JPediatr(RioJ).2017;93(5):439---441
www.jped.com.br
EDITORIAL
Brain-focused
care
in
the
neonatal
intensive
care
unit:
the
time
has
come
夽
,
夽夽
Cuidado
neurológico
na
unidade
de
terapia
intensiva
neonatal:
chegou
a
hora
Krisa
Page
Van
Meurs
∗,
Sonia
Lomeli
Bonifacio
StanfordUniversitySchoolofMedicine,DepartmentofPediatrics,DivisionofNeonatalandDevelopmentalMedicine, PaloAlto,California,UnitedStates
Survivalrates for extremelypreterm infants andfor criti-callyilltermnewbornshaveimprovedsteadilyoverthelast several decades;however, these samebabies continue to experiencehighrates ofadverseneurodevelopmental out-comeswithlife-longimpact.Brain-focusedcareisadesired evolutioninneonatalcareafterdecadesoffocusonsurvival and extending the limits of viability. Neonatal neurology andneonatalneurocriticalcarearegrowing subspecialties thatseektobetteraddresstheneedsofneonateswith,or at riskfor, neurologicalcompromisebyintegrating neona-tal intensive care practices withfocused neurologiccare. The development and application of bedside neuromoni-toringhassignificantly contributedtothe enhancedfocus andourabilitytobothmonitorandprovidecareforthese vulnerable newborns. Non-invasive neurologic monitoring with techniques such as amplitude-integrated electroen-cephalography(aEEG)andnear-infraredspectroscopy(NIRS) allowscreeningandassessmentatthebedsidebyneonatal nursesandphysicians.
In thisissue ofthe JornaldePediatria,Varianeetal.1
describedaprospectivecohortstudyof23preterminfants
夽
Pleasecitethisarticleas:VanMeursKP,BonifacioSL. Brain-focusedcareintheneonatalintensivecareunit:thetimehascome. JPediatr(RioJ).2017;93:439---41.
夽夽
SeepaperbyVarianeetal.inpages460---6.
∗Correspondingauthor.
E-mail:[email protected](K.P.VanMeurs).
less than 31 weeks gestationand 17 term newborns with
hypoxicischemicencephalopathy(HIE).Subjectswere
mon-itored withaEEG withassessment of background activity,
sleep---wakecycling(SWC),andpresenceofseizuresondays
1,2,and 3of life.In thepreterm group,abnormal
back-groundpatternandabsenceofSWCweretheaEEGfindings
associated with death or severe abnormalities on cranial
ultrasound. Abnormal background pattern was defined as
discontinuous low-voltage, burst suppression, continuous
lowvoltage,orflattracing.InthetermHIEgroup,seizures
andlongertimetonormalbackgroundtracingweretheaEEG
featuresassociatedwithdeathandMRIabnormalities.
TheresearchfindingspresentedbyVarianeetal.1addto
agrowingbodyofevidencesupportingtheuseofaEEGinthe
neonatalintensivecareunit.aEEGwasfirstdevelopedasa
tooltoassessthedepthofanesthesiaduringsurgery,
pro-vidingreal-timeassessmentofbrainactivityduringexposure
toanestheticagents.aEEGmonitoringdevicesnowdisplay
botha limited channelEEGaswell asa time-compressed
aEEGtraceallowingevaluationofbackgroundactivity,
dis-playing changes in background activity over time, and
screening for seizures. The first background classification
system,developedbyHellström-Westas,wasbasedon
pat-tern recognition to distinguish between five categories:
continuousnormal voltage, discontinuous normal voltage,
burstsuppression,continuouslowvoltage,andflattracing.2
AnotherclassificationmethodwasdevelopedbyalNaqueeb
basedonsimplevoltagecriteria.3Amoreconsistent
inter-pretationwasfound withthe simplevoltage criteriathan
withpatternrecognitioninonestudy4;however,thepattern
http://dx.doi.org/10.1016/j.jped.2017.03.002
440 VanMeursKP,BonifacioSL
recognitionclassificationsystemremainswidelyused.aEEG
has been shown to have good agreement with EEG
back-ground classificationwhenstudied in term newborns with
HIE,5 but no similar comparison has been performed in
preterminfants.Terminfantswithneonatalencephalopathy
wereoneofthefirst diagnosticgroupstobestudied with
aEEG.NumerousearlyaEEGstudiesperformedpriortouse
oftherapeutichypothermiadeterminedthatabnormal
back-groundpatternsareapredictorofoutcomeinneonateswith
HIE.Accordingly,abnormalaEEGbackgroundpatternatless
than6hofagewasusedasaneligibilitycriteriainseveral
trialsoftherapeutichypothermiaforHIE.6,7Thoresenetal.
performedanimportantstudyof continuousaEEGfor 72h
interm infantswithHIEin cooled(n=43)and non-cooled
(n=31) newborns.8 Recovery time to normal background
patternwasfoundtobethebestaEEGpredictorofabnormal
outcomeat18monthsofage.Inthisanalysis,normal
back-groundpatternincludedbothcontinuousnormalvoltageand
discontinuousnormalvoltage.Infantswithagoodoutcome
treated with normothermia had normal tracings by 24h,
whereasthosetreatedwithhypothermiahadnormal
trac-ingsby48h.Massaroconfirmedthehighpositivepredictive
value of abnormalaEEG background for adverse outcome
at hospital discharge.9 SWC were present at the time of
rewarmingin 58%and allhada favorableoutcome, while
nobabies withadverse outcome had SWC at the time of
rewarming.Ameta-analysisofeightstudiesinterminfants
withHIEconcludedthataEEGhadanoverallsensitivityof
91%(95%CI:87---95)andspecificityof88%(95%CI:84---92)to
predictpooroutcome.10Arecentmeta-analysisof31aEEG
studies concluded that burst suppression, continuous low
voltage,andflattracingaretheaEEGbackgroundpatterns
thatmostaccuratelypredictlongtermneurodevelopmental
sequelae.11
Duetothehighriskofneurodevelopmentalimpairment
in extremely preterm infants, methods toassess the risk
havebeen sought. The etiology ofpreterm braininjury is
assumedtobemultifactorial,includingeventsinthe
peri-partum period as well as acquired white matter injury,
inflammation, and infections that may occur during
hos-pitalization.Usefulassessmentshaveincluded clinicalrisk
scores,neuroimaging, andearly brainfunction.As
neona-talbrainfunctioncanbereadilyassessedusingaEEG,ithas
beenintenselyinvestigatedasaprognostictool.Background
pattern, SWC, and seizures have been used to
prognosti-catewithseveral studies showinga goodcorrelation with
outcome.12,13Ascoringsystemtoobjectivelyassess
devel-opmentalmaturationatincreasinggestationalandpostnatal
ageswasdevelopedbyBurdjalovetal.14 Theirscoring
sys-temusesmeasuresofcontinuity,presenceofcyclicchanges,
degree of voltage amplitude depression, and bandwidth.
The cycling score appeared to have the highest
correla-tionwithpost-conceptualageandwasfelttobethesingle
bestsignofcerebralmaturity.Arecentmeta-analysisofthe
prognosticaccuracy of early (within 7 days of life) aEEG
or EEG to predict neurodevelopmental outcome at 1---10
yearsofageconcludedthatthesemeasureshavethe
poten-tialtopredictlaterneurodevelopmentaloutcome;however,
there was substantial heterogeneity among studies with
differing prognostic variables and outcomes.15 They
con-cludedthathigh-qualitystudiesareneededtoconfirmthese
findings.
aEEGhasseveraladvantagesovercontinuousEEG(cEEG)
butit does notreplaceitasthegold standardfor seizure
diagnosisorfortheevaluationoftheEEGbackgroundbrain
activity. Due to the limited number of channels that are
recorded(usuallyleftandright parietal orcentral leads),
aEEGiseasytoapplywithouttheneedofanEEGtechnician.
Favorable characteristics of aEEG include the following:
aEEGisoftenavailableinclinicalsettingswherefull
conven-tionalEEGisnotreadilyavailable;aEEG’sleadapplicationis
easytolearnandisnotatime-consumingprocedure;aEEG
can be used to monitor for long periods of timewithout
burdening neurophysiologists, aEEG recording devices are
easytouseandhaveasmallbedsidefootprint;aEEGcanbe
incorporatedintothesoftwareofconventionalEEGdevices,
allowingforsimultaneousrecordinganddisplayoftheaEEG
compressedtraceaswellasthefullvideo-EEG;aEEGiseasy
tointerpretwithapatternbasedclassificationsystemthat
parallelstheclassificationofconventionalEEG,butdoesnot
require extensive training in neurophysiology; and finally,
theprognosticabilityofaEEGmaybesuperiortomore
sub-jectiveevaluationssuchastheneonatalneurologicexam.
aEEGdoeshaveimportantlimitationsespeciallywhenbeing
usedtodiagnoseseizures.Duetothemannerinwhichthe
signalisrecordedandhowthecompressedaEEGtraceis
cre-ated,someseizurescanbemissed.First,aEEGonlyrecords
EEGsignalfromalimitednumberofchannels/regionsofthe
brain.Seizuresthatariseinareasawayfromtherecording
leads may not be capturedand therefore can be missed.
Inaddition,seizuresthatarebrief(<30s)orlowamplitude
maybedifficulttoidentifyonthecompressedtrace.Using
onlythecompressedaEEGtracetoidentifyseizuresresults
in low sensitivity and specificity for seizure recognition;
therefore, both thecompressedand rawtraces shouldbe
evaluated.16NeweraEEGdeviceshaveincorporatedseizure
detectionsoftwaretoassistbedsidecliniciansinidentifying
seizures.BasedonasurveyofUSneonatologistsperformed
in2012,55%ofneonatologistsreportedusingaEEGintheir
practice.HIEandsuspectedseizureswerethemostcommon
indicationsforuse,andaEEGwasprimarily interpretedby
neonatologists(87%).17 Pediatricneurologists acknowledge
theimportantroleaEEGplaysintheNICUtoidentifyseizures
andassessbrainfunction.Itlessensthedemandfor
conven-tionalvideoEEG,whichismorecostly,requiringspecialized
EEGtechnicianstoperformtherecordingsand
neurophysi-ologistsforinterpretation.Glassetal.encouragepediatric
neurologiststolearnaEEGinterpretationinordertoimprove
communicationandcarecoordinationatthebedside.18
Brain-focused care is now possible in NICUs equipped
with neuromonitoring techniques such asaEEG and NIRS.
The inevitable and critical question is whether the use
of these neuromonitoring techniques will improve
long-term neurodevelopmental outcomes. The wider use of
aEEG has the potential toincrease seizureidentification,
decrease seizure burden, and potentially minimize
expo-suretoanticonvulsantmedicationsbyaccuratelyidentifying
patientswithelectrographicseizures.Tworecent
investiga-tions have dealt withthe question of whether aggressive
treatment of neonatalseizuresdecreases braininjury.19,20
Van Rooij et al. found a significant relationship between
seizure duration and MRI severity scores, supporting the
assumption that seizures worsenexisting braininjury.19 A
Brain-focusedcareintheneonatalintensivecareunit:thetimehascome 441
for electrographic seizures to those treated for clinical
seizures alone; seizure burden, MRI findings, and
neu-rodevelopmental outcome were improved in the cohort
with treatment of electrographic seizures.20 We eagerly
anticipateadditionalclinicalstudiesusingneuromonitoring
techniquessuchasaEEGandNIRSthatwillprovideusthe
evidence onhowthese technologiesmay bebest usedto
optimizeintensivecarepracticesandlessenbraininjury.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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