
monitoring parameter, compared with the clinical param-
eters in general anesthesia.
The research for evidence in scientific sources of informa-
tion was performed by two independent reviewers (WMB,
CRDO) during the period from December 2013 to January
2015, the following primary databases: Medline/PubMed,
LILACS, Cochrane, CINAHL, Ovid, SCOPUS and THESES. The
search strategy was made with the following words: (Anes-
thesia, General OR Anesthetics, Inhalation OR Anesthetics,
Intravenous) AND (Consciousness Monitors OR Monitoring,
Intraoperative OR Bispectral index-monitoring technology
OR Bispectral index-monitoring OR Bispectral index mon-
itoring OR Drug Monitoring OR Awareness OR Monitoring,
Physiologic OR BIS monitoring) AND Random*.
The criteria for inclusion in the study were Randomized
Controlled Trials (RCTs) with level of evidence 1B/2B (Oxford
Centre for Evidence-based Medicine) in English, Spanish or
Portuguese languages, comparing venous or inhaled general
anesthetics monitored with BIS parameter with anesthesia
guided solely by clinical parameters; patients aged over

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
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Benefit of general anesthesia monitored by bispectral index 3

Regarding meta-analysis, the difference was calcu-

Table 1 Considered outcomes.
lated in risk difference for dichotomic variables with
Time for spontaneous eye opening Mantel---Haenszel (M-H) test with 95% Confidence Interval;
Time for eye opening upon verbal command and in mean difference with fixed effect using Inverse Vari-
Time to tracheal extubation ance (IV), with a 95% Confidence Interval, for continuous
Time for orientation in time and place variables.
Time for leaving operating room An I2 of 0% indicates no heterogeneity among studies,
Time for discharge from post anesthesia care unit (PACU) values below 50% indicate a low heterogeneity, and above
Time for hospital discharge 50%, high heterogeneity.
Nausea and vomiting in the postoperative period When the heterogeneity was greater than 50%, a sensitiv-
Cognitive disorders in the postoperative period (1 week ity analysis was performed, removing the studies that were
after extubation) out of the ‘‘forest plot’’. To achieve reduction in hetero-
Cognitive disorders in the postoperative period (3 months geneity remained out of the study meta-analysis.
after extubation)
Postoperative delirium
Intraoperative memory Results

Initially, the search resulted in 1.747 scientific articles. After

18 years. Studies were included with balanced anesthesia
obtained with intravenous anesthetic induction and mainte-
nance inhaled.
The criteria for exclusion were studies involving anesthe-
sia and sedation for diagnostic procedures. Studies involving
intraoperative wake-up test for surgery of the spine were
excluded. Nor were objects of study the clinical trials of
ketamine as venous anesthetic.
This systematic review with meta-analysis was recorded
in PROSPERO database under the number CRD42015017240.
The outcomes considered are described in Table 1.
The results of the meta-analysis were obtained by the
RevMan 5.2 software (Review Manager Computer program.
Version 5.2 Copenhagen: The Nordic Cochrane Centre,
Cochrane Collaboration© 2014).
applying the inclusion and exclusion criteria were selected
17 RCT (Fig. 1).
Table 2 shows the trials selected with the respective lev-
els of evidence, Jadad scale, number of patients randomized
and analyzed, patient numbers in the intervention and con-
trol groups and PICO strategy. A total of 10,761 patients were
analyzed, 5668 in the intervention group and 5093 in the
control group.
Table 3 shows the 36 full-text articles excluded with rea-
sons.
The time for spontaneous eye opening is counted from
the end of the last suture, when then inhaled or intravenous
anesthetic is discontinued. The monitoring with the BIS,
compared exclusively with clinical parameters, showed a
reduction in the time for spontaneous opening 0.62 min
eye (95% CI −1.08, −0.16), with an I2 = 83%. In sensitivity

Records identified through Additional records identified

database searching through other sources
(n=1744) (n=3)

Records screened Records excluded

(n=1747) (n=1694)

Full-text articles assessed Full-text articles excluded,

for eligibility with reasons
(n=53) (n=36)

Studies included in
qualitative synthesis
(n=17)

Studies included in
quantitative synthesis
(meta-analysis)
(n=17)

Figure 1 Consolidated flow diagram (PRISMA Flow Diagram, 2009).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
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BJANE-726; No. of Pages 13 ARTICLE IN PRESS
4 C.R.D. Oliveira et al.

Table 2 Selected randomized clinical trials (RCT).

RCT EL J R/A I/C P I C O
Nelskylä et al. 2B 0 62/62 32/30 ASA 1 or 2, BIS between 50 ‘‘Blinded’’ Time for
(2001)1 between 18 and 50 and 60 years monitor. spontaneous eye
years, Anesthesia was opening,
gynecological adjusted according extubation,
surgery. to clinical orientation in time
parameters. and place, hospital
discharge and
PONV.
Wong et al. 1B 3 68/60 29/31 >60 years, ASA BIS between 50 ‘‘Blinded’’ Time for
(2002)2 1---3, orthopedic and 60. monitor. spontaneous eye
surgery. Anesthesia was opening,
adjusted according orientation in time
to clinical and place and
parameters. PACU discharge.
Luginbühl 2B 2 160/160 80/80 >18 years, BIS between 45 Anesthesia was Time to tracheal
et al. gynecological and 55. adjusted according extubation.
(2003)3 surgery. to clinical
parameters.
Ahmad et al. 1B 3 99/97 49/48 >18 years, BIS between 50 Anesthesia was Time for hospital
(2003)4 gynecological and 60. adjusted according discharge.
surgery. to clinical
parameters.
Başar et al. 2B 0 60/60 30/30 >18 years, ASA 1 or BIS between 40 ‘‘Blinded’’ Time of eye
(2003)5 2, abdominal and 60. monitor. opening upon
surgery. Anesthesia was verbal command.
adjusted according
to clinical
parameters.
Puri and 2B 2 30/30 14/16 >18 years, BIS between 45 ‘‘Blinded’’ Time of eye
Murthy myocardial and 55. monitor. opening upon
(2003)6 revascularization Anesthesia was verbal command,
or valve adjusted according extubation and
replacement with to clinical Intraoperative
cardiopulmonary parameters. memory.
bypass, 18---70
years.
Kreuer et al. 2B 2 120/120 40/40 >18 years, ASA BIS 50 and in the Anesthesia was Time for
(2003)7 1---3, orthopedic last 15 min of 60. adjusted according spontaneous eye
surgery. to clinical opening and
parameters. extubation.
Myles et al. 1B 5 2.503/2.463 1.225/1.238 >18 years with at BIS between 40 Monitor turned off. Time for
(2004)8 least one high risk and 60. Anesthesia was spontaneous eye
factor to adjusted according opening, time for
intraoperative to clinical discharge from
awakening. parameters. PACU and
intraoperative
memory.
Bruhn et al. 2B 2 200/200 71/58 >18 years, ASA BIS of 50. In the Anesthesia was Time for
(2005)9 1---3, between 18 last 15 min BIS of adjusted according spontaneous eye
and 80 years. 60. to clinical opening,
parameters. extubation, nausea
and vomiting in
the post operative
and intraoperative
memory.
Kreuer et al. 1B 4 120/120 40/40 >18 years, ASA I to BIS 50 and in the Anesthesia was Time for
(2005)10 III, orthopedic last 15 min change adjusted according spontaneous eye
surgery. to 60. to clinical opening,
parameters. extubation and
time for leaving
operation room.
Vretzakis et al. 1B 3 130/121 36/44 >18 years, BIS under 60. Anesthesia was Intraoperative
(2005)11 myocardial adjusted according memory.
revascularization to clinical
or valve parameters.
replacement with
cardiopulmonary
bypass, ejection
fraction >45%.

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
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Benefit of general anesthesia monitored by bispectral index 5

Table 2 (Continued)
RCT EL J R/A I/C P I C O
Aimé et al. 2B 1 140/125 34/54 Age between 18 BIS between 40 ‘‘Blinded’’ Time for
(2006)12 and 80 years, ASA and 60. monitor. spontaneous eye
1---3, urologic, Anesthesia was opening and
orthopedic, adjusted according traqueal
abdominal and to clinical extubation.
gynecological parameters.
surgery.
Ibraheim et al. 2B 0 30/30 15/15 >18 years, morbid BIS between 40 Anesthesia was Time of eye
(2008)13 obese, gastric and 60. adjusted according opening upon
band surgery. to clinical verbal command,
parameters extubation and
discharge from
PACU.
Kamal et al. 2B 1 60/57 29/28 >18 years, ASA BIS between 50 ‘‘Blinded’’ Time for
(2009)14 1---3, abdominal and 60. monitor. spontaneous eye
surgery Anesthesia was opening,
adjusted according extubation,
to clinical orientation in time
parameters. and place, leaving
operating room,
discharge from
PACU and
intraoperative
memory.
Zhang et al. 1B 5 5.309/5.228 2.919/2.309 >18 years, total BIS between 40 ‘‘Blinded’’ Intraoperative
(2011)15 intravenous and 60. monitor. memory.
anesthesia Anesthesia was
adjusted according
to clinical
parameters.
Chan et al. 1B 3 921/902 450/452 >60 years, elective BIS between 40 Anesthesia was Time for
(2013)16 non-cardiac and 60. adjusted according spontaneous eye
surgery. to clinical opening discharge
parameters. from PACU,
cognitive
dysfunction in the
postoperative
period (one week
and three months
later) and
delirium.
Radtke et al. 1B 3 1.277/1.155 575/580 >60 years BIS between 40 ‘‘Blinded’’ Cognitive
(2013)17 and 60. monitor. dysfunction in the
Anesthesia was postoperative
adjusted according period (one week
to clinical and three months
parameters. later) and
delirium.
RCT, Randomized Clinical Trial; EL, Evidence Level; J, Jadad score; R/A, patients randomized and analyzed; I/C, intervention
group/control group; P, population; I, intervention; C, control or comparison; O, outcome.

analysis, when removed the study Kreuer et al.14 was
removed we have an I2 = 0%, with reduction of time for
spontaneous eye opening of 0.28 min (95% CI −0.75, 0.20).
However, the statistically significant difference was lost
(Fig. 2).
The time for eye opening upon verbal command is
counted from the end of last suture, when the inhaled or
intravenous anesthetic is discontinued and the patient is
asked to open his eyes. There was a reduction in time to eye
opening at verbal command of 0.63 min (95% CI −1.30, 0.05),
with an I2 = 67%, with no statistically significant difference
(Fig. 3).
The use of BIS reduced 1.18 min in the time of tracheal
extubation (95% CI −1.65, −0.70), with an I2 = 79%. In sensi-
tivity analysis, when the study Kreuer et al.7 was removed,
the time to tracheal extubation reduced 0.87 min (95% CI
−1.36, −0.38), with an I2 = 59%, maintaining, therefore, a
statistically significant difference (Fig. 4).
The combination of three studies1---3 demonstrated that
the time for orientation in time and place reduced 3.08 min
(95% CI −3.70, −2.45) with an I2 = 73%. In sensitivity analy-
sis, when the study Nelskylä et al.1 was removed we have a
reduction of 3.76 min (95% CI −4.55, −2.97) with an I2 = 0%,
maintaining, therefore, a statistically significant difference
(Fig. 5).
When using the BIS, the time for the patient to be able
to get out of the operating room and go to PACU reduced
2.93 min (95% CI −3.68, −2.18), with an I2 = 92%. In sensi-
tivity analysis, when removed the study Kreuer et al.,10 we
have a reduction of 4.89 min (95% CI −5.95, −3.83) with an
I2 = 0%, maintaining, therefore, statistically significant dif-
ference (Fig. 6).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
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Table 3 Full-text articles excluded with reasons.
Article
18
Sebel et al. (1997)
Yli-Hankala et al. (1999)19
Mi et al. (1999)20
Nakayama et al. (2002)21
Lehmann et al. (2002)22
Paventi et al. (2002)23
Lehmann et al. (2003)24
Yamaguchi et al. (2003)25
Buyukkocak et al. (2003)26
Forestier et al. (2003)27
Schneider et al. (2003)28
Schneider et al. (2003)29
Liu (2004)30
Bauer et al. (2004)31
Bestas et al. (2004)32
Boztug et al. (2006)33
Puri et al. (2007)34
Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
ARTICLE IN PRESS
Reason of exclusion
Before incision tetanus stimulation was applied to the ulnar nerve. Any presence of
movement, anesthesia was deepened. In the absence of movement, anesthesia was
maintained. After incision any movement was considered for the deepening of anesthesia.
The study goes out of focus --- BIS intervention compared to the control group (consciousness
guided by clinical parameters only).
The data expression of the outcomes was made in medians.
Patients were monitored with BIS and outcomes were analyzed due to different anesthetic
regimens. The study goes out of focus --- BIS intervention compared to the control group
(consciousness guided by clinical parameters only).
All patients were monitored with BIS and outcomes were analyzed due to different anesthetic
regimens (only propofol or propofol and fentanyl). The study goes out of focus --- BIS
intervention compared to the control group (consciousness guided by clinical parameters
only).
All patients were monitored with BIS and analyzed outcomes resulting from different
anesthetic techniques (with manual propofol infusion vs. propofol in Target Controlled
Infusion --- TCI). The study goes out of focus --- BIS intervention compared to the control group
(consciousness guided by clinical parameters only).
All patients were monitored with BIS and analyzed outcomes resulting from different
anesthetic techniques (manual propofol infusion vs. propofol in TCI). The study goes out of
focus --- BIS intervention compared to the control group (consciousness guided by clinical
parameters only).
All patients were monitored with BIS (group BIS 50 and group BIS 40). The study goes out of
focus --- BIS intervention compared to the control group (consciousness guided by clinical
parameters only).
All patients were monitored with BIS and analyzed outcomes resulting from different
anesthetic drugs and techniques (propofol group/iv induction and sevoflurane group with
inhalational induction in adult by the vital capacity technique). The study goes out of focus ---
BIS intervention compared to the control group (consciousness guided by clinical parameters
only).
All patients were monitored with BIS and outcomes were analyzed due to different anesthetic
drugs, four different methods of sedation associated with topical anesthesia. The study goes
out of focus --- BIS intervention compared to the control group (consciousness guided by
clinical parameters only).
All patients were monitored with BIS and analyzed five groups with different concentrations of
sufentanil. The study goes out of focus --- BIS intervention compared to the control group
(consciousness guided by clinical parameters only).
All patients were monitored with BIS and analyzed four different anesthetic regimens. The
study goes out of focus --- BIS intervention compared to the control group (consciousness
guided by clinical parameters only).
All patients were monitored with BIS and analyzed two different anesthetic regimens. The
study goes out of focus --- BIS intervention compared to the control group (consciousness
guided by clinical parameters only).
Meta-analysis. The criteria for inclusion in the systematic review were randomized controlled
trials.
All patients were monitored with BIS and analyzed two different anesthetic regimens (TCI vs.
manual propofol infusion). The BIS was used but is not described whether it was blinded. The
study goes out of focus --- BIS intervention compared to the control group (consciousness
guided by clinical parameters only).
All 50 patients (two groups of 25) were monitored with BIS and were blinded, with analysis of
two different anesthetic regimes. The study goes out of focus --- BIS intervention compared to
the control group (consciousness guided by clinical parameters only).
Article not found.
All patients were monitored with BIS, with analysis of two different types of propofol infusion.
The study goes out of focus --- BIS intervention compared to the control group (consciousness
guided by clinical parameters only).
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Benefit of general anesthesia monitored by bispectral index 7

Table 3 (Continued)

Article Reason of exclusion

35
Lindholm et al. (2008)
Avidan et al. (2008)36
Bejjani et al. (2009)37
Delfino et al. (2009)38
Kerssens et al. (2009)39
Mashour et al. (2009)40
Satisha et al. (2010)41
Meybohm et al. (2010)42
Leslie et al. (2010)43
Avidan et al. (2009)44
Ellerkmann et al. (2010)45
Yufune et al. (2011)46
Liu et al. (2011)47
Avidan et al. (2011)48
Aimé et al. (2012)49
Mashour et al. (2012)50
Persec et al. (2012)51
Fritz et al. (2013)52
Villafranca et al. (2013)53
The paper analyzes the degree of proficiency in handling the BIS by nurses’ anesthetists. The
study goes out of focus --- BIS intervention compared to the control group (consciousness
guided by clinical parameters only).
In the control group, anesthesia was maintained with BIS ‘‘blinded’’ but with an expired
fraction of 0.7---1.3 minimum alveolar concentration of inhaled anesthetic.
All patients were monitored with BIS with memory processing analysis. The study goes out of
focus --- BIS intervention compared to the control group (consciousness guided by clinical
parameters only).
All patients were monitored with BIS or cerebral state index, with analysis of propofol infusion
with these two types of monitoring. The study goes out of focus --- BIS intervention compared
to the control group (consciousness guided by clinical parameters only).
Study of intraoperative memory and retrieval of words heard during the trans-operative,
through memory tests postoperatively.
Cohort study. The criteria for inclusion in the systematic review were randomized controlled
trials.
Cohort study. The criteria for inclusion in the systematic review were randomized controlled
trials.
Protocol study. The criteria for inclusion in the systematic review were randomized controlled
trials.
Retrospective cohort study. The criteria for inclusion in the systematic review were
randomized controlled trials.
Protocol study. The criteria for inclusion in the systematic review were randomized controlled
trials.
Inhalation or intravenous anesthesia, complemented by regional anesthesia (combined
anesthesia). The study goes out of focus --- BIS intervention compared to the control group
(consciousness guided by clinical parameters only).
The 38 patients were monitored with BIS and outcomes were analyzed due to different
anesthetic regimens, as well as different concentrations of remifentanil. The study goes out
of focus --- BIS intervention compared to the control group (consciousness guided by clinical
parameters only).
All patients were monitored with BIS and outcomes were analyzed due to different anesthetic
regimens, target controlled infusion of propofol vs. closed-loop management. The study goes
out of focus --- BIS intervention compared to the control group (consciousness guided by
clinical parameters only).
The control group was adjusted for maintaining an expired fraction of 0.7---1.3 minimum
alveolar concentration of inhaled anesthetic.
The 102 patients were monitored with BIS or Entropy, in both groups, the values were blinded,
and anesthesia was conducted by clinical parameters. The study goes out of focus --- BIS
intervention compared to the control group (consciousness guided by clinical parameters
only).
The control group was blinded, but adjusted to a minimum alveolar concentration of inhaled
anesthetic by age.
The results of this study cannot be meta-analyzed as they provide no standard deviation.
Retrospective cohort study. The criteria for inclusion in the systematic review were
randomized controlled trials.
Retrospective cohort study. The criteria for inclusion in the systematic review were
randomized controlled trials.

The time for patients to achieve the discharge criteria
in the PACU (Aldrete-Kroulik modified index) was reduced
4.05 min (95% CI −7.23, −0.87), with I2 = 91%. In sensitiv-
ity analysis, when removed the study Ibraheim et al.,13
we have a reduction of 22.35 min (95% CI −31.01, −13.69)
with I2 = 20%, maintaining statistically significant difference
(Fig. 7).
There was no statistically significant difference between
the intervention and control in the evaluation of the neces-
sary time to hospital discharge (95% CI, −22.08, 30.52) with
I2 = 0% (Fig. 8).
The incidence of PONV was lower in anesthesia conducted
with BIS, with a risk reduction of 12% (95% CI −0.22, −0.01)
with I2 = 61%, which was statistically significant (Fig. 9).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
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BJANE-726; No. of Pages 13 ARTICLE IN PRESS
8 C.R.D. Oliveira et al.

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 5 5 32 5 2 30 6.1% 0.00 [–1.87, 1.87] 2001
Wong J 2002 4 2.1 29 4.9 3.4 31 10.6% –0.90 [–2.32, 0.52] 2002
Kreuer S 2003 3.5 2.9 40 9.3 5.2 40 6.3% –5.80 [–7.65, –3.95] 2003
Bruhn J 2005 5.9 3.4 71 5.6 2.5 58 20.5% 0.30 [–0.72, 1.32] 2005
Kreuer S 2005 4.2 2.1 40 4.7 2.2 40 24.0% –0.50 [–1.44, 0.44] 2005
Aimé I 2006 7.6 4.1 34 8 3.9 54 7.1% –0.40 [–2.13, 1.33] 2006
Kamal NM 2009 4.1 1.6 29 4.4 1.9 28 25.5% –0.30 [–1.21, 0.61] 2009

Total (95% CI) 275 281 100.0% –0.62 [–1.08, –0.16]

Heterogeneity: Chi2=34.57, df=6 (P<.00001); I2=83%
–10 –5 0 5 10
Test for overall effect: Z=2.64 (P=.008)
BIS Control
BIS Control Mean difference Mean difference
Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 5 5 32 5 2 30 6.5% 0.00 [–1.87, 1.87] 2001
Wong J 2002 4 2.1 29 4.9 3.4 31 11.3% –0.90 [–2.32, 0.52] 2002
Kreuer S 2003 3.5 2.9 40 9.3 5.2 40 0.0% –5.80 [–7.65, –3.95] 2003
Bruhn J 2005 5.9 3.4 71 5.6 2.5 58 21.9% 0.30 [–0.72, 1.32] 2005
Kreuer S 2005 4.2 2.1 40 4.7 2.2 40 25.6% –0.50 [–1.44, 0.44] 2005
Aimé I 2006 7.6 4.1 34 8 3.9 54 7.6% –0.40 [–2.13, 1.33] 2006
Kamal NM 2009 4.1 1.6 29 4.4 1.9 28 27.2% –0.30 [–1.21, 0.61] 2009

Total (95% CI) 235 241 100.0% –0.28 [–0.75, 0.20]

Heterogeneity: Chi2=2.29, df=5 (P=.81); I2 = 0%
–10 –5 0 5 10
Test for overall effect: Z=1.13 (P=.26)
BIS Control

Figure 2 Time for spontaneous eye opening (min).

There was no risk reduction of cognitive disorders in the Discussion

post operatory with 1 week after extubation, in patients
using BIS (95% CI, −0.06, 0.01, I2 = 0%). There was no statis-
tically significant difference between the intervention and
control (Fig. 10).
The cognitive disorders after surgery at 3 months after
extubation had a risk reduction of 3% (95% CI −0.05, −0.00),
and I2 = 52%, which was statistically significant (Fig. 11).
There was a 6% reduction in the risk of delirium in
the post operatory in patients monitored with BIS (95% CI
−0.10, −0.03) I2 = 11%, which was statistically significant
(Fig. 12).
The use of BIS had a risk reduction of 1% for the intraoper-
ative memory (Recall), a statistically significant difference
(−0.01 [95% CI, −0.01, −0.00]) with I2 = 0%. The intraoper-
ative memory is the awakening confirmed by the patient.
It was not made a differentiation of studies with patients
classified as low or high risk for intraoperative memory
(Fig. 13).
The use of monitoring with the BIS showed benefits by
reducing the time to extubation in 0.87 min, orientation in
time and place in 3.76 min and leaving operating room in
4.89 min. Patients had a reduction in 22.35 min to reach the
criteria for PACU discharge. The combined results of the
studies showed that the incidence of PONV risk reduction
of 12% in patients BIS monitoring.
Cognitive disorders in postoperative patients with 1 week
after extubation did not show statistically significant dif-
ference. However, there was a 3% reduction in the risk of
cognitive disorders in the postoperative patients 3 months
after extubation. There was a 6% reduction in the risk of
delirium incidence of postoperative in patients using BIS
monitoring. In addition, the memory of the intraoperative
risk had a reduction of 1% after using BIS.
The 17 studies selected by the pre-established crite-
ria showed a heterogeneity that was soon noticed. Factors

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Basar H 2003 8.25 1.8 30 8.59 1 30 83.6% –0.34 [–1.08, 0.40] 2003
Puri GD 2003 18.5 11.5 14 28 15 16 0.5% –9.50 [–19.00, 0.00] 2003
Ibraheim O 2008 6.8 2.1 15 8.66 2.6 15 15.9% –1.86 [–3.55, 0.17] 2008

Total (95% CI) 59 61 100.0% –0.63 [–1.30, 0.05]

Heterogeneity: Chi2=5.97, df=2 (P=.05); I2=67%
–10 –5 0 5 10
Test for overall effect: Z=1.82 (P=.07)
BIS Control

Figure 3 Time for eye opening upon verbal command (min).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
+Model
BJANE-726; No. of Pages 13 ARTICLE IN PRESS
Benefit of general anesthesia monitored by bispectral index 9

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 2 2 32 3 2 30 23.0% –1.00 [–2.00, –0.00] 2001
Luginbũl M, 2003 (a) 6.8 4.6 40 10.5 5.9 40 4.2% –3.70 [–6.02, –138] 2003
Luginbũl M, 2003 (b) 6.5 4.1 40 8.3 6.1 40 4.4% –1.80 [–4.08, 0.48] 2003
Puri GD 2003 7.2 4.3 14 6 3.2 16 3.0% 1.20 [–1.54, 3.94] 2003
Kreuer S 2003 4.1 2.9 40 9.7 5.3 40 6.5% –5.60 [ –7.47, –3.73] 2003
Kreuer S 2005 4.4 2.2 40 5.4 4.4 40 9.8% –1.00 [–2.52, 0.52] 2005
Bruhn J 2005 6.6 3.5 71 6.3 2.4 58 21.8% 0.30 [–0.72, 1.32] 2005
Aimé I 2006 11.1 5.1 34 14.2 9 54 2.6% –3.10 [–6.05, –0.15] 2006
Ibraheim O 2008 9.26 2 15 11.8 2.9 15 7.2% –2.54 [–4.32, –0.76] 2008
Kamal NM 2009 4.3 2.1 29 4.8 2.3 28 17.4% –0.50 [–1.64, 0.64] 2009

Total (95% CI) 355 361 100.0% –1.18 [–1.65, –0.70]

2
Heterogeneity: Chi2=42.58, df=9 (P<.00001); I =79%
–10 –5 0 5 10
Test for overall effect: Z=4.83 (P<.00001)
BIS Control

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 2 2 32 3 2 30 24.6% –1.00 [–2.00, –0.00] 2001
Luginbũl M, 2003 (a) 6.8 4.6 40 10.5 5.9 40 4.5% –3.70 [–6.02, –138] 2003
Luginbũl M, 2003 (b) 6.5 4.1 40 8.3 6.1 40 4.7% –1.80 [–4.08, 0.48] 2003
Puri GD 2003 7.2 4.3 14 6 3.2 16 3.2% 1.20 [–1.54, 3.94] 2003
Kreuer S 2003 4.1 2.9 40 9.7 5.3 40 0.0% –5.60 [ –7.47, –3.73] 2003
Kreuer S 2005 4.4 2.2 40 5.4 4.4 40 10.5% –1.00 [–2.52, 0.52] 2005
Bruhn J 2005 6.6 3.5 71 6.3 2.4 58 23.4% 0.30 [–0.72, 1.32] 2005
Aimé I 2006 11.1 5.1 34 14.2 9 54 2.8% –3.10 [–6.05, –0.15] 2006
Ibraheim O 2008 9.26 2 15 11.8 2.9 15 7.7% –2.54 [–4.32, –0.76] 2008
Kamal NM 2009 4.3 2.1 29 4.8 2.3 28 18.6% –0.50 [–1.64, 0.64] 2009

Total (95% CI) 315 321 100.0% –0.87 [–1.36, –0.38]

Heterogeneity: Chi2=19.65, df=8 (P=.01); I2=59%
Test for overall effect: Z=3.45 (P=.0006) –10 –5 0 5 10
BIS Control

Figure 4 Time to tracheal extubation (min). (a) Time to tracheal extubation with propofol. (b) Time to tracheal extubation with
desflurane.

related to anesthetic technique, the patient and the sur-
gical procedure were observed. Studies that analyzed the
consumption of anesthetics showed no standardized meas-
ures that enabled the selection of at least two studies for
the meta-analysis.
The study Ibraheim et al.13 involved morbidly obese
patients. Three studies were conducted exclusively with
patients over 60 years of age.2,16,17
Puri et al.6 and Vretzakis et al.11 studied patients under-
going cardiac surgery with extracorporeal circulation.

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 6 2 32 3 2 30 38.8% –2.00 [–3.00, –1.00] 2001
Wong J 2002 9.5 3.1 29 13.1 3.8 31 12.6% –3.60 [–5.35, –1.85] 2002
Kamal NM 2009 7.4 1.5 29 11.2 1.9 28 48.6% –3.80 [–4.69, –2.91] 2009

Total (95% CI) 90 89 100.0% –3.08 [–3.70, –2.45]

Heterogeneity: Chi2=7.36, df=2 (P=.03); I2=73%
–10 –5 0 5 10
Test for overall effect: Z=9.71 (P<.00001)
BIS Control

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 2 2 32 3 2 30 0.0% –2.00 [–3.00, –1.00] 2001
Wong J 2002 9.5 3.1 29 13.1 3.8 31 20.6% –3.60 [–5.35, –1.85] 2002
Kamal NM 2009 7.4 1.5 29 11.2 1.9 28 79.4% –3.80 [–4.69, –2.91] 2009

Total (95% CI) 58 59 100.0% –3.76 [–4.55, –2.97]

Heterogeneity: Chi2=.04, df=1 (P=.84); I2=0%
–10 –5 0 5 10
Test for overall effect: Z= 9.28 (P<.00001)
BIS Control

Figure 5 Time for orientation in time and place (min).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
+Model
BJANE-726; No. of Pages 13 ARTICLE IN PRESS
10 C.R.D. Oliveira et al.

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Kreuer S 2003 7 3.2 40 12.4 5.7 40 13.6% –5.40 [–7.43, –3.37] 2003
Kreuer S 2005 8.4 2.4 40 9.4 2.4 40 50.5% –1.00 [–2.05, 0.05] 2005
Kamal NM 2009 9.4 1.9 29 14.1 2.8 28 35.9% –4.70 [–5.95, –3.45] 2009

Total (95% CI) 109 108 100.0% –2.93 [–3.68, –2.18]

Heterogeneity: Chi2=26.39, df=2 (P<.00001); I2=92%
–10 –5 0 5 10
Test for overall effect: Z=7.68 (P<.00001)
BIS Control

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Kreuer S 2003 7 3.2 40 12.4 5.7 40 27.5% –5.40 [–7.43, –3.37] 2003
Kreuer S 2005 8.4 2.4 40 9.4 2.4 40 0.0% –1.00 [–2.05, 0.05] 2005
Kamal NM 2009 9.4 1.9 29 14.1 2.8 28 72.5% –4.70 [–5.95, –3.45] 2009

Total (95% CI) 69 68 100.0% –4.89 [–5.95, –3.83]

Heterogeneity: Chi2=.33, df=1 (P<.56); I2=0%
–10 –5 0 5 10
Test for overall effect: Z=9.03 (P<.00001)
BIS Control

Figure 6 Time for leaving operation room (min).

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Wong J 2002 111 30 29 123 48 31 2.5% –12.00 [–32.12, 8.12] 2002
Ibraheim O 2008 29.8 4.74 15 31 4.81 15 86.5% –1.20 [–4.62, 2.22] 2008
Kamal NM 2009 53.9 14.7 29 78.6 21.5 28 11.0% –24.70 [–34.29, –15.11] 2009

Total (95% CI) 73 74 100.0% –4.05 [–7.23, –0.87]

Heterogeneity: Chi2=21.07, df=2 ( P<.0001); I2=91%
–100 –50 0 50 100
Test for overall effect: Z=2.50 (P=.01)
BIS Control

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Wong J 2002 111 30 29 123 48 31 18.5% –12.00 [–32.12, 8.12] 2002
Ibraheim O 2008 29.8 4.74 15 31 4.81 15 0.0% –1.20 [–4.62, 2.22] 2008
Kamal NM 2009 53.9 14.7 29 78.6 21.5 28 81.5% –24.70 [–34.29, –15.11] 2009

Total (95% CI) 58 59 100.0% –22.35 [–31.01, –13.69]

Heterogeneity: Chi2=1.25, df=1 ( P=.26); I2=20%
–100 –50 0 50 100
Test for overall effect: Z=5.06 (P<.00001)
BIS Control

Figure 7 Time for discharge from PACU (min).

Myles et al.8 studied patients with at least one high-risk
factor for awakening with intraoperative memories (high
risk heart surgery, cesarean sections, hypovolemic shock,
rigid bronchoscopy, cardiovascular instability and expected
hypotension during surgery, lung disease in advanced stages,
historical of awakening with intraoperative memories, dif-
ficult airway, high consumption of alcohol, chronic use
of benzodiazepines or opioids and therapy with protease
inhibitors).
The outcomes analyzed with continuously variable
related to the time of recovery and discharge of patients
were: time for spontaneous eye opening, time for eye open-
ing upon verbal command, time for extubation, time for
orientation in time and place, time for leaving operating

BIS Control Mean difference Mean difference

Study or Subgroup Mean SD Total Mean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI
Nelskylã KA 2001 306 85 32 298 124 30 24.4% 8.00 [–45.26, 61.26] 2001
Ahmad S 2003 203 78 49 200 74 48 75.6% 3.00 [–27.25, 33.25] 2003

Total (95% CI) 81 78 100.0% 4.22 [–22.08, 30.52]

Heterogeneity: Chi2=0.03, df=1 (P=.87); I2=0%
–100 –50 0 50 100
Test for overall effect: Z=0.31 (P=.75)
BIS Control

Figure 8 Time to hospital discharge (min).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
+Model
BJANE-726; No. of Pages 13 ARTICLE IN PRESS
Benefit of general anesthesia monitored by bispectral index 11

BIS Control Risk difference Risk difference

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI Year M-H, Fixed, 95% CI
Nelskylã KA 2001 5 32 12 30 32.7% –0.24 [–0.46, –0.03] 2001
Bruhn J 2005 6 71 8 58 67.3% –0.05 [–0.16, 0.06] 2005

Total (95% CI) 103 88 100.0% –0.12 [–0.22, –0.01]

Total events 11 20
Heterogeneity: Chi2=2.59, df=1 (P=.11); I2=61%
–1 –0.5 0 0.5 1
Test for overall effect: Z=2.22 (P=.03)
BIS Control

Figure 9 Postoperative nausea and vomiting (PONV) --- n (%).

BIS Control Risk difference Risk difference

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
Chan 2013 98 450 104 452 43.9% –0.01 [–0.07, 0.04]
Radtke 2013 70 575 90 580 56.1% –0.03 [–0.07, 0.01]

Total (95% CI) 1025 1032 100.0% –0.12 [–0.06, –0.01]

Total events 168 194
Heterogeneity: Chi2=.39, df=1 (P=.53); I2=0%
–1 –0.5 0 0.5 1
Test for overall effect: Z=1.45 (P=.15)
BIS Control

Figure 10 Cognitive disorders in the postoperative period (1 week after extubation) --- n (%).

BIS Control Risk difference Risk difference

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI
Chan 2013 46 450 66 452 43.9% –0.04 [–0.09, –0.00]
Radtke 2013 21 575 28 580 56.1% –0.01 [–0.03, 0.01]

Total (95% CI) 1025 1032 100.0% –0.03 [–0.05, –0.00]

Total events 67 94
2 2
Heterogeneity: Chi =2.08, df=1 (P=.15); I =52%
–0.5 –0.25 0 0.25 0.5
Test for overall effect: Z=2.21 (P=.03)
BIS Control

Figure 11 Cognitive disorders in the postoperative period (3 months after extubation) --- n (%).

BIS Control Risk difference Risk difference

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI Year M-H, Fixed, 95% CI
Chan 2013 70 450 109 452 43.9% –0.09 [–0.14, –0.03] 2013
Radtke 2013 95 575 28 580 56.1% –0.05 [–0.09, –0.00] 2013

Total (95% CI) 1025 1032 100.0% –0.06 [–0.10, –0.03]

Total events 165 233
2 2
Heterogeneity: Chi =1.12, df =1 (P=.29); I =11%
–1 –0.5 0 0.5 1
Test for overall effect: Z=3.74 (P=.0002)
BIS Control

Figure 12 Postoperative delirium --- n (%).

BIS Control Risk difference Risk difference

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI Year M-H, Fixed, 95% CI
Puri GD 2003 0 14 1 16 0.4% –0.06 [–0.23, 0.10] 2003
Myles PS 2004 2 1225 11 1238 31.4% –0.01 [–0.01, –0.00] 2004
Bruhn J 2005 0 71 0 58 1.6% 0.00 [–0.03, 0.03] 2005
Kamal NM 2009 0 29 0 28 0.7% 0.00 [–0.07, 0.07] 2009
Zhang C 2011 4 2919 15 2309 65.8% –0.01 [–0.01, –0.00] 2011

Total (95% CI) 4258 3649 100.0% –0.01 [–0.01, –0.00]

Total events 6 27
2 2
Heterogeneity: Chi =1.04, df=4 (P=.90); I =0%
–0.1 –0.05 0 0.05 0.1
Test for overall effect: Z=3.73 (P=.0002)
BIS Control

Figure 13 Intraoperative memory --- n (%).

Please cite this article in press as: Oliveira CRD, et al. Benefit of general anesthesia monitored by bispectral index
compared with monitoring guided only by clinical parameters. Systematic review and meta-analysis. Rev Bras Anestesiol.
2016. http://dx.doi.org/10.1016/j.bjane.2015.09.001
+Model
BJANE-726; No. of Pages 13 ARTICLE IN PRESS
12
room, time for PACU discharge and time for hospital dis-
charge.
The outcomes of dichotomous variable, related to
adverse events were PONV, cognitive disorders in the post-
operative 1 week after extubation, cognitive disorders in
the postoperative 3 months after extubation, postoperative
delirium and intraoperative memory.
Some primary studies contributed only one outcome
analyzed.3---5,11,15
The individualization of outcomes derived from studies
involving balanced anesthesia or total intravenous anesthe-
sia was not made.
Clinically, the cost of implementation of BIS monitoring
can be justified by allowing advantages in the maintenance
of ambulatory surgeries as well as in the techniques of early
awakening and especially it can reduce the incidence of
adverse events.
The cost of the disposable electrode is a cause of dis-
cussion about the value in use of BIS. Thus, it is important
the active participation of professionals, primarily with
health administrators, in developing a policy plan that opti-
mize resources and give greater safety and comfort for the
patients.
So far, there is no gold standard to span the entire spec-
trum of anesthetic effect on the central nervous system, and
the BIS is undoubtedly the most studied, but is one of many
monitors derived from EEG used nowadays. Monitoring the
depth of anesthesia as new technology is in its beginning.
The new boundary is the individualization of monitoring the
hypnotic and its effects on the central nervous system.
Conflicts of interest
The authors declare no conflicts of interest.
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