Rev. Bras. Anestesiol. vol.67 número1

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REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologia

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_Hospital_Guilherme_Alvaro,_Departamento_de_{Anestesiologia,}_Santos,_SP,_Brazil

b_Hospital_Ana_Costa,_Departamento_de_{Anestesiologia,}_Santos,_SP,_Brazil

c_Universidade_de_São_Paulo,_Faculdade_de_Medicina,_Medicina_Baseada_em_Evidência,_São_Paulo,_SP,_Brazil

d_Centro_{Universitário}_Lusíada,_Faculdade_de_Medicina_de_Santos,_Santos,_SP,_Brazil

e_Programa_Diretrizes_da_{Associac¸ão}_Médica_Brasileira,_Santos,_SP,_Brazil

Received14July2015;accepted22September2015 Availableonline14April2016

KEYWORDS Generalanesthesia; Anesthetics; Inhalation; Intravenous anesthesia; Bispectral index-monitoring

Abstract

Background: Thebispectralindexparameterisusedtoguidethetitrationofgeneralanesthesia; however,manystudieshaveshownconflictingresultsregardingthebenefitsofbispectralindex monitoring.Theobjectiveofthissystematicreviewwithmeta-analysisistoevaluatetheclinical impactofmonitoringwiththebispectralindexparameter.

Methods:The search for evidence in scientific information sources was conducted during December2013toJanuary 2015,thefollowing primarydatabases:Medline/PubMed,LILACS, Cochrane,CINAHL,Ovid,SCOPUSandTESES.Thecriteriaforinclusioninthestudywere random-izedcontrolledtrials,comparinggeneralanesthesiamonitored,withbispectralindexparameter withanesthesiaguidedsolelybyclinicalparameters,andpatientsagedover18years.The crite-riaforexclusionwerestudiesinvolvinganesthesiaorsedationfordiagnosticprocedures,and intraoperativewake-uptestforsurgeryofthespine.

Results:The use ofmonitoringwith thebispectralindex hasshown benefits reducing time to extubation,orientation in timeand place, anddischarge from boththe operating room andpostanestheticcareunit.Theriskofnauseaandvomitingaftersurgerywasreducedby 12% inpatients monitoredwith bispectralindex.Occurred areductionof3% inthe riskof cognitiveimpairmentpostoperativelyat3monthspostoperativelyand6%reductionintherisk ofpostoperativedeliriuminpatientsmonitoredwithbispectralindex.Furthermore,theriskof intraoperativememoryhasbeenreducedby1%.

∗_{Corresponding}_author.

E-mail:[email protected](C.R.Oliveira). http://dx.doi.org/10.1016/j.bjane.2015.09.001

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Conclusion: Clinically,anesthesiamonitoringwith theBIScanbe justifiedbecauseitallows advantagesfromreducingtherecoverytimeafterwaking,mainlybyreducingtheadministration ofgeneralanestheticsaswellastheriskofadverseevents.

PALAVRAS-CHAVE Anestesiageral; Anestésicos; Inalac¸ão; Anestesia intravenosa; Monitorac¸ãodo índicebispectral

Benefíciodaanestesiageralcommonitorac¸ãodoíndicebispectralemcomparac¸ão comomonitoramentoguiadoapenasporparâmetrosclínicos.Revisãosistemáticae metanálise

Resumo

Justificativa: Oparâmetroíndicebispectral(BIS)éusadoparaguiaratitulaçãodaanestesia geral;noentanto,muitosestudostêmmostradoresultadosconflitantesquantoaosbenefícios damonitoraçãodoBIS. Oobjetivodestarevisão sistemáticacommeta-análisefoi avaliaro impactoclínicodamonitoraçãodoparâmetroBIS.

Métodos: Abuscaporevidênciasemfontesdeinformac¸ãocientíficasfoiconduzidadedezembro de2013ajaneirode2015nasseguintesbasesdedados:Medline/PubMed,LILACS,Cochrane, CINAHL,Ovid,SCOPUSeTESES.Oscritériosdeinclusãoforamestudosrandomizadose controla-dos,comparandoanestesiageralmonitoradacomoparâmetroBIScomanestesiaguiadaapenas porparâmetrosclínicosempacientescomidadesuperiora18anos.Oscritériosdeexclusão foramestudosqueenvolveramanestesiaousedac¸ãoparaprocedimentosdediagnósticoeteste dedespertarnointraoperatóriodecirurgiadacolunavertebral.

Resultados: OusodemonitoraçãocomoBISmostroubenefícioscomoareduçãodotempode extubação,orientaçãonotempoenoespaço,altadasaladecirurgiaedasaladerecuperação pós-anestesia.Oriscodenáuseasevômitosnopós-operatóriofoireduzidoem12%empacientes monitorados comoBIS.Ocorreuumareduçãode3%noriscodedisfunçãocognitivaemtrês mesesdopós-operatórioe6%noriscodedelíriopós-operatórioempacientesmonitoradoscom oBIS.Alémdisso,oriscodedespertarcommemóriaintraoperatóriafoireduzidoem1%. Conclusão:Clinicamente, amonitorizaçãocomoBISpodeserjustificada,poispermite van-tagens em reduzir o tempo de recuperação, principalmente reduzindo a administração de anestésicosgeraiseoriscodeeventosadversos.

Introduction

Bispectral index (BIS) is a multiprocessor EEG parameter

specially developedtomeasure theeffects ofanesthetics

on the brain hypnotic state, making it possible to

mea-sure the depthof anesthesia. The introduction of the BIS

in clinical practice is a reliable method to assess brain

function and allows the titrationof hypnotics on cortical activity.

Duetoanesthesiamayoccurunpredictableresponsesat

different times of surgery with a great variability among

patients,sotheexactdosageof anesthetictobe adminis-teredstillremainsachallenge.However,manystudieshave

shown conflicting results regarding the advantages of BIS

andifthismonitoringimprovesrecoverytimesandhospital discharges,aswellasminimizesadverseevents.

The objective of this systematic review with

meta-analysis was to clinically evaluate the objective BIS

monitoring parameter, comparedwith the clinical

param-etersingeneralanesthesia.

Methods

The research for evidence in scientific sources of

infor-mation was performed by two independent reviewers

(CRDO, WMB) during the period from December 2013

to January 2015, the following primary databases:

Med-line/PubMed, LILACS, Cochrane, CINAHL, Ovid, SCOPUS

and THESES. The search strategy was made with the

following words: (Anesthesia, General OR Anesthetics,

InhalationORAnesthetics,Intravenous)AND(Consciousness MonitorsORMonitoring,IntraoperativeORBispectral

index-monitoring technology OR Bispectral index-monitoring OR

BispectralindexmonitoringORDrugMonitoringOR

Aware-ness OR Monitoring, Physiologic OR BIS monitoring) AND

Random*.

ThecriteriaforinclusioninthestudywereRandomized

ControlledTrials(RCTs)withlevelofevidence1B/2B(Oxford CentreforEvidence-basedMedicine)inEnglish,Spanishor

Portugueselanguages,comparingvenousorinhaledgeneral

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Table1 Consideredoutcomes. Timeforspontaneouseyeopening

Timeforeyeopeninguponverbalcommand Timetotrachealextubation

Timefororientationintimeandplace Timeforleavingoperatingroom

Timefordischargefrompostanesthesiacareunit(PACU) Timeforhospitaldischarge

Postoperativenauseaandvomiting(PONV) Cognitivedisordersinthepostoperativeperiod (1weekafterextubation)

Cognitivedisordersinthepostoperativeperiod (3monthsafterextubation)

Postoperativedelirium Intraoperativememory

guidedsolelybyclinicalparameters;patientsagedover18 years.

Thecriteriaforexclusionwerestudiesinvolving anesthe-siaandsedationfordiagnosticprocedures.Studiesinvolving intraoperativewake-up testfor surgery ofthe spinewere excluded. Nor were objects of study the clinical trials of ketamineasvenousanesthetic.

Thissystematicreviewwithmeta-analysiswasrecorded inPROSPEROdatabaseunderthenumberCRD42015017240.

TheoutcomesconsideredaredescribedinTable1.

The results of the meta-analysiswere obtainedby the

RevMan5.2software(Review ManagerComputerprogram.

Version 5.2 Copenhagen: The Nordic Cochrane Centre,

CochraneCollaboration©_2014).

Regarding meta-analysis, the difference was

calcu-lated in risk difference for dichotomic variables with

Mantel---Haenszel (M-H) test with95%ConfidenceInterval; andinmeandifferencewithfixedeffectusingInverse

Vari-ance (IV), witha 95% Confidence Interval,for continuous

variables.

An I2 _of _0% _indicates _no _{heterogeneity} _among _studies,

valuesbelow50%indicatealowheterogeneity,andabove

50%,highheterogeneity.

Whentheheterogeneitywasgreaterthan50%,a sensitiv-ityanalysiswasperformed,removingthestudiesthatwere out ofthe ‘‘forestplot’’. To achievereductionin

hetero-geneityremainedoutofthestudymeta-analysis.

Results

Initially,thesearchresultedin1.747scientificarticles.After applyingtheinclusionandexclusioncriteriawereselected 17RCT(Fig.1).

Table2showsthetrialsselectedwiththerespective

lev-elsofevidence,Jadadscale,numberofpatientsrandomized andanalyzed,patientnumbersintheinterventionand con-trolgroupsandPICOstrategy.Atotalof10,761patientswere

analyzed, 5668 in the intervention groupand 5093 in the

controlgroup.

Table3showsthe36full-textarticlesexcludedwith

rea-sons.

Thetimefor spontaneouseye openingis countedfrom

theendofthelastsuture,whentheninhaledorintravenous

anesthetic is discontinued. The monitoring with the BIS,

compared exclusively with clinical parameters, showed a

reduction in the time for spontaneous opening 0.62min

eye (95% CI−1.08, −0.16), withan I2=83%.In sensitivity

analysis, when removed the study Kreuer et al.7 _was

removed we have an I2₌_0%, _with _reduction _of _time _for

Records identified through database searching

(n=1744)

Additional records identified through other sources

(n=3)

Records excluded (n=1694) Records screened

(n=1747)

Full-text articles assessed for eligibility

(n=53)

Full-text articles excluded, with reasons

(n=36)

Studies included in qualitative synthesis

(n=17)

Studies included in quantitative synthesis

(meta-analysis) (n=17)

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Table2 Selectedrandomizedclinicaltrials(RCT).

RCT EL J R/A I/C P I C O

Nelskyläetal. (2001)1

2B 0 62/62 32/30 ASAIorII,

between18and50 years,

gynecological surgery.

BISbetween50 and60years

‘‘Blinded’’ monitor. Anesthesiawas adjustedaccording toclinical parameters. Timefor spontaneouseye opening, extubation, orientationintime andplace,hospital dischargeand PONV. Wongetal.

(2002)2

1B 3 68/60 29/31 >60years,ASA

I---III,orthopedic surgery.

BISbetween50 and60. ‘‘Blinded’’ monitor. Anesthesiawas adjustedaccording toclinical parameters. Timefor spontaneouseye opening, orientationintime andplaceand PACUdischarge. Luginbühl

etal. (2003)3

2B 2 160/160 80/80 >18years,

BISbetween45 and55.

Anesthesiawas adjustedaccording toclinical parameters.

Timetotracheal extubation.

Ahmadetal. (2003)4

1B 3 99/97 49/48 >18years,

BISbetween50 and60.

Timeforhospital discharge.

Bas¸aretal. (2003)5

2B 0 60/60 30/30 >18years,ASAIor II,abdominal surgery.

BISbetween40 and60. ‘‘Blinded’’ monitor. Anesthesiawas adjustedaccording toclinical parameters.

Timeofeye openingupon verbalcommand.

Puriand Murthy (2003)6

2B 2 30/30 14/16 >18years,

myocardial revascularization orvalve replacementwith cardiopulmonary bypass,18---70 years.

BISbetween45 and55. ‘‘Blinded’’ monitor. Anesthesiawas adjustedaccording toclinical parameters.

Timeofeye openingupon verbalcommand andextubation, intraoperative memory.

Kreueretal. (2003)7

2B 2 120/120 40/40 >18years,ASA I-III,orthopedic surgery.

BIS50andinthe last15minof60.

Anesthesiawas adjustedaccording toclinical parameters. Timefor spontaneouseye openingand extubation. Mylesetal.

(2004)8

1B 5 2.503/2.463 1.225/1.238 >18yearswithat leastonehighrisk factorto intraoperative awakening.

BISbetween40 and60.

Monitorturnedoff. Anesthesiawas adjustedaccording toclinical parameters. Timefor spontaneouseye opening,timefor dischargefrom PACUand intraoperative memory. Bruhnetal.

(2005)9

2B 2 200/200 71/58 >18years,ASA I-III.

BISof50.Inthe last15minBISof 60. Anesthesiawas adjustedaccording toclinical parameters. Timefor spontaneouseye openingand extubation,PONV andintraoperative memory. Kreueretal.

(2005)10

1B 4 120/120 40/40 >18years,ASA I-III,orthopedic surgery.

BIS50andinthe last15minchange to60. Anesthesiawas adjustedaccording toclinical parameters. Timefor spontaneouseye opening, extubationand timeforleaving operationroom. Vretzakisetal.

(2005)11

1B 3 130/121 36/44 >18years,

myocardial revascularization orvalve replacementwith cardiopulmonary bypass,ejection fraction>45%.

BISunder60. Anesthesiawas adjustedaccording toclinical parameters.

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Table2 (Continued)

RCT EL J R/A I/C P I C O

Aiméetal. (2006)12

2B 1 140/125 34/54 Agebetween18

and80years,ASA I-III,urologic, orthopedic, abdominaland gynecological surgery.

BISbetween40 and60.

‘‘Blinded’’ monitor. Anesthesiawas adjustedaccording toclinical parameters.

Timefor spontaneouseye openingand traqueal extubation.

Ibraheimetal. (2008)13

2B 0 30/30 15/15 >18years,morbid obese,gastric bandsurgery.

BISbetween40 and60.

Anesthesiawas adjustedaccording toclinical parameters

Timeofeye openingupon verbalcommand, timefor extubationand dischargefrom PACU. Kamaletal.

(2009)14

2B 1 60/57 29/28 >18years,ASA

I-III,abdominal surgery

BISbetween50 and60.

Timefor spontaneouseye opening, extubation, orientationintime andplace,leaving operatingroom, dischargefrom PACUand intraoperative memory. Zhangetal.

(2011)15

1B 5 5.309/5.228 2.919/2.309 >18years,total intravenous anesthesia

BISbetween40 and60.

Intraoperative memory.

Chanetal. (2013)16

1B 3 921/902 450/452 >60years,elective non-cardiac surgery.

BISbetween40 and60.

Timefor spontaneouseye opening,timefor dischargefrom PACU,cognitive dysfunctioninthe postoperative period(oneweek andthreemonths later)and delirium. Radtkeetal.

(2013)17

1B 3 1.277/1.155 575/580 >60years BISbetween40 and60.

Cognitive dysfunctioninthe postoperative period(oneweek andthreemonths later)and delirium. ASA,AmericanSocietyofAnesthesiologistsPhysicalStatus;RCT,RandomizedClinicalTrial;EL,EvidenceLevel;J,Jadadscore;R/A, patientsrandomizedandanalyzed;I/C,interventiongroup/controlgroup;P,population;I,intervention;C,controlorcomparison;O, outcome.

spontaneouseyeopeningof0.28min(95%CI−0.75,0.20).

However, the statistically significant difference was lost (Fig.2).

The time for eye opening upon verbal command is

countedfromtheendof lastsuture,when theinhaled or

intravenous anesthetic is discontinued and the patient is

askedtoopenhiseyes.Therewasareductionintimetoeye openingatverbalcommandof0.63min(95%CI−1.30,0.05),

withan I2₌_67%,_with_no_{statistically}_significant _difference

(Fig.3).

The use of BIS reduced 1.18min in the time of

tra-cheal extubation(95% CI −1.65, −0.70), withan I2=79%.

In sensitivity analysis, when the study Kreuer et al.7

was removed, the time to tracheal extubation reduced

0.87min (95% CI −1.36, −0.38), with an I2=59%,

main-taining, therefore, a statistically significant difference (Fig.4).

Thecombinationofthreestudies1,2,14_demonstrated_that thetimefororientationintimeandplacereduced3.08min (95%CI−3.70,−2.45)withanI2=73%.Insensitivity

analy-sis,whenthestudyNelskyläetal.1_was_removed_we_have_a reductionof3.76min(95%CI−4.55,−2.97)withanI2=0%,

maintaining,therefore,astatisticallysignificantdifference (Fig.5).

WhenusingtheBIS,thetimeforthepatienttobeable

toget outofthe operatingroomandgotoPACUreduced

2.93min (95%CI−3.68,−2.18),withan I2=92%.In

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Table3 Full-textarticlesexcludedwithreasons.

Article Reasonofexclusion

Sebeletal.(1997)18 _Before_incision_tetanus_stimulation_was_applied_to_the_ulnar_nerve._Any_presence_of

movement,anesthesiawasdeepened.Intheabsenceofmovement,anesthesiawas maintained.Afterincisionanymovementwasconsideredforthedeepeningofanesthesia. Thestudygoesoutoffocus---BISinterventioncomparedtothecontrolgroup(consciousness guidedbyclinicalparametersonly).

Yli-Hankalaetal.(1999)19 _The_data_expression_of_the_outcomes_was_made_in_medians.

Mietal.(1999)20 _Patients_were_monitored_with_BIS_and_outcomes_were_analyzed_due_to_different_anesthetic

regimens.Thestudygoesoutoffocus---BISinterventioncomparedtothecontrolgroup (consciousnessguidedbyclinicalparametersonly).

Nakayamaetal.(2002)21 _All_patients_were_monitored_with_BIS_and_outcomes_were_analyzed_due_to_different_anesthetic

regimens(onlypropofolorpropofolandfentanyl).Thestudygoesoutoffocus---BIS interventioncomparedtothecontrolgroup(consciousnessguidedbyclinicalparameters only).

Lehmannetal.(2002)22 _All_patients_were_monitored_with_BIS_and_analyzed_outcomes_resulting_from_different

anesthetictechniques(withmanualpropofolinfusionvs.propofolinTargetControlled Infusion---TCI).Thestudygoesoutoffocus---BISinterventioncomparedtothecontrolgroup (consciousnessguidedbyclinicalparametersonly).

Paventietal.(2002)23 _All_patients_were_monitored_with_BIS_and_analyzed_outcomes_resulting_from_different

anesthetictechniques(manualpropofolinfusionvs.propofolinTCI).Thestudygoesoutof focus---BISinterventioncomparedtothecontrolgroup(consciousnessguidedbyclinical parametersonly).

Lehmannetal.(2003)24 _All_patients_were_monitored_with_BIS_(group_BIS₅₀_and_group_BIS_40)._The_study_goes_out_of

focus---BISinterventioncomparedtothecontrolgroup(consciousnessguidedbyclinical parametersonly).

Yamaguchietal.(2003)25 _All_patients_were_monitored_with_BIS_and_analyzed_outcomes_resulting_from_different

anestheticdrugsandtechniques(propofolgroup/ivinductionandsevofluranegroupwith inhalationalinductioninadultbythevitalcapacitytechnique).Thestudygoesoutoffocus ---BISinterventioncomparedtothecontrolgroup(consciousnessguidedbyclinicalparameters only).

Buyukkocaketal.(2003)26 _All_patients_were_monitored_with_BIS_and_outcomes_were_analyzed_due_to_different_anesthetic

drugs,fourdifferentmethodsofsedationassociatedwithtopicalanesthesia.Thestudygoes outoffocus---BISinterventioncomparedtothecontrolgroup(consciousnessguidedby clinicalparametersonly).

Forestieretal.(2003)27 _All_patients_were_monitored_with_BIS_and_analyzed_five_groups_with_different_{concentrations}_of

sufentanil.Thestudygoesoutoffocus---BISinterventioncomparedtothecontrolgroup (consciousnessguidedbyclinicalparametersonly).

Schneideretal.(2003)28 _All_patients_were_monitored_with_BIS_and_analyzed_four_different_anesthetic_regimens._The

studygoesoutoffocus---BISinterventioncomparedtothecontrolgroup(consciousness guidedbyclinicalparametersonly).

Schneideretal.(2003)29 _All_patients_were_monitored_with_BIS_and_analyzed_two_different_anesthetic_regimens._The

Liu(2004)30 _{Meta-analysis.}_The_criteria_for_inclusion_in_the_systematic_review_were_randomized_controlled

trials.

Baueretal.(2004)31 _All_patients_were_monitored_with_BIS_and_analyzed_two_different_anesthetic_regimens_(TCI_vs.

manualpropofolinfusion).TheBISwasusedbutisnotdescribedwhetheritwasblinded.The studygoesoutoffocus---BISinterventioncomparedtothecontrolgroup(consciousness guidedbyclinicalparametersonly).

Bestasetal.(2004)32 _All₅₀_patients_(two_groups_of₂₅₎_were_monitored_with_BIS_and_were_blinded,_with_analysis_of

twodifferentanestheticregimes.Thestudygoesoutoffocus---BISinterventioncomparedto thecontrolgroup(consciousnessguidedbyclinicalparametersonly).

Boztugetal.(2006)33 _Article_not_found.

Purietal.(2007)34 _All_patients_were_monitored_with_BIS,_with_analysis_of_two_different_types_of_propofol_infusion.

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Table3 (Continued)

Article Reasonofexclusion

Lindholmetal.(2008)35 _The_paper_analyzes_the_degree_of_proficiency_in_handling_the_BIS_by_nurses’_{anesthetists.}_The

Avidanetal.(2008)36 _In_the_control_group,_anesthesia_was_maintained_with_BIS_{‘‘blinded’’}_but_with_an_expired

fractionof0.7---1.3minimumalveolarconcentrationofinhaledanesthetic.

Bejjanietal.(2009)37 _All_patients_were_monitored_with_BIS_with_memory_processing_analysis._The_study_goes_out_of

focus--- BISinterventioncomparedtothecontrolgroup(consciousnessguidedbyclinical parametersonly).

Delfinoetal.(2009)38 _All_patients_were_monitored_with_BIS_or_cerebral_state_index,_with_analysis_of_propofol_infusion

withthesetwotypesofmonitoring.Thestudygoesoutoffocus---BISinterventioncompared tothecontrolgroup(consciousnessguidedbyclinicalparametersonly).

Kerssensetal.(2009)39 _Study_of_{intraoperative}_memory_and_retrieval_of_words_heard_during_the_{trans-operative,}

throughmemorytestspostoperatively.

Mashouretal.(2009)40 _Cohort_study._The_criteria_for_inclusion_in_the_systematic_review_were_randomized_controlled

trials.

Satishaetal.(2010)41 _Cohort_study._The_criteria_for_inclusion_in_the_systematic_review_were_randomized_controlled

trials.

Meybohmetal.(2010)42 _Protocol_study._The_criteria_for_inclusion_in_the_systematic_review_were_randomized_controlled

trials.

Leslieetal.(2010)43 _{Retrospective}_cohort_study._The_criteria_for_inclusion_in_the_systematic_review_were

randomizedcontrolledtrials.

Avidanetal.(2009)44 _Protocol_study._The_criteria_for_inclusion_in_the_systematic_review_were_randomized_controlled

trials.

Ellerkmannetal.(2010)45 _Inhalation_or_intravenous_anesthesia,_complemented_by_regional_anesthesia_(combined

anesthesia).Thestudygoesoutoffocus---BISinterventioncomparedtothecontrolgroup (consciousnessguidedbyclinicalparametersonly).

Yufuneetal.(2011)46 _The₃₈_patients_were_monitored_with_BIS_and_outcomes_were_analyzed_due_to_different

anestheticregimens,aswellasdifferentconcentrationsofremifentanil.Thestudygoesout offocus---BISinterventioncomparedtothecontrolgroup(consciousnessguidedbyclinical parametersonly).

Liuetal.(2011)47 _All_patients_were_monitored_with_BIS_and_outcomes_were_analyzed_due_to_different_anesthetic

regimens,targetcontrolledinfusionofpropofolvs.closed-loopmanagement.Thestudygoes outoffocus---BISinterventioncomparedtothecontrolgroup(consciousnessguidedby clinicalparametersonly).

Avidanetal.(2011)48 _The_control_group_was_adjusted_for_maintaining_an_expired_fraction_of_0.7---1.3_minimum

alveolarconcentrationofinhaledanesthetic.

Aiméetal.(2012)49 _The₁₀₂_patients_were_monitored_with_BIS_or_Entropy,_in_both_groups,_the_values_were_blinded,

andanesthesiawasconductedbyclinicalparameters.Thestudygoesoutoffocus---BIS interventioncomparedtothecontrolgroup(consciousnessguidedbyclinicalparameters only).

Mashouretal.(2012)50 _The_control_group_was_blinded,_but_adjusted_to_a_minimum_alveolar_{concentration}_of_inhaled

anestheticbyage.

Persecetal.(2012)51 _The_results_of_this_study_cannot_be_{meta-analyzed}_as_they_provide_no_standard_deviation.

Fritzetal.(2013)52 _{Retrospective}_cohort_study._The_criteria_for_inclusion_in_the_systematic_review_were

Villafrancaetal.(2013)53 _{Retrospective}_cohort_study._The_criteria_for_inclusion_in_the_systematic_review_were

BIS,bispectralindex.

haveareductionof4.89min(95%CI−5.95,−3.83)withan

I2₌_0%, _maintaining,_therefore, _{statistically}_significant

dif-ference(Fig.6).

The timefor patientstoachieve thedischarge criteria

inthe PACU(Aldrete-Kroulikmodified index)wasreduced

4.05min (95% CI−7.23,−0.87), withI2=91%.In

sensitiv-ity analysis, when removed the study Ibraheim et al.,13

wehaveareductionof22.35min(95%CI−31.01,−13.69)

withI2₌_20%,_maintaining_{statistically}_significant_difference

(Fig.7).

Therewasnostatisticallysignificantdifferencebetween theinterventionandcontrolintheevaluationofthe neces-sarytimetohospitaldischarge(95%CI,−22.08,30.52)with

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Study or Subgroup

Nelskylä KA 2001

Nelskylä KA 2001 Wong J 2002

Wong J 2002 Kreuer S 2003

Kreuer S 2003 Kreuer S 2005

Kreuer S 2005 Aimé I 2006

Aimé I 2006 Kamal NM 2009

Kamal NM 2009

Total (95% CI)

Heterogeneity: Chi2=34.57, df=6 (P<.00001); I2=83%

Heterogeneity: Chi2_{=2.29, df=5 (P=.81); I}2_{= 0%} Test for overall effect: Z=2.64 (P=.008)

Test for overall effect: Z=1.13 (P=.26)

275

235 241

281 100.0%

100.0% Bruhn J 2005

Bruhn J 2005

5

4

3.5 2.9 40 9.3 5.2 40

5.6 2.5 58

4.7 2.2 40

3.9 54

1.9 28

–10 –5 0 5 10

58 40 54 28 8

4.4 71 3.4

2.1 40

4.1 34

1.6 29

5.9

5.6 2.5 71

3.4 5.9 4.2

4.7 2.2

2.1 40

4.2 7.6

3.9 8

4.1 34

7.6 4.1

1.9 4.4

1.6 29

4.1

2.1 29

5 32 5

4.9 3.4 31

4 2.1 29 4.9 3.4 31

2 30

5 5 32 5 2 30

6.1% 2001

2002

2003 2005 2005

2006 2009

2001 2002 2003 2005 2005 2006 2009 10.6%

6.3% 20.5%

24.0% 7.1% 25.5%

6.5% 11.3% 0.0% 21.9% 25.6% 7.6% 27.2%

0.00 [–1.87, 1.87] –0.90 [–2.32, 0.52]

–5.80 [–7.65, –3.95] 0.30 [–0.72, 1.32] –0.50 [–1.44, 0.44]

–0.40 [–2.13, 1.33] –0.30 [–1.21, 0.61]

0.00 [–1.87, 1.87] –0.90 [–2.32, 0.52] –5.80 [–7.65, –3.95] 0.30 [–0.72, 1.32] –0.50 [–1.44, 0.44] –0.40 [–2.13, 1.33] –0.30 [–1.21, 0.61] –0.62 [–1.08, –0.16]

–0.28 [–0.75, 0.20]

Mean SDTotal Mean SD Total Weight Year

Year

IV, Fixed, 95% CI IV, Fixed, 95% CI

BIS Control Mean difference

Study or Subgroup Mean SDTotal Mean SD Total Weight IV, Fixed, 95% CI

BIS Control Mean difference

Mean difference

IV, Fixed, 95% CI Mean difference

BIS Control BIS Control

Figure2 Timeforspontaneouseyeopening(min).

TheincidenceofPONVwaslowerinanesthesiaconducted

withBIS,withariskreductionof12%(95%CI−0.22,−0.01)

withI2₌_61%,_which_was_{statistically}_significant₍_Fig.₉_).

Therewasnoriskreductionofcognitivedisordersinthe

post operatorywith 1 week after extubation, in patients

usingBIS(95%CI,−0.06,0.01,I2=0%).Therewasno

statis-ticallysignificant differencebetweentheinterventionand control(Fig.10).

The cognitivedisordersaftersurgeryat 3monthsafter

extubationhadariskreductionof3%(95%CI−0.05,−0.00),

andI2₌_52%,_which_was_{statistically}_significant₍_Fig.₁₁_).

There was a 6% reduction in the risk of delirium in

thepost operatoryin patients monitoredwithBIS(95% CI

−0.10, −0.03) I2=11%, which was statistically significant

(Fig.12).

TheuseofBIShadariskreductionof1%forthe intraoper-ativememory(Recall),astatisticallysignificantdifference (−0.01[95%CI,−0.01,−0.00])withI2=0%.The

intraoper-ativememoryis the awakeningconfirmedby the patient.

Itwasnotmade adifferentiation ofstudies withpatients

classified as low or high risk for intraoperative memory

(Fig.13).

Discussion

The use of monitoring with the BIS showed benefits by

reducingthetimetoextubationin0.87min,orientationin

timeandplacein 3.76min and leavingoperating roomin

4.89min.Patientshadareductionin22.35mintoreachthe

criteriafor PACU discharge. The combined results of the

studiesshowed thatthe incidenceof PONV riskreduction

of12%inpatientsBISmonitoring.

Cognitive disorders in postoperative patients with 1

week after extubation did not show statistically

signifi-cantdifference.However,therewasa3%reductioninthe

risk of cognitive disorders in the postoperative patients

Study or Subgroup

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

BIS Control Mean

Basar H 2003 8.25

18.5

6.8 2.1 15 8.66

2.6 15 15.9%

11.5 14 28 16 0.5%–9.50 [–19.00, 0.00]

–1.86 [–3.55, 0.17] 15

1.8 30 8.59 1 30 83.6% –0.34 [–1.08, 0.40] 2003

2008 2003 Puri GD 2003

Ibraheim O 2008

Heterogeneity: Chi2=5.97, df=2 (P=.05); I2=67%

–10 –5 0 5 10

Mean

SDTotal SDTotal Weight IV, Fixed, 95% CIYear IV, Fixed, 95% CI

BIS Control Mean difference Mean difference

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Study or Subgroup

Total (95% CI)

355 315 361 321 100.0% 100.0%

–1.18 [–1.65, –0.70]

–0.87 [–1.36, –0.38]

Nelskylä KA 2001 2

6.8 4.6 40 10.5 5.9 40 4.2%

4.4% 3.0% 6.5% 9.8% 21.8% 2.6% 7.2% 17.4% 40 16 40 40 58 54 15 28 6.1 3.2 5.3 4.4 2.4 9 2.9 2.3 8.3 6 9.7 5.4 6.3 14.2 11.8 4.8 4.1 40 14 40 40 71 34 15 29 4.3 2.9 2.2 3.5 5.1 2 2.1 6.5 7.2 4.1 4.4 6.6 11.1 9.26 4.3

2 32 3 2

2

6.8

4.6

40 10.5

5.9

6.1 3.2 5.3 4.4 2.4 9 2.9 2.3 8.3 6 9.7 5.4 6.3 14.2 11.8 4.8 4.1 40 14 40 40 71 34 15 29 4.3 2.9 2.2 3.5 5.1 2 2.1 6.5 7.2 4.1 4.4 6.6 11.1 9.26 4.3

2

32 3

2 30 40 40 16 40 40 58 54 15 28 30 23.0% 24.6% 4.5% 4.7% 3.2% 0.0% 10.5% 23.4% 2.8% 18.6%

–10 –5 0 5 10

7.7%

–1.00 [–2.00, –0.00]

–1.00 [–2.00, –0.00] –3.70 [–6.02, –138]

–3.70 [–6.02, –138] –1.80 [–4.08, 0.48] 1.20 [–1.54, 3.94]

–5.60 [ –7.47, –3.73] –1.00 [–2.52, 0.52]

0.30 [–0.72, 1.32] –3.10 [–6.05, –0.15] –2.54 [–4.32, –0.76] –0.50 [–1.64, 0.64]

2001 2003 2003 2003 2003 2005 2005 2006 2008 2009 2001 2003 2003 2003 2003 2005 2005 2006 2008 2009 –1.80 [–4.08, 0.48]

1.20 [–1.54, 3.94]

–5.60 [ –7.47, –3.73]

–1.00 [–2.52, 0.52] 0.30 [–0.72, 1.32]

–3.10 [–6.05, –0.15] –2.54 [–4.32, –0.76]

–0.50 [–1.64, 0.64] Luginbühl _{M, 2003 (a)}

Luginbühl M, 2003 (b) Puri GD 2003 Kreuer S 2003 Kreuer S 2005 Bruhn J 2005 Aimé I 2006 Ibraheim O 2008 Kamal NM 2009

Nelskylä KA 2001 Luginbüh_{l M, 2003 (a)}

Luginbühl M, 2003 (b)

Puri GD 2003 Kreuer S 2003

Kreuer S 2005 Bruhn J 2005

Aimé I 2006 Ibraheim O 2008

Kamal NM 2009

Heterogeneity: Chi2_{=42.58, df=9 (P<.00001); I}2_=79%

–10 –5 0 5 10

Test for overall effect: Z=4.83 (P<.00001)

Heterogeneity: Chi2_{=19.65, df=8 (P=.01); I}2_=59% Test for overall effect: Z=3.45 (P=.0006)

Mean SD TotalMean SDTotal Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI

Study or Subgroup MeanSD TotalMeanSDTotal Weight IV, Fixed, 95% CIYear IV, Fixed, 95% CI

BIS

Control Mean difference Mean difference

BIS Control

Figure4 Timetotrachealextubation(min).Luginbühl(2003)studiedwithinasingleoutcome,twodifferentanestheticregimens withpropofol(a)anddesflurane(b).

3 months after extubation. There was a 6% reduction in

theriskof deliriumincidenceof postoperativeinpatients

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-riashowedaheterogeneitythatwassoonnoticed.Factors

related toanesthetic technique,the patientand the

sur-gical procedure wereobserved. Studiesthat analyzed the

consumptionofanesthetics showednostandardized

meas-Study or Subgroup

Mean

SDTotal MeanSDTotal Weight IV, Fixed, 95% CIYear IV, Fixed, 95% CI

BIS

Control Mean difference Mean difference

Study or Subgroup Mean SDTotal MeanSDTotal Weight IV, Fixed, 95% CIYear IV, Fixed, 95% CI

6 9.5 7.4 2 3.1 1.5 32 29 29 3 2 3.8 13.1 11.2 1.9

30 38.8% –2.00 [–3.00, –1.00] –3.60 [–5.35, –1.85] –3.80 [–4.69, –2.91]

2001 2002 2009 2001 2002 2009 12.6% 48.6%

–10 –5 0 5 10

28 31 Kamal NM 2009

2 9.5 7.4 2 3.1 1.5 32 29 29 3 2 3.8 13.1 11.2 1.9

30 0.0% –2.00 [–3.00, –1.00] –3.60 [–5.35, –1.85] –3.80 [–4.69, –2.91] 20.6%

79.4% 28 31 Kamal NM 2009

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

Heterogeneity: Chi2_{=7.36, df=2 (P=.03); I}2_=73% Test for overall effect: Z=9.71 (P<.00001)

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

Heterogeneity: Chi2_{=.04, df=1 (P=.84); I}2_=0%

Test for overall effect: Z= 9.28 (P<.00001) –10 –5 0 5 10

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Study or Subgroup Mean SDTotalMean SDTotal Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI

40 40

40

40 Kreuer S 2003

Kreuer S 2005

9.4 8.4 7

1.9 2.4 3.2

29

40

40 29

14.1 9.4 12.4

2.8 2.4 5.7

–4.70 [–5.95, –3.45] –1.00 [–2.05, 0.05] –5.40 [–7.43, –3.37]

2009 2005 2003

–4.70 [–5.95, –3.45] –1.00 [–2.05, 0.05] –5.40 [–7.43, –3.37] 35.9%

72.5% 0.0% 27.5% 50.5% 13.6%

28 40 40 28 Kamal NM 2009

Kreuer S 2003

Kreuer S 2005 Kamal NM 2009

Total (95% CI) 109 108100.0% –2.93 [–3.68, –2.18]

Heterogeneity: Chi2_{=26.39, df=2 (P<.00001); I}2_=92% Test for overall effect: Z=7.68 (P<.00001)

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

Heterogeneity: Chi2_{=.33, df=1 (P<.56); I}2_=0%

Study or Subgroup Mean SDTotalMean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI

–10 –5 0 5 10

Figure6 Timeforleavingoperationroom(min).

Wong J 2002 111 30 29 123 48 31 2.5% –12.00 [–32.12, 8.12]

Wong J 2002 111 30 29 123 48 31 18.5% –12.00 [–32.12, 8.12] 86.5%

15 4.81 31 15 4.74

29.8 –1.20 [–4.62, 2.22]

Ibraheim O 2008

0.0% 15 4.81 31 15 4.74

29.8 –1.20 [–4.62, 2.22]

Ibraheim O 2008

11.0% 28 21.5 78.6 29 14.7

53.9 –24.70 [–34.29, –15.11]

2002 2008 2009

2002 2008 2009 Kamal NM 2009

81.5% 28 21.5 78.6 29 14.7

53.9 –24.70 [–34.29, –15.11]

Kamal NM 2009

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

Heterogeneity: Chi2_{=21.07, df=2 ( P<.0001); I}2_=91%

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

Heterogeneity: Chi2_{=1.25, df=1 ( P=.26); I}2_=20%

Study or Subgroup Mean SDTotalMean SD Total Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI

Study or Subgroup Mean SDTotalMean SDTotal Weight IV, Fixed, 95% CI Year IV, Fixed, 95% CI

BIS Control

–100 –50 0 50 100

BIS Control

–100 –50 0 50 100

Figure7 TimefordischargefromPACU(min).

uresthatenabledtheselection ofatleasttwostudiesfor

themeta-analysis.

The study Ibraheim et al.13 _involved _morbidly _obese

patients. Three studies were conducted exclusively with

patientsover60yearsofage.2,16,17

Purietal.6_and_Vretzakis_et_al.11_studied_patients under-goingcardiacsurgerywithextracorporealcirculation.

Mylesetal.8_studied_patients_with_at_least_one_high-risk

factor for awakening with intraoperative memories (high

risk heart surgery, cesarean sections, hypovolemic shock,

rigidbronchoscopy,cardiovascularinstabilityandexpected hypotensionduringsurgery,lungdiseaseinadvancedstages, historicalofawakeningwithintraoperativememories,

dif-ficult airway, high consumption of alcohol, chronic use

Study or Subgroup Mean SDTotal Mean SD Total Weight IV, Fixed, 95% CI IV, Fixed, 95% CI

Nelskylä KA 2001

Ahmad S 2003

306 85 32 298 124 30 24.4%

203 78 49 200 74 48 75.6%

8.00 [–45.26, 61.26]

3.00 [–27.25, 33.25]

Year

2001

2003

Total (95% CI)

Heterogeneity: Chi2=0.03, df=1 (P=.87); I2=0%

81 78 100.0% 4.22 [–22.08, 30.52]

–100 –50 0 50 100

BIS Control

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Study or Subgroup EventsTotal EventsTotal Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI

BIS Control Risk difference Risk difference

Nelskylä KA 2001 Bruhn J 2005

5 32 12 30 32.7%

6 71 8 58 67.3%

–0.24 [–0.46, –0.03] –0.05 [–0.16, 0.06]

Year

2001 2005

Total (95% CI)

Total events

Heterogeneity: Chi2=2.59, df=1 (P=.11); I2=61% Test for overall effect: Z=2.22 (P=.03)

103

11

88

20

100.0% –0.12 [–0.22, –0.01]

–1 –0.5 0 0.5 1

BIS Control

Figure9 Postoperativenauseaandvomiting(PONV)---n(%).

Study or Subgroup Events Total Events Total Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI

Chan 2013 Radtke 2013

98 70

450 104 452 43.9% –0.01 [–0.07, 0.04]

575 90 580 56.1% –0.03 [–0.07, 0.01]

Total events

Heterogeneity: Chi2_{=.39, df=1 (P=.53); I}2_=0% Test for overall effect: Z=1.45 (P=.15)

168 194

–1 –0.5 0 0.5 1

BIS Control

Total (95% CI) 1025 1032 100.0% –0.02 [–0.06, 0.01]

Figure10 Cognitivedisordersinthepostoperativeperiod(1weekafterextubation)---n(%).

46 21

450 66 452 43.9% –0.04 [–0.09, –0.00]

575 28 580 56.1% –0.01 [–0.03, 0.01]

Total events

Heterogeneity: Chi2_{=2.08, df=1 (P=.15); I}2_=52% Test for overall effect: Z=2.21 (P=.03)

67 94

–0.5 –0.25 0 0.25 0.5

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

Figure11 Cognitivedisordersinthepostoperativeperiod(3monthsafterextubation)---n(%).

Study or Subgroup EventsTotal EventsTotal Weight M-H, Fixed, 95% CI M-H, Fixed, 95% CI

70 95

450 109 452 43.9% –0.09 [–0.14, –0.03] 575 28 580 56.1% –0.05 [–0.09, –0.00]

Year

2013 2013

Total events

Heterogeneity: Chi2_{=1.12, df =1 (P=.29); I}2_=11%

165 233

–1 –0.5 0 0.5 1

BIS Control

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

Figure12 Postoperativedelirium---n(%).

Puri GD 2003 Myles PS 2004 Bruhn J 2005 Kamal NM 2009 Zhang C 2011

0 2 0

14 1 16 0.4% –0.06 [–0.23, 0.10] 1225

71 29 2919 0 4

11 0 0 15

1238 58 28 2309

31.4% 1.6% 0.7% 65.8%

–0.01 [–0.01, –0.00] 0.00 [–0.03, 0.03] 0.00 [–0.07, 0.07] –0.01 [–0.01, –0.00]

2003 2004 2005 2009 2011

Total events

Heterogeneity: Chi2_{=1.04, df=4 (P=.90); I}2_=0%

6 27

–0.1 –0.05 0 0.05 0.1

BIS Control

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

Year

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of benzodiazepines or opioids and therapy with protease inhibitors).

The outcomes analyzed with continuously variable

relatedtothe timeof recovery anddischarge ofpatients

were:timeforspontaneouseyeopening,timeforeye

open-ing upon verbal command, time for extubation, time for

orientation in time and place, time for leaving operating

room, timefor PACUdischarge and time for hospital

dis-charge.

The outcomes of dichotomous variable, related to

adverseeventswerePONV,cognitivedisordersinthe

post-operative 1 week after extubation, cognitive disordersin

thepostoperative3monthsafterextubation,postoperative

deliriumandintraoperativememory.

Some primary studies contributed only one outcome

analyzed.3---5,11,15

The individualizationof outcomesderivedfromstudies

involvingbalancedanesthesiaortotalintravenous

anesthe-siawasnotmade.

Clinically,thecostofimplementationofBISmonitoring canbejustifiedbyallowingadvantagesinthemaintenance ofambulatorysurgeriesaswellasinthetechniquesofearly

awakening and especially it can reduce the incidence of

adverseevents.

The cost of thedisposable electrodeis a causeof

dis-cussionaboutthevalueinuseofBIS.Thus,itisimportant

the active participation of professionals, primarily with

healthadministrators,indevelopingapolicyplanthat opti-mizeresourcesandgivegreatersafetyandcomfortforthe patients.

Sofar,thereisnogoldstandardtospantheentire spec-trumofanestheticeffectonthecentralnervoussystem,and theBISisundoubtedlythemoststudied,butisoneofmany

monitorsderivedfromEEGusednowadays.Monitoringthe

depthof anesthesiaasnewtechnologyisin itsbeginning. Thenewboundaryistheindividualizationofmonitoringthe hypnoticanditseffectsonthecentralnervoussystem.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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