Rev. Bras. Anestesiol. vol.65 número5

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REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

OfficialPublicationoftheBrazilianSocietyofAnesthesiology

www.sba.com.br

MISCELLANEOUS

Correlation

of

bispectral

index

(BIS)

monitoring

and

end-tidal

sevoflurane

concentration

in

a

patient

with

lobar

holoprosencephaly

Dario

Galante

a,∗

,

Donatella

Fortarezza

a

,

Maria

Caggiano

a

,

Giovanni

de

Francisci

b

,

Dino

Pedrotti

c

_,

_Marco

_Caruselli

d

a_University_Department_of_Anesthesia_and_Intensive_Care,_University_Hospital_Ospedali_Riuniti_of_Foggia,_Italy

b_Department_of_Anesthesia_and_Intensive_Care,_Agostino_Gemelli_Hospital,_Catholic_University_of_the_Scared_Heart,_Rome,_Italy c_Department_of_Anesthesia_and_Intensive_Care,_S._Chiara_Hospital,_Trento,_Italy

d_Department_of_Anesthesia_and_Intensive_Care,_La_Timone_Children’s_Hospital,_Marseille,_France

Received27March2014;accepted3July2014 Availableonline25October2014

KEYWORDS

Holoprosencephaly;

Bispectralindex;

Sevoflurane; Seizures

Abstract

Objective: Thebispectralindex(BIS)isaparameterderivedbyelectroencephalography(EEG) whichprovidesadirectmeasurementoftheeffectsofsedativesandanestheticsonthebrain andoffersguidanceontheadequacyofanesthesia.TheliteraturelacksstudiesonBISmonitoring inpediatricpatientswithcongenitalbraindiseaseundergoinggeneralanesthesia.

Clinicalfeatures:A13-year-oldchildweighing32kg,sufferingfromlobarholoprosencephaly, underwentsurgeryinwhichthebispectralindex(BIS)monitoringthedepthofanesthesiashowed anabnormalresponse.DetailedanalysisofthetrendsofBISvaluesinthedifferent observa-tiontimesdemonstratedsuddenfallsandrepetitivevaluesofBISlikelyrelatedtorepetitive epileptiformelectricalactivitycausedbysevoflurane.

Conclusion: TheBISisaveryusefulmonitoringtoolforassessingthedegreeofdepthof anesthe-siaandtoanalyzetheelectroencephalographicvariationsofanesthetics.Particularattention shouldbegiventopatientswithcongenitaldisordersofthecentralnervoussysteminwhich theBISmaygiveabnormalresponsesthatdonotreflectanaccurateassessmentofthedepth ofanesthesia.

∗_{Corresponding}_author.

E-mail:dario.galante@tin.it(D.Galante). http://dx.doi.org/10.1016/j.bjane.2014.07.003

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PALAVRAS-CHAVE

Holoprosencefalia;

Índicebispectral;

Sevoflurano; Convulsões

Correlaçãoentremonitoraçãodoíndicebispectral(BIS)econcentraçãoexpiradade sevofluranoempacientecomholoprosencefalialobar

Resumo

Objetivo:Oíndice bispectral(BIS) éum parâmetroderivadopor eletroencefalografia(EEG) queforneceumamedidadiretadosefeitosdesedativoseanestésicosnocérebroeorientação sobreaadequaçãodaanestesia.AliteraturacarecedeestudossobreamonitoraçãodoBISem pacientespediátricoscomdoençacerebralcongênitasubmetidosàanestesiageral.

Característicasclínicas: Criança de13anosdeidade,pesando32kg,comholoprosencefalia lobar,foisubmetidaàcirurgiaemqueamonitoraçãodaprofundidadedaanestesiacomouso doBISmostrouumarespostaanormal.AanálisedetalhadadastendênciasdosvaloresdoBISnos diferentestemposdeobservaçãomostrouquedassúbitasevaloresrepetitivosdoBIS, provavel-menterelacionadosàatividadeelétricaepileptiformerepetitivacausadaporsevoflurano. Conclusão:OBISéumaferramentademonitoraçãomuitoútilparaavaliarograude profundi-dadedaanestesiaeasvariaçõeseletroencefalográficasdosanestésicos.Atençãoespecialdeve serdedicadaaospacientescomdoençascongênitasdosistemanervosocentralnosquaisoBIS podeapresentarrespostasanormaisquenãorefletemaavaliaçãoprecisadaprofundidadeda anestesia.

Introduction

Holoprosencephaly

Holoprosencephaly(HPE)is acomplexbrain malformation

inwhichthereisanincompleteseparationoftheforebrain

betweenthe18thand28thdayofintrauterinelife,affecting

boththe forebrainandtheface,causing neurologicaland

facialdefectsofvaryingseverity.1

Ithasaprevelanceof1in250duringearlyembryo devel-opment,and1in10,000to1in20,000atterm.

Three classic forms of progressive severity have been described, classified according to their anatomical fea-tures:HPElobar,semi-lobar,andalobar.Amildersubtype, knownasmiddle interhemisphericvariant (MIH), wasalso identified. The HPE phenotype also includes aprosence-falia/atelencefalia(the most severe sign),schizencephaly andsepto-preopticHPE.The lesssevereformsaredefined microforms,characterizedbydefectsinthemidline,inthe absenceofbrainmalformationtypicalofHPE.However,the diseaseischaracterizedbyacontinuousspectrumof abnor-malseparation of thecerebral hemispheres ratherthana distinctsubdivisionoftheseformswhichpresent,however, significantinclinicalinter-andintra-familialvariability.In manycases,thereisacorrelationbetweentheseverityof facialabnormalitiesandbrainanomaly(withtheexception of mutationcases in the ZIC2 gene). In descending order of severity the main facial features are cyclopia, a pro-boscis,premaxillaryagenesis,acleftlip,coloboma,retinal dysplasia,choanalstenosis, stenosisofthepyriformsinus, hypotelorism, asingle median maxillary incisor,and even anormalface.Severeforms(especiallyinthepresenceof achromosomalabnormality)areoften fatalandmortality is associated withthe severity of the brain malformation and associated defects. In children who survive, a broad

spectrumofrelatedsignshasbeendescribed: developmen-tal delay,hydrocephalus, motordeficits, eatingproblems, motordysfunction,epilepsy,andhypothalamicdysfunction. Endocrine disorders from pituitary abnormalities, such as centraldiabetes,arecommon.

Lobar holoprosencephaly is the milder classic form of holoprosencephaly. It is characterized by the separation between the leftand right cerebral hemispheres and lat-eralventricleswithajunctionalongthefrontalneocortex, particularly rostrally and ventrally. Approximately 19% of patientswithlobarHPEhavetheshape.

Thebispectralindex

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the optimal quantity of drugs for each patient so as to maintaintheBISvaluewithinarangethatguaranteesa non-verbalresponsetostimuliandthelowprobabilityofexplicit memory. Prospective studieshave shown that a BIS main-tained between 40 and 60 ensures an adequate hypnotic stateduringanesthesia.

The reliabilityandaccuracy ofBISmonitoringfor pedi-atricpatientsisstillbeingstudied,especiallyinveryyoung children, neonates, andinfants. In addition,thereareno studiesontheuseoftheBISinpediatricsubjectssuffering from rare congenital diseases of the central nervous sys-tem.AwidevariabilityintheBISvalueshasbeenobserved inmanychildrenwithrespecttothedosagesofanesthetics used.

Case

report

One13-year-oldchildweighing 32kg, sufferingfromlobar holoprosencephaly,wasbroughttoourattentionfor orchi-dopexysurgery.Thechildwasindrugtreatmentwithsodium valproate,clorazepam,levothyroxinesodium,somatropin, anddesmopressin.The inductionwasmadeviainhalation, without premedication, through a mixture of air, oxygen, andsevoflurane ata concentrationof 6%andFiO2 of 0.4,

immediately after a peripheral vein wascannulated, fol-lowed by the administration of 2␮g/kg of fentanyl and

cisatracurium 0.15mg/kg. Then a ProSeal laryngeal mask airway (PLMA) size 2.5 wasinserted. The child was then connectedtomechanicalventilationwithamixtureofair, oxygenandend-tidalconcentrationofsevoflurane3%with FiO2of0.4andsubsequentlyreducedto2%,asaresultofthe

evaluationwithbispectralindex,allowing perfect adapta-tiontoartificialventilation.Allroutinehemodynamic and respiratory monitoring systems were applied: blood pres-sure,ECG,ETCO2andSpO2.Fromthemomentofinduction

adhesive front sensors were applied for the detection of thebispectralindex(BISVistaMonitoringSystemTM_,_Aspect

MedicalSystem,USA),recordingthetrendsfortheduration ofthesurgeryuntiltheawakeningofthechild.TheBIS val-ues were recordedat thefollowing times:Ti (induction), Tsis (surgical incision of the skin), T5 (5min after incision

oftheskin),Tsevo2 (afterreductionoftheconcentrationof

end-tidalsevoflurane2%),andTrecovery(thecessationofthe

administrationofsevofluraneanduponwaking).

Duringtheinductionphasewithsevofluraneat6%(Ti)the

BISrecordedamedianvalueof27.5±3.5DS(Fig.1).Atthe timeofthesurgicalincisionoftheskin,withaconcentration ofend-tidalsevolfuraneat3%(Tsis)amedianof41.5±4.3

DS(Fig.1),and5min aftertheskinincision(T5)amedian

of26.0±4.2DS(Fig.2).Having consideredthe aboveBIS valuestoolowcomparedtothe40---60standardrelativeto an appropriate anesthesiaplan,it was decidedtoreduce the end-tidal concentration of sevoflurane to 2% (Tsevo2).

During this time we recorded BIS values of 26.5±5.3 SD (Fig.3).Attheendofthesurgery,about75minafter induc-tion,westoppedtheadministrationofsevoflurane(Trecovery)

until the child woke up. The median BIS values recorded were29.5±8.1DSwitha maximumof47 andaminimum of17(Fig.4).ThetotalBISvaluesrecordedrelatedtothe wholedurationoftheoperationshowedanexcessivedepth ofanesthesiawithmedianvaluesof27±6.3SD(Fig.5).

50

45

40

35

30

25

20

15

10

5

0

Time

Tsis Ti

BIS values

Figure1 BISvaluesatthetimeofinduction(Ti,27.5±3.5 DS)andsurgicalincisionoftheskin(Tsis,41.5±4.3DS).

Theawakeningtookplacewithoutcomplicationsandin theabsenceofagitationorseizures.Throughoutthe dura-tionofthesurgeryrespiratoryandhemodynamicparameters wereallwithinthenormalrange:heartrate81.3±3.3SD, systolicbloodpressure101.3±2.0SD,diastolicblood pres-sure 52.0±2.3 SD, mean arterial pressure 68.5±1.8 SD (Fig. 6).Duringthe time(Tsevo2),an

electroencephalogra-phywasrecorded(EEG)thatdemonstratedanepileptiform EEGactivitywithspikes(Fig.7).

50

45

40

35

30

25

20

15

10

5

0

Time

T5

BIS values

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40

35

30

25

20

15

10

5

0

Time

Tsevo2

BIS values

Figure 3 BIS values with 2% end-tidal sevoflurane (Tsevo2, 26.5±5.3SD).

50

45

40

35

30

25

20

15

10

5

0

Time Trecovery

BIS values

Figure 4 BIS values during the recovery of the patient (Trecovery,29.5±8.1DS).

Discussion

Theliterature lacksstudies onBISmonitoringin pediatric patientswithcongenital braindisease undergoinggeneral anesthesiafor surgery. Consequentlyit is very difficult to interpret the mechanisms by which such monitoring may besubjecttochangeor alterationunderanesthesia.5 _The BISexpressesthedepthofanesthesiawithanumericvalue ranging from0 (deepanesthesia) to100 (awake patient), while values between 40 and 60 are considered ideal for anadequate surgical anesthesia. Inprinciple, theBIS val-uesrecordedinthepediatricageareinverselyproportional totheconcentrationofend-tidalsevofluraneandcorrelate

50

45

40

35

30

25

20

15

10

5

0

BIS values

Time

Total duration of procedure

Figure5 BISvaluesduringallthetimeofsurgicalprocedure (27±6.3SD).

120

100

80

60

40

20

0

mmHg/HR

HR SBP DBP MAP

Time

Figure6 Hemodynamic parametersrecordedduringallthe timeofsurgicalprocedure(HR,heartrate;SAP,systolicarterial pressure;DAP,diastolicarterialpressure;MAP,middlearterial pressure).HR81.3±3.3SD,SBP101.3±2.0SD,DBP52.0±2.3 SD,MAP68.5±1.8SD.

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muchbetterwithchangesinbloodpressureandheartrate. Inaddition,theend-tidalconcentrationofsevofluranewhich correspondstoaBISof50(95%)ishigherinchildrenunder two years comparedto those who are older (1:55 versus 1:25%).IntherecoveryphasechangesintheBISaremore progressiveinolderchildrencomparedtothesmallerones whichshowinsteadanon---offprofile.6

Inourcase,despitehavingusedhigherend-tidal sevoflu-rane concentrations compared to those indicated above, fromthetimeofinductiontotheawakeningstage,thetotal BISvalues recordedrelated totheduration of the opera-tionshowedanexcessivedepthofanesthesiawithmedian valuesof27±6.3SD.Thisdatacanbeunderstandable dur-ing theearly stages of anesthesia, induction inparticular (Ti27.5±3.5DS),whentheconcentrationsof sevoflurane

needtobehigher.Insubsequentstages,especiallyatTsevo2

time,wewouldhaveexpectedanincreaseintheBISvalues afterreducing theend-tidalconcentrationof sevoflurane. In contrast,theBIS recordedmedian valuesparadoxically lower(Tsevo226.5±5.3DS).Similarly,duringtheawakening,

BISvalueswereratherlow (Trecovery29.5±8.1 DS)instead

of nearing60 which normallyindicates the resumptionof patientconsciousness.TherelativelyhigherBISvalue,and thus closer tothe rangeof 40---60, wasfound onlyat the moment of the incision of the skin (Tsis 41.5±4.3 DS)

although the BIS has no specificity in the prediction of responsetonociceptivestimuliasitisavaluemoreorless insensitivetonarcoticswhilereflectingthehypnoticstate. The mechanism and the possible causes of this abnor-mal response can be demonstrated, in our opinion, in a detailedanalysisof thetrends of BISvaluesinthe differ-entobservationtimes.Inparticular,inT5,Tsevo2,andTrecovery

(Figs.2---4)weexperiencedrapidvariabilitywithsuddenfalls andrepetitivevaluesofBIS.Therewasnotartifacts,andthe patientwasotherwisewell curarized:signal qualityindex (SQI),electromyograph(EMG),suppressionratiovalue(SRV) showedagoodqualityofsignal.

This fact brings us to another published case report, although onan adult patient,in whichsevoflurane deter-mined repetitive epileptiform electrical activity with suddenandrapidfalloftheBISvalues,whichwereresolved byadministeringantiepilepticdrugsduringsurgery.7

It is well-documented that sevolfurane can stimulate epileptogenic activity8---10 _and _the electroencephalogra-phy recorded during the time Tsevo2 demonstrated us an

epileptiformEEGactivitywithspikes;inourcaselobar holo-prosencephalyisadiseasethatisaccompaniedbyepilepsy. Althoughthechildwasalreadybeingtreatedwith medica-tionsforanunderlying disease,wemustassumethatthey werenotabletolimittherapidchangesobservedwiththe BISandsevofluranehasplayedanimportantrole.Wehave notusedanti-epilepticdrugsthatwouldbeusefulasex adiu-vantibuscriteriontodemonstratethenatureofthechanges inBISvalues.Inreality,fromaclinicalstandpointno con-vulsionswereobserved duringtheoperationor duringthe awakeningphase.Itislikelythattheepilepticactivitywas

aneuroelectricmanifestationdetectedbytheBIS.Finally, thegoodhemodynamic stability throughout theoperation confirmsthattheconcentrations ofsevofluranearebetter relatedtotheBISthanthevariationsofbloodpressureand heartrateinthepediatricpatient.

Conclusions

The BIS is a very useful monitoring tool for assessing the degree of depth of anesthesia and to analyze the elec-troencephalographic variations of anesthetics. Particular attentionshould begiventopatients withcongenital dis-ordersofthecentralnervoussystem inwhichtheBISmay give abnormal responses that do not reflect an accurate assessmentofthedepthofanesthesia. Thisisparticularly importantinthecaseofhighconcentrationsofsevoflurane thatmayresultinepileptogenicaction.Inthesecasesthe choiceofadifferentanesthetictechniqueshouldbetaken intoseriousconsideration.

Conflicts

of

interest

Theauthordeclaresnoconflictsofinterest.

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