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Managementoffebrileseizures

SecondLevelCarereferstohospitals,atacommunityordistrictlevel,providing24houraccessandstaffedbydoctorsandnurseswithexpertiseinresuscitation.

ProfessionalorganizationsofItaly,UnitedKingdomandUnitedStatesofAmericahaveprovidedguidelinesforvariousaspectsofdiagnosisandmanagementoffebrileseizures(SummarizedinTable1).Theequipment,drugsanddiagnosticteststhatshouldbeavailableforthemanagementoffebrileseizuresineachoftheselevelsaresummarizedinTable2.However,theseelementsarenotavailableinmanyhealthcarefacilitiesinresourcepoorcountries.Forexample,inasurveyoffirstlevelcarefacilitiesinthreecountriesinAfrica,only74%hadabenzodiazepineavailable(Simoesetal,2003).

Table1:RecommendationsbyProfessionalOrganizationsonManagementofFebrileSeizures

AmericanAcademyofPaediatrics(AAP,

1996)

JointWorkingGroupoftheResearch

UnitoftheRoyalCollegeofPhysicians

andBritishPaediatricAssociation,

1991

ItalianLeagueAgainstEpilepsy

(Capovillaetal,2009)

Admissiontohospital Notstated 1. Achildagedlessthan18months

2. Acomplexseizure,i.e,onelasting

longerthan20minutes,with

focalfeatures,repeatedinthe

sameepisodeofillnessorwith

incompleterecoveryafterone

hour

3. Earlyreviewbyadoctorathome

notpossible

4. Homecircumstancesinadequate,

ormorethanusualparental

anxiety,orparents'inabilityto

1. Achildagedlessthan18months

2. ComplexFS

3. FSinchildrenwithoutareliablefamiliar

context

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cope

Investigations

Ina

healthy

child

with

a

first

simple

febrileseizure:

1. Alumbarpuncture(LP)shouldbe

a) stronglyconsideredinachild

youngerthan12months;

b)

shouldbe

considered

in

children

between12and18months;

c) performedinchildrenolder

than18months,ontheclinical

suspicionofmeningitis.

2.

Bloodtests

are

not

required

3. Electroencephalography(EEG)isnot

required

4. Neuroimagingisnotrequired

1.

SimpleFS

none

2. ALPshouldbeperformedif:

Clinicalsignsofmeningism;

afteracomplexconvulsion;

childis

unduly

drowsy

or

irritable

orsystemicallyill;

ifthechildisagedlessthan18

months(probably)andalmost

certainlyifthechildisagedless

than12months.

1.

Simplefebrile

Seizures

in

a

child

>

18

monthsNone

2. SimpleFSinachild


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3min

1. Diazepam0.5mg/kgIV

2.

Canrepeatafter10minsifseizurenot

stopped

Prophylaxisagainst

recurrences

Notstated Notrecommended,although

occasionallydrug

prophylaxis

may

be

usedforachildwhohasfrequent

recurrences.

1. IfSimpleFSnone

2. Considerprophylaxisin

a.

RecurrentFSwithreliableparents

b. >3FSin6months

c. >4FSin1yr

Education Notstated 1. Anexplanationofthenatureof

FS,includinginformationabout

theprevalenceandprognosis

2. Instructionsaboutthe

managementoffever,the

management

of

a

seizure,

and

the

useofrectaldiazepam(see

above)

3. Reassurance.

1. DescribedetailsofFS

2. Instructionsforfevercontrol

3.

Discussprophylacticdrugs

4. Educationonhowtomanagepossible

recurrences:

a. Remaincalm,nopanic;

b.

Loosenthechildsclothing,especially

aroundtheneck;

c. Ifthechildisunconscious,placethechild

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inthelateraldecubitusposition,toavoid

inhalationofsalivaorvomitus;

d. Donotforceopeningofthemouth;

e. Observethetypeanddurationofthe

seizure;

f. Donotgiveanydrugsorfluidsorally;

g.

Administerrectal

diazepam

0.5

mg/kg,

in

caseofprolongedseizurelastingover23

min.

h.

Inanyevent,contactthefamily

paediatrician,orotherpractitioner;

i.

A

medical

intervention

is

necessary

in

the

followingcases:

Seizuresofaduration>10minornot

remittingaftertreatment

Recurrentseizures,

Focalseizures,

Presenceofprolongedconsciousness

disorder,and/orpostictalpalsy

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Table2:EquipmentandSuppliesfortheDiagnosisandManagementofFebrileSeizures

ResourceRich

Countries

Resource

Poor

countries

FirstLevel Secondlevel FirstLevel Secondlevel

Equipment Syringes

Needles

Weighingscales

Refrigerator

Thermometer

()

Oxygen Oxygencylinder

Oxygenconcentrator

()

Diagnosticfacilities Bloodslide

Fullbloodcount

Bloodglucose

Electrolytes

Bloodculture

UrineMicroscopy

()

()

()

()

6


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andculture

CSFMicroscopy

andculture

CTscan

MRIscan

()

()

(

)

X

X

Drugs

Benzodiazepines

Phenytoin

Phenobarbital

()

Theparents'attitudestofebrileseizuresvaryconsiderablyaroundtheworld.ThismayeffectthepresentationandmanagementofFSatprimaryand

secondarycarefacilities.InanIndiancity59%ofparentsdidnotrecognizeaconvulsionand91%didnotperformanyinterventionsbeforeattending

hospital(Parmaretal,2001),whilstinTurkeysomeparentsadministeredrectalDiazepam(Yilmazetal,2008).Provisionofleafletswithwritteninstruction

toBritishparentsdidnotappeartosignificantlyimprovetheirknowledgeorreduceanxietyaboutFS(Pauletal,2007).

Population/Intervention(s)/Comparison/Outcome(s)(PICO)

Population: Childrenwithfebrileseizures

Interventions:

Diagnostictests

such

as

lumbar

puncture,

blood

tests

(for

malaria

parasite,

counts,

culture),

EEG

and

neuroimaging

Comparison: NotapplicableOutcomes: Appropriatediagnosisandimprovedmanagement

Searchstrategy

ThesearchstrategywasconductedwiththesearchtermsoutlinedinTable3.

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Table3:

Search

Strategy

for

the

Management

of

Febrile

Seizures

in

First

and

Secondary

Level

facilities

Breakdownofsearchremitprovided:

Mainquestion:Can(1)febrileseizure(2)bemanagedat(3)firstand(4)secondlevelcare?

AdditionalvariationoftermsforBooleansearch:((febrileseizures)OR(febrileconvulsions))AND((firstlevel)OR(primaryhealthcare)OR(primary

care))AND((secondarylevelcare)OR(secondaryhealthcare)OR(secondarycare))

Database BooleanSearch Limits Total

Pubmed ((febrileseizures)OR(febrileconvulsions))AND

((managed)OR(management)OR(case

management)OR(riskmanagement)OR(patient

caremanagement))AND((firstlevelcare)OR

(primaryhealthcare)OR(primaryhealthcare)OR

(primarycare))AND((secondarylevelcare)OR

(secondaryhealthcare)OR(secondarylevelhealth

care)or(secondarycare))

Humans,fromunspecifiedanduntil

2009/01/3.Pleasenote,searchwas

basedonpartialBoolean:

((febrileseizures)

OR

(febrile

convulsions))

CompleteBoolean=3

PartialBoolean=2875

Cochrane ((febrileseizures)OR(febrileconvulsions))AND

((managed)OR

(management)

OR

(case






Unabletospecifylimits 45

8


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PsychInfo Noresultsevenfor'febrileseizures'or'febrileconvulsions'

0

MedlinePlus ((febrileseizures)OR(febrileconvulsions))AND









WHOAfricaIndex

Medicus

Unabletospecifylimits.Noresultseven

for'febrile

seizures'

or

'febrile

convulsions'

0

WHOEastern

Mediterranean

Unabletospecifylimits.Databaseused

wasEMRO/IMEMRtoavoiddefaulting

toVirtualHealthLibraryorusingsub

database,EMCAT.Unabletoperform

Booleansearch

((febrile

seizures)

OR

(febrileconvulsions))

'febrileseizures'=71

'febrileconvulsions'=31

WHOEurope ((febrileseizures)OR(febrileconvulsions))AND




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(primarycare))

AND

((secondary

level

care)

OR



WHOLatinAmerican&

Caribbean

((febrileseizures)OR(febrileconvulsions))AND



caremanagement))

Unabletospecifylimits.Databasesearch

defaultedtoVirtualHealthLibrary.Had

tospecifyLILACS.Booleanprovidedno

resultsbeyondthispoint

5

WHOSouthEastAsia ((febrileseizures)OR(febrileconvulsions))AND




(primaryhealthcare)

OR

(primary

health

care)

OR





WHOWesternPacific Unabletospecifylimits.Boolean

providedonly6resultsfor((febrile

seizures)AND

(febrile

convulsions)).

Therewerenoresultsfor(febrile

convulsions)

(febrileseizures)=67

Articleschosenoutof

alldatabasesearches

Total

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performed

Pubmed

282

Totalaccessed

Pubmed 230

INCLUSIONANDEXCLUSIONCRITERIA

Studiesdescribingthediagnosisandmanagementofchildrenwithfebrileseizureswerereviewed,andsomestudiesthatreportedchildrenpresentingto

thirdlevelcareonlywereincludediftheyprovidedinformationthatwashelpfultothemanagementofFSinfirstandsecondlevelcare.

Studiesdescribingonlynonfebrileseizuresandepilepsywereexcluded.

Narrativedescription

of

the

studies

that

went

into

the

analysis

Thesearchoftheliteraturedidnotrevealanyrandomizedcontroltrialsofinterventionsthatspecificallyexaminedthemanagementoffebrileseizuresin

theprimaryorsecondarycaresettings

Diagnosis

of

Febrile

seizures

Febrileseizureissyndromebaseduponclinicalhistoryandobservation,andshouldbedifferentiatedfromrigours,febriledelirium,febrilesyncopeor

breathholdingattacks.Therearenofeaturesdetectedbyphysicalexamthatconfirmthediagnosis,althoughexaminationmaydetectfeaturesofan

underlyingcauseofFSe.g.upperrespiratorytractinfectionoridentifyothersyndromesthatcauseseizurese.g.neurofibromatosis.Febrileseizurescanbe

causedbyavarietyofinfections,andthediagnosticproceduresareaimedatidentifyingtheunderlyingcausesandexcludingseriousintracranialinfections

suchasacutebacterialmeningitisorviralencephalitisthatrequirespecificinterventions.Itisestimatedthatacutebacterialmeningitisoccursin27%of

childrenwhopresentwithseizuresassociatedwithfever(Fetveit,2008).Mostofthisdatawasgatheredbeforetheintroductionofvaccinesagainstthe

maincausesofbacterialmeningitisandisderivedfromresourcerichcountries.

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c) Complexfebrileseizures

The

literature

suggests

that

complex

febrile

convulsions

(defined

above)

are

predictive

of

CNS

infection

(Green

et

al,

1993;

Joffe

et

al,

1983;

Offringa

et

al,

1992a;OffringaandMoyer,2001).Theriskofbacterialmeningitisinchildrenpresentingwithfeverandseizureisabout3%(McIntyreetal,1990)andwith

acomplexseizureisabout9%.

AfterthefirstDelphirounditwasagreedthatchildrenwithcomplexseizuresshouldbeadmittedtohospital.Afteradmissionitwasrecommendedthata

childpresentingwithacomplexfebrileseizure(definedabove)withnoclinicalsignsofmeningitisshouldbeobservedcloselyandreviewedwithintwo

hoursbyapaediatricianofatleastRegistrar/ResidentleveltodecideonneedforLP.

Referralfrom

First

level

care

SeizuresareoneofthedangersignsthattheWorldHealthOrganizationsIntegratedManagementofChildhoodIllness(IMCI)suggeststhatthechildshould

bereferredtoasecondlevelfacility(WHO,2005).Inonestudyof151childrenaged2monthsto5yearswhopresentedwithconvulsionstofirstlevelcare

facilitiesinthreecountriesinAfrica,itwassuggestedthatonly12%neededtoreferredtoasecondlevelfacility,sincetheyhadothersignssuchaslethargy,

impairedconsciousnessand/orunabletodrink(Simoesetal,2003). Therehavebeennootherstudiesthathaveaddressedthisquestionwithinthissetting.

Education

ExplanationandeducationaboutFSoftheparentsand/orguardiansisanimportantcomponentofthemanagementofFSatalllevels.Thisincludes

explanationaboutthecausesofFS,thediagnosticproceduresthatmaybeperformedtoexcludeseriousinfectionsandtheoutcomeoftheFS.Further

adviceaboutpreventingrecurrenceandinitiatingtreatmentmaybehelpfulinappropriatecircumstances.

Methodologicallimitations

Mostof

the

studies

did

not

clearly

state

the

facilities

available

for

the

diagnosis

and

management

of

FS

in

their

reports.

Directness(intermsofpopulation,outcome,interventionsandcomparison)

Mostofthestudiesidentifiedhadbeenconductedintertiaryemergencydepartments,andnonecomprehensivelyexaminedthediagnosisand

managementofFSinfirstorsecondlevelcare.TherewerenoauditsofthemanagementofFSinprimarycaresettings.

NarrativeConclusion

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NopublishedstudieswereidentifiedthatspecificallyaddressedthequestionastowhetherFScouldbemanagedatfirstlevelcareorsecondarylevelcare.

HoweverthestudiesthatexaminedthecomponentsofthemanagementofFS(particularlythedrugmanagement)atthesefacilitiesandconsensus

statementsfrom

Western

experts

were

identified,

suggest

that

simple

FS

(particularly

if

it

is

the

first

FS)

may

be

managed

a

first

level

facilities,

although

thosechildrenwithfeaturesofcomplexFSmayneedtobereferredtosecondlevelcare.Investigationsrarelyinfluencemanagement,exceptthatthe

exclusionofcentralnervoussysteminfectionsisimportant,particularlyinchildrenlessthan18monthsold.

ReferenceList

AmericanAcademyofPaediatrics(AAP)(1996).Practiceparameter:theneurodiagnosticevaluationofthechildwithafirstsimplefebrileseizure.

Provisional

Committee

on

Quality

Improvement,

Subcommittee

on

Febrile

Seizures.

Paediatrics,

97:769

72.

ArmonKStephensonT,MacFaulRetal(2003).Anevidenceandconsensusbasedguidelineforthemanagementofachildafteraseizure.Emergency

MedicineJournal, 20:1320.

BergATetal(1992).Classificationofcomplexfeaturesoffebrileseizures:interrateragreement.Epilepsia,33:6616.

CapovillaGetal(2009).Recommendationsforthemanagementof"febrileseizures":AdHocTaskForceofLICEGuidelinesCommission.Epilepsia,50(Suppl

1):26.

ChamberlainJM,GormanRL(1988).Occultbacteraemiainchildrenwithsimplefebrileseizures.AmercianJournalofDiseasesofChildren,142:10736.

FetveitA(2008).Assessmentoffebrileseizuresinchildren.EuropeanJournalofPaediatrics, 167:1727.

GarveyM.Aetal(1998).Emergencybraincomputedtomographyinchildrenwithseizures:whoismostlikelytobenefit?JournalofPaediatrics,133:6649.

Gerber

MA,

Berliner

BC

(1981).

The

child

with

a

'simple'

febrile

seizure.

Appropriate

diagnostic

evaluation.

Amercian

Journal

of

Diseases

of

Children,

135:4313.

GreenSMetal(1993).Canseizuresbethesolemanifestationofmeningitisinfebrilechildren?Paediatrics,92:52734.

HampersLCetal(2006).Febrileseizure:measuringadherencetoAAPguidelinesamongcommunityEDphysicians.PaediatricEmergencyCare,22:4659.

HampersLCetal(2000).Settingbasedpracticevariationinthemanagementofsimplefebrileseizure.AcademicEmergencyMedicine, 7:217.

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HesdorfferDC,ChanS,TianH(2008).AreMRIdetectedbrainabnormalitiesassociatedwithfebrileseizuretype?Epilepsia, 49:76571.

International

League

Against

Epilepsy

(ILAE)

(1993).

Guidelines

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Epidemiologic

studies

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Epilepsy.

Epilepsia,

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6.

JoffeA,McCormickM,DeAngelisC(1983).Whichchildrenwithfebrileseizuresneedlumbarpuncture?Adecisionanalysisapproach.AmercianJournalof

DiseasesofChildren,137:11536.

JoshiCetal.(2005).DoclinicalvariablespredictanabnormalEEGinpatientswithcomplexfebrileseizures?Seizure,14:429434.

Kimia AAetal(2009).Utilityoflumbarpunctureforfirstsimplefebrileseizureamongchildren6to18monthsofage.Paediatrics,123:612.

KuturecMetal(1997).Febrileseizures:istheEEGausefulpredictorofrecurrences?ClinicalPaediatrics(Philadelphia),36:3136.

LahatEetal(2000).Comparisonofintranasalmidazolamwithintravenousdiazepamfortreatingfebrileseizuresinchildren:prospectiverandomizedstudy.

BritishMedicalJournal,321:8386.

MaytalJetal (2000).ThevalueofearlypostictalEEGinchildrenwithcomplexfebrileseizures.Epilepsia, 41:21921.

McIntyre

J

et

al

(2005).

Safety

and

efficacy

of

buccal

midazolam

versus

rectal

diazepam

for

emergency

treatment

of

seizures

in

children:

a

randomized

controlledtrial.Lancet,366:20510.

McIntyrePB,GraySV,VanceJC(1990).Unsuspectedbacterialinfectionsinfebrileconvulsions.MedicalJournalofAustralia,152:1836.

NatsumeJetal(2007).Hippocampalvolumesanddiffusionweightedimagefindingsinchildrenwithprolongedfebrileseizures.ActaNeurologica

Scandinavica,115:258.

OffringaM

et

al

(1992a).

Seizures

and

fever:

can

we

rule

out

meningitis

on

clinical

grounds

alone?

Clinical

Paediatrics

(Philadelphia),

31:514

22.

OffringaMetal(1992b).Seizurerecurrenceafterafirstfebrileseizure:amultivariateapproach.DevelopmentalMedicine&ChildNeurology,34:1524.

OffringaM,MoyerVA(2001).Evidencebasedpaediatrics:Evidencebasedmanagementofseizuresassociatedwithfever.BritishMedicalJournal,323:1111

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OwusuOforiAetal(2004).RoutinelumbarpunctureinchildrenwithfebrileseizuresinGhana:shoulditcontinue?InternationalJournalofInfectious

Diseases, 8:35361.

ParmarRC,SahuDR, BavdekarSB(2001).Knowledge,attitudeandpracticesofparentsofchildrenwithfebrileconvulsion.JournalofPostgraduate

Medicine, 47:1923.

PaulFetal(2007).Thequalityofwritteninformationforparentsregardingthemanagementofafebrileconvulsion:arandomizedcontrolledtrial.Journal

ofClinical Nursing,16:230822.

JointWorkingGroupoftheResearchUnitoftheRoyalCollegeofPhysiciansandtheBritishPaediatricAssociation(1991).Guidelinesforthemanagementof

convulsionswith

fever.

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RutterN,SmalesORC(1977).Roleofroutineinvestigationsinchildrenpresentingwiththeirfirstfebrileconvulsion.ArchivesofDiseaseinChildhood,

52:18891.

SeltzLB,CohenE,WeinsteinM(2009).Riskofbacterialorherpessimplexvirusmeningitis/encephalitisinchildrenwithcomplexfebrileseizures.Paediatric

EmergencyCare,25:4947.

ShakedOetal (2009).Simplefebrileseizures:aretheAAPguidelinesregardinglumbarpuncturebeingfollowed?PaediatricEmergencyCare,25:811.

ShivaF,HashemianHR(1998).Febrileseizures:clinicalcourseanddiagnosticevaluation.JournalofPakistanMedicalAssociation, 48:2767.

ShorvonS(1994).Statusepilepticus.Itsclinicalfeaturesandtreatmentinchildrenandadults.Cambridge:CambridgeUniversityPress.

SimoesEAetal (2003).ManagementofseverelyillchildrenatfirstlevelhealthfacilitiesinsubSaharanAfricawhenreferralisdifficult.BulletinofWorld

HealthOrganization,81:52231.

SofouKetal(2009).ManagementofProlongedSeizuresandStatusEpilepticusinChildhood:ASystematicReview.JournalofChildNeurology,24:91826.

StoresG(1991).WhendoesanEEGcontributetothemanagementoffebrileseizures?ArchivesofDiseasesinChildhood,66:5547.

TakanashiJetal(2006).DiffusionMRIabnormalitiesafterprolongedfebrileseizureswithencephalopathy.Neurology,66:13049.

18
http://www.uptodate.com/patients/content/abstract.do?topicKey=%7Ejrupuic1lKQHlRs&refNum=46http://www.uptodate.com/patients/content/abstract.do?topicKey=%7Ejrupuic1lKQHlRs&refNum=46http://www.uptodate.com/patients/content/abstract.do?topicKey=%7Ejrupuic1lKQHlRs&refNum=46http://www.uptodate.com/patients/content/abstract.do?topicKey=%7Ejrupuic1lKQHlRs&refNum=46


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TengDetal(2006).Riskofintracranialpathologicconditionsrequiringemergencyinterventionafterafirstcomplexfebrileseizureepisodeamongchildren.

Paediatrics, 117:3048.

WorldHealthOrganization(2005).HospitalCareforChildren.Geneva,Switzerland,WorldHealthOrganization.

YilmazDetal(2008).Attitudesofparentsandphysicianstowardfebrileseizures.ClinicalPaediatrics(Philadelphia),47:85660.

YucelOetal(2004).RoleofearlyEEGandneuroimagingindeterminationofprognosisinchildrenwithcomplexfebrileseizure.Paediatrics International,

46:4637.

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Addressingparentalanxietyformsakeypartofthemanagementofsimplefebrileseizures,asparents'(unspoken)worrywithafirstseizureisthattheir

childmighthavedied.However,thereislittleinthemedicalliteratureaboutthisaspectofeducationandreassuranceinmanagementofsimplefebrile

seizures.

Population/Intervention(s)/Comparison/Outcome(s)(PICO)

Population: childrenwithfebrileseizures

Interventions: intermittentantipyretictreatment(paracetamol,ibuprofen,physicalmethods)

intermittentanticonvulsant

treatment

(intermittent

diazepam)

continuousanticonvulsanttreatment(phenobarbital,valproate)

Comparison: notreatment

Outcomes: preventionofrecurrenceoffebrileseizure

epilepsy

adverseeffectsofdrugs

Listofthesystematicreviewsidentifiedbythesearchprocess

SEARCHSTRATEGY:Cochranedatabase,NICEguidelines,SIGNguidelines,BMJclinicalevidence,PUBMEDsearchforreviews,clinicalqueries(term"simple

febrileseizure")

INCLUDEDINGRADETABLESORFOOTNOTES

ThesystematicreviewsandRCTsincludedinthePICOtablearebasedontheClinicalEvidence(Mewasingh,2008).

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PICOtable(onerowforeachGRADEtable)

Serial

no. Intervention/Comparison

Outcomes

Systematic

reviews

identified

Systematic

review/evidence

used

for

GRADE

and

explanationIntermittentantipyretictreatment1 Physicalmethodsoftemperature

reductionvs.antipyretic

drugs/placebo

NosystematicrevieworRCTidentified;

2 Antipyreticdrugsvs.placebo Preventionofrecurrenceof

febrileseizures

Adverseeffects

ElRadhi&Barry,2003

Meremikwu,2007 Meremikwu,2007,Analysis1.2,comparison1Intermittentanticonvulsants

3 Intermittentdiazepamvs.placeboornotreatment

Preventionofrecurrenceoffebrileseizures

Adverseeffects

Riskofsubsequentepilepsy

Masukoetal,2003;Temkin,2001;Pavlidouetal;2006

Notreportedintheabove

tworeviewsbutdata

providedbysomeofthe

included studies;

Pavlidouetal,2006

Nosystematicreview;Knudsenetal,1996(RCT)

ReviewbyMasukoetalismorerecent,thetworeviewsidentifiedthreeoftheRCTs,searchedandincludedPortugueseandSpanishstudies,althoughoneRCTisreporteddifferentlyintworeviews*

Toprovidethenarrativeinformation(notGRADEd)

Singlestudy(Knudsenetal,1996)

4 Intermittentclobazamvs.placeboornotreatment


Nosystematicreview,2RCTsreportedinBMJclinicalevidence(Mewasingh2008)

Roseetal,2005;Bajajetal,2005

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Adverseeffects Sameasabove

5

Intermittent

vs.

continuous

anticonvulsant No

systematic

review

or

RCT

identified

Continuousanticonvulsants

6 ContinuousPhenobarbitalvs.placeboornotreatment


Adverseeffects


Masukoetal,2003;Temkin,2001

Notreportedinabovetwo

reviewsbut

data

provided

by

someoftheincludedstudies;

Camfieldetal,1979

Nosystematicreview;Wolf&Forsythe,1989(RCT)

Temkin2001 8RCTs(all6thatareincludedinMasuko2003),bothreviewsfoundheterogeneityamongtrials.

7 Continuousvalproatevs.placebo

orno

treatment

Preventionof

recurrenceof

febrileseizures

Adverseeffects


Temkin,2001

Notreportedintheabove

review

NosystematicrevieworRCT

8 ContinuousPhenobarbitalvs.continuousvalproate


Adverseeffects

Masukoetal,2003

NoinformationfromtherevieworincludedRCT

OneRCTfromthesystematicreview(Mamelleetal,1984)

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M f f b il i


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TheAmericanAcademyofPaediatrics,1999, basedontheirsystematicreview(nometaanalysisdone), reportedthatonly4%ofchildrentakingvalproic

acid,asopposedto35%ofcontrolsubjects,hadasubsequentfebrileseizure.Therefore,valproicacidseemstobeatleastaseffectiveinpreventing

recurrentsimple

febrile

seizures

as

phenobarbital

and

significantly

more

effective

than

placebo.

They

include

valproate

vs.

phenobarbital

and/or

placebo

trials.

GRADEtables:

Table1

Author(s):DuaT,HyunhN,BellG

Date:2009

08

12

Question:ShouldPhysicalmethodsoftemperaturereductionvs.Antipyreticdrugsbeusedinchildrenwithsimplefebrileseizures?Settings:

Bibliography:MewasinghLD(2008).Febrileseizures.ClinicalEvidence,(Online).May22;2008.pii:0324.

Summaryoffindings

Qualityassessment

Noofpatients Effect

Noof

studies

Design Limitations

Inconsistency

Indirectness Imprecision Other

considerations Physical

methods

of

temperature

reduction

Antipyretic

drugs Relative

(95%CI) Absolute

Quality

Importance

recurrenceoffebrileseizure notreported

0 none 0/0(0%) 0/0(0%) CRITICAL

Table2

Author(s):DuaT,HyunhN,BellG

Date:20090812

Question:ShouldAntipyreticdrugsvs.placebobeusedinchildrenwithsimplefebrileseizures?

Settings:

Bibliography:ElRadhiAS,BarryW(2003).Doantipyreticspreventfebrileconvulsions?ArchivesofDiseasesinChildhood,88:6412;

MeremikwuM,OyoItaA(2002).Paracetamolfortreatingfeverinchildren.CochraneDatabaseSystematicReviews,(2):CD003676.

28

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Summaryoffindings

Qualityassessment

Noofpatients Effect

Noof

studiesDesign LimitationsInconsistency Indirectness Imprecision

Other

considerations

Antipyretic

drugsplacebo

Relative

(95%CI)Absolute

Quality

Importance

Recurrenceoffebrileseizure

45/174

(25.9%)

13moreper1000(from67fewer

to129

more)

2 randomized

trials

serious1 noserious

inconsistency

serious2 noserious

imprecision

none

45/166(27.1%)

0%

RR1.05(0.74to

1.5)0moreper1000(from0fewerto

0more)

LOWCRITICAL

adverseeffects

4/124(3.2%) 27moreper1000(from11fewer

to135more)

33 randomized

trials

serious4 noserious

inconsistency

serious5 serious6 none

9/130(6.9%)

0%

RR1.84(0.65to

5.18)0moreper1000(from0fewerto

0more)

CRITICAL

1the2includedstudiesdoubleblindplacebocontrolledRCT;dropoutsnotdescribed;pooledanalysisdonebyself;BMJclinicalevidencedescribesthesystematicreviewtohaveweakmethods(inadequatesearch

methodsdifficulttoreplicate,noinclusion/exclusioncriteria);howevernoadditionalRCTidentifiedbyBMJclinicalevidence.2Noexplanationwasprovided.

3Meremikwu&OyoIta,2002,Cochranereview;analysis1.2,comparison1.

4Thesystematicreviewonantipyretic(bothparacetamolandibuprofen)vs.placeboinsimplefebrileseizuresdonotgiveinformationonadverseeffects.Thissystematicreviewcomparesparacetamolvs.placeboin

children

with

fever.

595%CI0.65 5.18(crossing1andupperCImorethan2).

6onestudyusedibuprofenandotherparacetamol.

Table3

Author(s):TarunDua,NellyHuynh,GailBell

Date:20090813

29


30/44


31/44


32/44



33/44

g

5Samplesize168.

6notreportedinotherincludedstudies.

7Thilothammaletal,1993:Adverseeffectsnecessitatingwithdrawal:3/60(5%)PBtreatedchildrenhadintolerableadverseeffects(definedaseffectspersistentforlongerthan1month),includinghyperkinetic

behaviour,extreme

irritability,

fussiness,

aggressiveness,

all

of

whom

withdrew

from

the

study

owing

to

the

adverse

effects.

1/30

(3.3%)

of

children

taking

placebo

withdrew

for

unknown

reasons.

Camfield

et

al,

1980 4/39(10%)inbothgroupswithdrewbecauseofintolerableadverseeffects.8Baconetal,1981;Wolfetal,1978.

9Wolfetal,1989notplacebocontrolled,dropoutsnotknown.

10Isquare65%.

11Farwelletal,1990.

12singlestudy.

13Camfieldetal,1979(notincludedinsystematicreview,additionalstudy) ChildrentakingPBhadlowerscoresonmemoryconcentrationitemsontheStanfordBinetIntelligencescaleat8 to12monthfollowup

comparedwithchildrentakingplacebo,althoughthedifferencebetweengroupswasnotsignificant(absolutenumbersnotreported;P=0.07).14

randomized,outcomeassessmentanddropoutNK,tocheckoriginalstudy.15

includesbothsimpleandcomplexfebrileseizure.16

95%CIverywideandlowerconfidencelimitcrossesariskof2.

Table6

Author(s):TarunDua,NellyHuynh,GailBell

Date:20090814

Question:ShouldContinuousvalproatevs.placebobeusedinchildrenwithsimplefebrileseizures?

Settings:

Bibliography:TemkinNR(2001).Antiepileptogenesisandseizurepreventiontrialswithantiepilepticdrugs:metaanalysisofcontrolledtrials.Epilepsia,42:51524.

SummaryoffindingsQualityassessment

Noofpatients Effect

Noof

studiesDesign Limitations Inconsistency Indirectness Imprecision

Other

considerations

Continuous

valproateplacebo

Relative

(95%CI)Absolute

QualityImportance

Recurrenceof

febrile

seizure

34/114(29.8%)

78fewerper1000(from227fewerto367more)

3 randomizedtrials

veryserious

1,2serious

3noseriousindirectness

serious4

none

29/102(28.4%)

0%

RR0.74(0.24to2.23) 0fewerper1000(from0fewerto

0more)

VERYLOW

CRITICAL

adverseeffects notmeasured5

0 none 0/0(0%) 0/0(0%) CRITICAL

riskofsubsequentepilepsy notreported

33



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0 none 0/0(0%) 0/0(0%) CRITICAL12/3studiesnotplacebocontrolled.

2AmericanAcademyofPaediatrics,1999practiceparametersystematicreviewincludedvalproatevs.phenobarbital/vs.placebostudies.Oneoftheincludedstudiesinthatreview(WallaceandSmith,1980)isnot

includedin

Temkin,

2001

systematic

review.

Reason

for

exclusion

not

clear.

3Isquarenotprovided,howevertestsforstatisticalheterogeneitywasfoundsignificant.Visualinvestigationofforestplotalsosuggestsheterogeneity.

495%CIcrossing1andupperCImorethan2.

5Thereareknownrare,seriousadverseeffectsofsodiumvalproateincludehepatotoxicityandhaematologicaltoxicity.Althoughvalproatehepatotoxicitymaybedosedependent,itcan,morerarely,bean

idiosyncraticphenomenonwhichmeansthatitisoftenirreversibleanddifficulttopredictonthebasisoflaboratorymonitoring.Blooddisturbancescanalsobedosedependent,withdirectbonemarrow

suppressionleadingtoaplasticanaemiaorperipheralcytopeniaaffectingoneormorecelllines,orevenfatalbonemarrowfailure.

Table7

Author(s):Tarun

Dua,

Nelly

Huynh,

Gail

Bell

Date:20090814

Question:ShouldContinuousphenobarbitalvs.Continuousvalproatebeusedinchildrenwithsimplefebrileseizures?

Settings:

Bibliography:MasukoAHetal(2003).Intermittentdiazepamandcontinuousphenobarbitaltotreatrecurrenceoffebrileseizures:asystematicreviewwithmetaanalysis.ArquivosdeNeuroPsiquiatria,61:897901.

Epub2004Jan6.

Summaryoffindings

Qualityassessment

Noofpatients Effect

Noof

studiesDesign Limitations Inconsistency Indirectness Imprecision

Other

considerations

Continuous

phenobarbital

Continuous

valproate

Relative

(95%CI)Absolute

Quality

Importance

Recurrenceoffebrileseizure(followupmean23months)

4/21(19%)

145fewerper1000(from185

fewerto183more)

1 randomized

trials

noserious

limitations1noserious

inconsistency2serious2 very

serious3none

1/22(4.5%)

0%

RR0.24(0.03

to1.96)0fewerper1000(from0

fewerto0more)

OOO

VERY

LOW

CRITICAL

adverseeffects notmeasured

34



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0 none 0/0(0%) 0/0(0%) CRITICAL4

riskofsubsequentepilepsy notmeasured

0 none 0/0(0%) 0/0(0%) CRITICAL

1checkdropoutrateandoutcomeassessmentfromtheoriginalpaper.

2singlestudy.

3samplesizelessthan100,95%CIwidewithnoeffectandappreciablebenefit.

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ArmonKetal(2003).Anevidenceandconsensusbasedguidelineforthemanagementofachildafteraseizure.EmergencyMedicalJournal,20:1320.

Autret

E

et

al

(1990).

Double

blind,

randomized

trial

of

diazepam

versus

placebo

for

prevention

of

recurrence

of

febrile

seizures.

Journal

of

Paediatrics,

117:4904.

BaconCJetal(1981).Behaviouraleffectsofphenobarbitoneandphenytoininsmallchildren.ArchivesofDiseaseinChildhood,56:836840.

BajajASetal(2005).Intermittentclobazaminfebrileseizures:anIndianexperience.JournalofPaediatricNeurology, 3:1923.

BergATetal(1992).Classificationofcomplexfeaturesoffebrileseizures:interrateragreement.Epilepsia,33:6616.

CamfieldSetal(1979).Sideeffectsofphenobarbitalintoddlers;behavioralandcognitiveaspects.JournalofPaediatrics,95:3615.

CapovillaGetal(2009).Recommendationsforthemanagementof"febrileseizures":AdHocTaskForceofLICEGuidelinesCommission.Epilepsia,50(Suppl1):26.

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ConsensusinMedicine(1980).Febrileseizures:longtermmanagementofchildrenwithfeverassociatedseizures.SummaryofanNIHconsensusstatement.BritishMedicalJournal,281:2779.

ElRadhi

AS,

Barry

W

(2003).

Do

antipyretics

prevent

febrile

convulsions?

Archives

of

Diseases

in

Childhood,

88:641

2.

FarwellJRetal(1990).Phenobarbitalforfebrileseizureseffectsonintelligenceandonseizurerecurrence.NewEnglandJournalofMedicine,322:3649.

GreenSMetal(1993).Canseizuresbethesolemanifestationofmeningitisinfebrilechildren?Paediatrics,92:527534.

InternationalLeagueAgainstEpilepsy(ILAE)(1993).GuidelinesforEpidemiologicstudiesonEpilepsy.Epilepsia,34:5926.

JoffeA,McCormickM,DeAngelisC(1983).Whichchildrenwithfebrileseizuresneedlumbarpuncture?Adecisionanalysisapproach.AmericanJournalofDiseasesofChildren, 137:11536.

JointWorkingGroupoftheResearchUnitoftheRoyalCollegeofPhysiciansandtheBritishPaediatricAssociation(1991).Guidelinesforthemanagementofconvulsionswithfever.BritishMedicalJournal, 303:6346.

KnudsenFU(1985).Recurrenceriskafterfirstfebrileseizureandeffectofshorttermdiazepamprophylaxis.ArchivesofDiseasesinChildhood,60:10459.

KnudsenFUetal(1996).Longtermoutcomeofprophylaxisforfebrileconvulsions.ArchivesofDiseasesinChildhood,74:138.

MamelleNetal(1984).Preventionofrecurrentfebrileconvulsionsarandomizedtherapeuticassay:sodiumvalproate,phenobarbitalandplacebo.Neuropediatrics,15:3742.

MasukoAHetal(2003).Intermittentdiazepamandcontinuousphenobarbitaltotreatrecurrenceoffebrileseizures:asystematicreviewwithmetaanalysis.ArquivosdeNeuroPsiquiatria,61:897901.Epub2004Jan6.

McIntyrePB,GraySV,VanceJC(1990).Unsuspectedbacterialinfectionsinfebrileconvulsions.MedicalJournalofAustralia,152:1836.

MeremikwuM,OyoItaA(2002).Paracetamolfortreatingfeverinchildren.CochraneDatabaseSystematicReviews,(2):CD003676.

MewasinghLD(2008).Febrileseizures.ClinicalEvidence,(Online).May22;2008.pii:0324.

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MosqueraCetal(1987).[Preventingtherecurrenceoffebrileseizures:intermittentpreventionwithrectaldiazepamcomparedwithcontinuoustreatmentwithsodiumvalproate].Analesespanolesdepaediatria,27:37981.

OffringaM

et

al

(1992).

Seizures

and

fever:

can

we

rule

out

meningitis

on

clinical

grounds

alone?

Clinical

Paediatrics

(Philadelphia),

31:514

522.

OffringaM,MoyerVA(2001).Evidencebasedpaediatrics:Evidencebasedmanagementofseizuresassociatedwithfever.BritishMedicalJournal,323:11114.

PavlidouE,TzitiridouM,PanteliadisC(2006).Effectivenessofintermittentdiazepamprophylaxisinfebrileseizures:longtermprospectivecontrolledstudy.JournalofChildhoodNeurology,21:103640.

Rose

W,

Kirubakaran

C,

Scott

JX

(2005).

Intermittent

clobazam

therapy

in

febrile

seizures.

Indian

Journal

of

Pediatrics,

72:31

3.

RosmanNPetal(1993).Acontrolledtrialofdiazepamadministeredduringfebrileillnessestopreventrecurrenceoffebrileseizures.NewEnglandJournalofMedicine,329:7984.

SadleirLG,SchefferIE(2007).Febrileseizures.BritishMedicalJournal,334:30711.

TemkinNR(2001).Antiepileptogenesisandseizurepreventiontrialswithantiepilepticdrugs:metaanalysisofcontrolledtrials.Epilepsia,42:51524.

ThilothammalNetal(1993).Roleofphenobarbitoneinpreventingrecurrenceoffebrileconvulsions.IndianPaediatrics,30:63742.

WallaceSJ,SmithJA(1980).Successfulprophylaxisagainstfebrileconvulsionswithvalproicacidorphenobarbitone.BritishMedicalJournal,280:3534.

WaruiruCMetal(1996).EpilepticseizuresandmalariainKenyanchildren.TransactionsoftheRoyalSocietyofTropicalMedicineandHygiene,90:1525.

WolfSM,ForsytheA(1978).Behaviourdisturbance,phenobarbital,andfebrileseizures.Paediatrics,61:72831.

WolfSM,ForsytheA(1989).Epilepsyandmentalretardationfollowingfebrileseizuresinchildhood.ActaPaediatricaScandinavica,78:2915.

Fromevidencetorecommendations

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Factor Explanation

Febrileseizures

are

defined

as

simple

if

they

are

generalized,

often

tonic

clonic,

self

limiting,

of

shortduration(15minutes),orhavefocal

features,oriftheyrecurwithin24hours(multipleseizures).

Althoughnodataonthisisavailableregardingthecapacityofnonspecialisthealthcareproviders

fromlowandmiddleincomecountries(LAMIC)healthcaresettings,thereareclinicalcriteriato

differentiatesimple

from

complex

febrile

seizure.

Insimplefebrileseizures,localstandardsfordiagnosisandmanagementoffevershouldbe

followed.

Intervention/Compar

ator

Recurrenceof

febrileseizure

Adverseeffects Riskofsubsequent

epilepsy

Physicalmethods

of

temperature

reductionvs.

antipyretic

drugs/placebo

Narrative

summaryof

theevidence

base

Antipyreticdrugsvs.

placebo

2RCTs,No

significanteffect

RR1.05(0.741.50)

Nodifference

Nosignificantdifference,

verywide

confidence

intervals

(Theevidenceis

inconclusiveandsoitis

notpossibletodetermine

38



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ifthereisaclinically

importantdifference)

Intermittentdiazepamvs.placebo

ornotreatment

4RCTs,OR0.6(0.4

0.9)favouring

activetreatment

Notreportedbyreview,

fromindividualstudies

associatedwithincreased

hyperactivity,lethargy,

irritability,difficultiesin

speech,activitylevelor

sleep

SingleRCT,no

significantdifference

RR0.9(0.0614.27)

(selfcalculation)

(verywideCI)

Intermittent

clobazamvs.placebo

ornotreatment

2RCTs,RR0.31

(0.180.55)(self

calculation)

favouringactive

treatment

Significantlyincreased

ataxiainonestudy

Intermittentvs.

continuous

anticonvulsant

Continuous

Phenobarbitalvs.

placeboorno

treatment

Statistically

significantdifferenceRR0.51

(0.320.82),

favouringactive

treatment

Adverseeffect

necessitatingwithdrawal

(maybesignificant

differenceinonestudy,

otherstudy nosignificant

difference)(RR1.13(0.36

3.48);negativeeffecton

Singlestudy,RR7.6

(0.9560.87)

no

difference,wideCI

39



40/44

behaviour((maybe

significantdifferencein

one

study,

other

study

no

significantdifference)1.95

(1.332.87);statistically

significantnegativeeffect

oncognition

Continuousvalproate

vs.placeboorno

treatment

Nosignificant

differenceRR0.74

(0.242.23)

Continuous

Phenobarbitalvs.

continuousvalproate

Nosignificant

difference

RR0.24(0.031.96)

InLAMICsettings,febrileseizurespresentingtothehealthfacilitiesareoftencomplex.Complex

febrileseizures(CFS)indicateentitieswithvariableetiology,semiology,andprognosis.Therefore,

treatmentdependsupontheetiologicandnosographicpicture.ACFSmayresultfromanacute

disorderoftheCNS(suchascerebralmalaria,bacterialmeningitis,encephalitis)orcouldbesimply

aprolongedfebrileseizure.Admissionisrecommendedforobservationbecauseofthewide

variabilityofconditionsunderlyingthisevent. Searchforunderlyingetiologyisrecommendedin

case

of

CFS.

The

risk

of

bacterial

meningitis

in

children

presenting

with

fever

and

seizure

is

about

3%andinacomplexseizureabout9%.Childrenwithfollowingfeatures atleast3daysofillness,

seenbyGPinprevious24hours,drowsinessathome,vomitingathome,CFS,petechaie,suspected

nuchalrigidity,bulgingfontanelle,andfocalneurologicalsigns haveanincreasedriskof

meningitis.

Thevastmajorityofchildrenwhopresentwithfebrileseizuresdonotdevelopepilepsy.However,

40



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complexfebrileseizuresareassociatedwithanincreasedriskofepilepsy.Thereareotherrisks

factorsforepilepsy,includingneurologicalabnormality,familyhistoryofepilepsy,andshort

duration

of

fever

(


42/44

Intermittent

clobazamvs.placebo

or

no

treatment

Verylow Verylow

Intermittentvs.

continuous

anticonvulsant

Continuous

Phenobarbitalvs.

placeboor

no

treatment

Verylow Lowtoverylow low

Continuousvalproate

vs.placeboorno

treatment

Verylow

Continuous

Phenobarbitalvs.

continuousvalproate

moderate

Balanceof

benefits

versusharms

Intermittentantipyreticsmaybenomoreeffectivethanplacebointreatingepisodesoffeverto

preventseizurerecurrenceinchildrenwithoneormoreprevioussimplefebrileseizures.

Intermittentanticonvulsant(diazepamorclobazam)aremaybemoreeffectiveatreducingtherisk

offebrileseizurerecurrenceinchildrenwithahistoryofsimpleorcomplexfebrileseizures.Howeverdiazepamhasbeenassociatedwithincreasedhyperactivity,lethargy,irritability,andwith

difficultieswithspeech,activitylevel,orsleep.Clobazamisalsoassociatedwithadverseeffects

suchasataxia.Phenobarbitalmaybemoreeffectiveatreducingfebrileseizurerecurrencein

childrenwithahistoryofsimpleorcomplexfebrileseizures.Phenobarbitalismaybeassociated

withcognitiveimpairment,andwithbehaviouralproblemsincludinghyperactivity,irritability,and

42



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aggression.Continuoussodiumvalproatemaybenomoreeffectiveatreducingfebrileseizure

recurrenceinchildrenwithahistoryofsimpleorcomplexfebrileseizures.Seriousadverseevents

which

may

be

associated

with

sodium

valproate

include

hepatotoxicity,

and

haematological

toxicity,bothofwhichmayoccasionallybefatal.Theevidenceisinconclusivewhether

phenobarbitalismoreeffectivethansodiumvalproateatreducingtheproportionofchildrenwith

febrileseizurerecurrence.

Intermittentdiazepamorcontinuousphenobarbitalmaybenomoreeffectiveatreducingtherisk

ofsubsequentepilepsyinchildrenwithfebrileseizures.

Valuesand

preferences

includingany

variabilityand

humanrights

issues

Forfebrile

seizures,

prophylactic

therapy

is

advocated

by

some

because

of

the

concerns

that

such

seizuresleadtoadditionalfebrileseizures,toepilepsy,andperhapseventobraininjury.Moreover,

theynotethepotentialforsuchseizurestocauseparentalanxiety.Addressingparentalanxiety

shouldakeypartofthemanagementoffebrileseizures,asparents'(unspoken)worrywithafirst

seizureisthattheirchildmighthavedied.

Costsand

resourceuse

andanyother

relevant

feasibility

issues

Thenon

specialist

health

care

provider

can

be

trained

to

recognize

and

manage

febrile

seizures.

Finalrecommendation(s)

Childrenwithsimplefebrileseizurescanbediagnosedandmanagedbynonspecialisthealthcareprovidersinlow

andmiddleincomecountries.Insimplefebrileseizures,localstandardsfordiagnosisandmanagementoffever

shouldbefollowedandchildrenshouldbeobservedfor24hours.IntegratedManagementofChildhoodIllnesses

(IMCI)guidelinesshouldbeusedformanagementoffever.

43



44/44

Strengthofrecommendation:STRONG

Prophylactic

treatment

with

intermittent

antipyretics,

intermittent

anticonvulsant

(diazepam

or

clobazam),

or

continuousanticonvulsant(phenobarbitalorvalproicacid)shouldnotbeconsideredforsimplefebrileseizures.

Strengthofrecommendation:STANDARD

Forchildrenwithcomplexfebrileseizures(CFS),observationwithininpatientsettingisrecommendedasthesemay

resultfromanacutedisorderofthecentralnervoussystemorcouldbesimplyaprolongedfebrileseizure.Therefore

theyshouldbereferredtosecondlevelcare.Investigationssuchasbloodtests,lumbarpuncturetodeterminethe

presenceof

underlying

etiology

is

recommended

in

case

of

CFS

depending

on

the

local

context

and

other

clinical

symptoms.

Strengthofrecommendation:STRONG

Prophylacticintermittentdiazepammaybeconsideredinthetreatmentofrecurrentorprolongedcomplexfebrile

seizures(CFS).

Strengthofrecommendation:STANDARD

44

mh evidence prof epilpesy q3 mgt feb seizures 2010 en

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