Effectsofafentanylpropofol

mixtureonpropofolinjectionpain:a
randomizedclinicaltrial
Efek dari campuran fentanyl-propofol pada nyeri propofol injeksi: uji coba
klinis secara acak..

Background:
Propofolinjectionpainisacommonproblemthatcanbeverydistressingforpatients.We
comparedtheeffectsofinjectionwithsalinefollowedbyinjectionwithafentanyl
propofolmixture,injectionwithfentanylfollowedbyapropofolinjection,andinjection
withsalinefollowedbypropofolaloneonpropofolinjectionpain.
nyeri propofol injeksi adalah masalah umum yang bisa sangat menderita
bagi pasien. Kami membandingkan efek dari injeksi dengan larutan salin
diikuti dengan injeksi dengan campuran fentanyl-propofol, injeksi dengan
fentanyl diikuti dengan injeksi propofol, dan injeksi dengan larutan garam
diikuti oleh propofol saja pada nyeri propofol injeksi.
Methode:

Thepatientswereassignedrandomlytooneofthreegroups.Arubbertourniquetwas
placedontheforearmtoproducevenousocclusionfor1min.Beforeanesthesia
induction,groupC(control,n=50)andgroupM(fentanylpropofolmixture,n=50)
received5mlofisotonicsaline,whilegroupF(fentanyl,n=50)received2g/kgof
fentanyl.Afterthetourniquetwasreleased,groupsCandFreceived5mlofpropofoland
groupMreceived5mlofamixturecontaining20mlofpropofoland4mloffentanyl.At
10safterthestudydrugsweregiven,astandardquestionaboutthecomfortofthe
injectionwasaskedofthepatient.Weusedaverbalratingscaletoevaluatepropofol
injectionpain.StatisticalanalyseswereperformedwithStudentsttestsandFishers
exacttests;P<0.05wasconsideredtoindicatestatisticalsignificance.
Parapasiensecaraacakdiberiobattersebutkesalahsatudaritigakelompok.Sebuah
tourniquetkaretditempatkandilenganuntukmenghasilkanoklusivenaselama1menit.
Sebeluminduksianestesi,kelompokC(kontrol,n=50)dankelompokM(campuran
propofolfentanyl,n=50)menerima5mllarutansalinisotonik,sedangkankelompokF
(fentanyl,n=50)menerima2mg/kgfentanyl.Setelahtourniquetinidilepas,kelompok
CdanFmenerima5mldaripropofoldankelompokMmenerima5mlcampuranyang

mengandung20mlpropofoldan4mlfentanyl.Pada10ssetelahobatstudidiberi,
pertanyaanstandarkepadapasiententangkenyamananinjeksi.Kamimenggunakanskala
penilaianlisanuntukmengevaluasinyeriinjeksipropofol.Analisisstatistikdilakukan
denganStudentttesdantesFisher;P<0,05dianggapuntukmenunjukkansignifikansi
statistik.
Result:
Thedemographicdataweresimilaramongthegroups.IngroupM,thenumberof
patientsreportingpropofolinjectionpainwassignificantlylowerthaningroupsFandC
(bothP<0.001).NopatientingroupForMexperiencedseverepain,whereas24
patients(48%)hadseverepainingroupC(bothP<0.001).
Datademografiyangsamadiantarakelompokyanglain.DalamkelompokM,jumlahpasien
yangmelaporkannyeriinjeksipropofolsecarasignifikanlebihrendahdaripadakelompokFdan
C(keduanyaP<0,001).TidakadapasiendalamkelompokFatauMmengalaminyerihebat,
dimana24pasien(48%)memilikinyerihebatpadakelompokC(keduanyaP<0,001).
Conclucion:

Thisstudyshowsthatafentanylpropofolmixturewasmoreeffectivethanfentanyl
pretreatmentoraplaceboinpreventingpropofolinjectionpain.
Studiinimenunjukkanbahwacampuranfentanylpropofollebihefektifdaripadafentanyl
perlakuanawalatauplasebodalammencegahnyeripropofolinjeksi.

Introduction
Propofolhasgainedwideacceptanceamonganesthesiologistsduetoitsfavorable
inductioncharacteristics,includingitsrapidonsettimeandfasteliminationhalflife.
However,intravenous(i.v.)propofolinjectionsarepainful,makingtheinductionof
anesthesiauncomfortableforthepatientandanesthesiologist[14].
Propofoltelahmemperolehpenerimaanluasdikalanganahlianestesikarenakarakteristik
induksiyangmenguntungkan,termasukwaktuonsetyangcepatdaneliminasicepatparuh.
Namun,intravenasuntikan(i.v.)propofolyangmenyakitkan,membuatinduksianestesitidak
nyamanbagipasiendandokteranestesi[14].

Severalpharmacologicalinterventionshavebeendescribedtoreduceorpreventpropofol
injectionpain[3],includingcoolingordilutingthepropofolsolution,orapplying
propofolintandemwithlocalanesthetics,ondansetron,ketamine,magnesiumsulfate,
nonsteroidalantiinammatorydrugs,oropioids[512].
Beberapaintervensifarmakologistelahdijelaskanuntukmengurangiataumencegahnyeriinjeksi

propofol[3],termasukpendinginataumenipiskansolusipropofol,ataumenerapkanpropofol
seiringdengananestesilokal,ondansetron,ketamine,magnesiumsulfat,obatinflamasinon
steroid,atauopioid[512].

Fentanylgivenjustbeforepropofoldiminishespropofolinjectionpain,butitisunclear
whetherfentanylhasthiseffectwhenusedinamixturewithpropofol[4].Wecompared
theeectsofinjectionwithsalinefollowedbyinjectionwithafentanylpropofolmixture,
injectionwithfentanylfollowedbyapropofolinjection,andinjectionwithsaline
followedbypropofolaloneonpropofolinjectionpain.Wehypothesizedthatafentanyl
propofolmixturemightreducethepainrelatedtopropofolinjectionmoreeffectivelythan
fentanylpretreatmentalone.
Fentanyldiberikansebelumpropofoluntukmenguranginyeriinjeksipropofol,tetapitidakjelas
apakahfentanylmemilikiefekinibiladigunakandalamcampurandenganpropofol[4].Kami
membandingkanefekdariinjeksidenganlarutansalindiikutiolehinjeksidengancampuran
fentanylpropofol,injeksidenganfentanyldiikutidenganinjeksipropofol,daninjeksidengan
larutangaramdiikutiolehpropofolsajapadanyeripropofolinjeksi.Kamiberhipotesisbahwa
campuranfentanylpropofoldapatmengurangirasasakityangterkaitdenganinjeksipropofol
lebihefektifdaripadafentanylperlakuanawalsaja.

MaterialsandMethods
ThisstudywasconductedwithInstitutionalReviewBoardapprovalandwasregistered
withthewww.clinicaltrials.govprotocolregistrationsystem(NCT02203175).Ethical
approval(No.100:25/05/2011)wasprovidedbytheEthicsCommitteeofYeditepe
UniversityHospital,Istanbul,Turkey(Chairperson:Dr.KemalSaricali),onMay25,
2011.Informedconsentwasobtainedfromeachpatient.
PenelitianinidilakukandenganpersetujuanInstitutionalReviewBoarddanterdaftardengan
sistempendaftaranprotokolwww.clinicaltrials.gov(NCT02203175).persetujuanetis(No.100:
25/05/2011)diberikanolehKomiteEtikaRumahSakitUniversitasYeditepe,Istanbul,Turki
(Ketua:Dr.KemalSaricali),padatanggal25Mei2011.Informedconsenttelahdidapatkandari
masingmasingpasien.

StudydatawerecollectedatYeditepeUniversityHospitalfromApril2011toApril2012.
Intotal,150AmericanSocietyofAnesthesiologistsphysicalstatusIIIpatients,aged
1865yearsold,whowerescheduledforelectivesurgerywereenrolled.eexclusion
criteriawerecommunicationdifficulties,psychiatricandneurologicaldisorders,history
ofallergytothestudydrugs,anduseofanalgesicsorsedativedrugswithin24hbefore
surgery.
DatapenelitiandikumpulkandariRumahSakitUniversitasYeditepedariApril2011hingga
April2012.Secaratotal,150MasyarakatAmerikaofAnesthesiologistsstatusfisikpasienIII,

berumur1865tahun,yangdijadwalkanuntukoperasielektifyangterdaftar.kriteriaeksklusi
adalahkesulitankomunikasi,gangguanpsikiatridanneurologi,riwayatalergiterhadapobat
studi,danpenggunaananalgesikatauobatpenenangdalamwaktu24jamsebelumoperasi.

Thestudywasdesignedinaprospective,randomized,anddoubleblindfashion.Patients
wereassignedrandomlytooneofthreegroupsusinganExcel(Microso,Redmond,WA,
USA)generatedrandomizationtable.Nopatientreceivedpremedication.Beforethe
inductionofanesthesia,itwasexplainedtothepatientsthattheywouldbereceivingi.v.
anestheticsthatmightcausepainintheforearm.Onarrivalattheoperatingroomaer
monitoring(ECG,noninvasivebloodpressure,pulseoximeter,andbispectralindex
[BIS]),a20gaugecannulawasinsertedintoaveinonthedorsumofthepatientsnon
dominanthandanda0.9%NaClinfusionwasstartedat5ml/kg/hfor5min.
Penelitianinidirancangdalamprospektif,acak,dandoubleblindmetode.Pasiendiberikan
secaraacakkesalahsatudaritigakelompokmenggunakanExcel(Microsoft,Redmond,WA,
USA)dihasilkansecaratabelrandomization.Tidakadapasienyangmenerimapremedikasi.
Sebeluminduksianestesi,itudijelaskankepadapasienbahwamerekaakanmenerimai.v.
anestesiyangdapatmenyebabkanrasasakitdilenganbawah.Setibanyadiruangoperasisetelah
pemantauan(EKG,tekanandarahnoninvasif,oksimeterdenyutnadi,danindeksbispectral
[BIS]),kanula20gaugedimasukkankepembuluhdarahdipunggungtangannondominan
pasiendan0,9%NaClinfusdimulaipada5ml/kg/jamselama5menit.

Next,thei.v.infusionwasstoppedandthearmwiththei.v.linewaselevatedfor15sto
facilitategravitydrainageofvenousblood.Arubbertourniquetwasplacedonthe
forearmtoproducevenousocclusionfor1min.eanesthesiologistwhopretreatedthe
patientswasblindedtoeachpatientsallocation.Beforeanesthesiainduction,thesubjects
ingroupsC(control,n=50)andM(mixture,n=50)received5mlofisotonicsaline,
whereasthoseingroupF(fentanyl,n=50)received2g/kgoffentanyldilutedwith
salinetoatotalvolumeof5mlasapretreatment(1%propofol[FreseniusKabi,Bad
Homburg,Germany];0.05mg/mlfentanyl[JanssenCilagPty.Ltd.,MacquariePark,
Australia])ataninjectionrateof0.5ml/s.
Selanjutnya,i.v.yanginfusdihentikandanlengandengani.v.yangjalurdinaikanselama15s
untukmemfasilitasigravitasidrainasedarahvena.Sebuahtourniquetkaretditempatkandilengan
untukmenghasilkanoklusivenaselama1menit.dokteranestesiyangpretreatedpasienitutidak
mengetahuimasingmasingpasien.Sebeluminduksianestesi,subjekdikelompokC(kontrol,n
=50)danM(campuran,n=50)menerima5mllarutansalinisotonik,sedangkandikelompokF
(fentanyl,n=50)menerima2mg/kgfentanyldiencerkandenganlarutansalinuntuktotal
volume5mlsebagaiperlakuanawal(1%propofol[FreseniusKabi,BadHomburg,Jermandi
bidang];0,05mg/mlfentanyl[.JanssenCilagPtyLtd,MacquariePark,Australia])padatingkat
suntikan0,5ml/s.

Thedrugswerepreparedbyoneoftheinvestigators,whowasblindedtothestudy

groups.Thepretreatmentsolutionswereidenticalinappearance.Allstudydrugswere
preparedpreoperativelyatroomtemperature.epHvaluesofthefentanyl,propofol,and
fentanylpropofolsolutionsweremeasuredwithapHmeter(InoLab740withterminal
740;WTWGmbH,WeilheiminOberbayern,Germany).ForthepatientsingroupM,the
mixtureoffentanylandpropofolwaspreparedusing20mlofpropofoland4mlof
fentanyl.Aerthetourniquetwasreleased,thepatientsingroupsCandFreceived5ml
ofpropofolwhereasthepatientsingroupMreceived5mlofthefentanylpropofol
mixtureataninjectionspeedof0.5ml/s.
Obatobatanyangdisiapkanolehsalahsatupeneliti,yangtersamarkanterhadapkelompok
belajar.Solusiperlakuanawalidentikdalampenampilannya.Semuaobatstudidisiapkan
sebelumoperasipadasuhukamar.nilaipHdarifentanyl,propofol,danlarutanfentanylpropofol
diukurdenganpHmeter(inoLab740denganterminal740,WTWGmbH,Weilheimin
Oberbayern,Jerman).UntukpasiendalamkelompokM,campurandarifentanildanpropofol
disiapdenganmenggunakan20mlpropofoldan4mlfentanyl.Setelahtourniquetinidilepas,
pasiendalamkelompokCdanFmenerima5mldaripropofolsedangkanpasiendikelompokM
menerima5mlcampuranpropofolfentanylpadakecepataninjeksi0,5ml/s.
At 10 s a er the study drugs had been given, a standard ques- tion about the
comfort of the injection was asked of the patient. We used a verbal rating
scale (VRS) to evaluate the severity of pain due to the injection of propofol
[5,10-12]: 0, none (negative response to questioning); 1, mild pain (pain
reported only in re- sponse to questioning without any behavioral signs); 2,
moderate pain (pain reported in response to questioning and accompanied
by behavioral signs or pain reported spontaneously without questioning); or
3, severe pain (strong vocal response or response accompanied by facial
grimacing, arm withdrawal, or tears). All patients were able to answer the
question; additionally, in all pa- tients the BIS was above 80 at the time of
questioning.
Pada10ssetelahobatstuditelahdiberikan,pertanyaanstandartentangkenyamananinjeksi
dimintapasien.Kamimenggunakanskalapenilaianverbal(VRS)untukmengevaluasikeparahan
nyeriakibatsuntikanpropofol[5,1012]:0,tidakada(tanggapannegatifmempertanyakan);1,
nyeriringan(nyeridilaporkanhanyadalammenanggapipertanyaantanpatandatandaperilaku);
2,nyerisedang(nyeridilaporkandalammenanggapipertanyaandandisertaidengantandatanda
perilakuatausakitdilaporkansecaraspontantanpamempertanyakan);atau3,nyerihebat
(responvokalyangkuatataurespondisertaidenganwajahmeringis,lenganpenarikandiri,atau
airmata).Semuapasienmampumenjawabpertanyaan;tambahan,padasemuapasienBISadalah
diatas80padasaatinterogasi.

theremainingdoseofpropofolandfentanylwasthengiventocompletetheinductionof
anesthesia.ecompleteinductiondosewas2mg/kgofpropofoland2g/kgoffentanyl.
Allpatientsweregiven0.5mg/kgofatracuriumformusclerelaxation.Becausegroups
FandMhadalreadyreceived2g/kgoffentanyl,onlythepatientsingroupCreceived

2g/kgoffentanylaerthemusclerelaxant.Aerorotrachealintubation,anesthesiawas
maintainedwith1.02.0%sevouraneand60%nitrousoxideinoxygenwithcontrolled
mechanicalventilation.
dosisyangtersisadaripropofoldanfentanilkemudiandiberikanuntukmenyelesaikaninduksi
anestesi.dosisinduksilengkapadalah2mg/kgpropofoldan2mg/kgfentanyl.Semuapasien
diberi0,5mg/kgatracuriumuntukrelaksasiotot.KarenakelompokFdanMsudahmenerima2
mg/kgfentanyl,hanyapasiendalamkelompokCmenerima2mg/kgfentanylsetelahrelaksan
otot.SetelahintubasiOrotracheal,anestesidipertahankandengan1,02,0%sevofluranedan60%
nitrousoxideoksigendenganventilasimekanisdikendalikan.

theprimaryoutcomewasacompleteresponse(noinjectionpain,VRS=0).the
secondaryoutcomewaspropofolinjectionpain
hasilprimeradalahresponlengkap(tidakadainjeksinyeri,VRS=0).hasilsekunderadalah
nyeriinjeksipropofol.

Statisticalanalysis
Propofolinjectionpainwastheprimaryoutcome.Thereportedincidenceofpropofol
injectionpainis~70%;todecreasethisincidenceto35%,itwascalculatedthat49
patientswouldbeneededineachgroupwithatypeIerrorof0.05andpowerof90%.
Duetopossiblesubjectdropout,50patientspergroupwereenteredintothestudy.
nyeriinjeksipropofoladalahhasilprimer.Insidenyangdilaporkansakitpropofolinjeksiadalah
~70%;untukmengurangiinsidenini35%,itudihitungbahwa49pasienakandiperlukandalam
setiapkelompokdengantipeIerror0,05dankekuatan90%.Karenamungkinsubjekdropout,
50pasienperkelompokyangdimasukkankedalampenelitian.

DemographicdatawerecomparedusingStudentsttest.Fishersexacttestand 2tests
wereusedtoassessdierencesbetweencategoricalvariables.P<0.05wasconsideredto
indicatestatisticalsignicance.
Datademografidibandingkandenganmenggunakanstudentttes.Fishertesdan2tes
digunakanuntukmenilaiperbedaanantaravariabelkategori.P<0,05dianggapuntuk
menunjukkansignifikansistatistik.

Results
Intotal,150patientswerestudied.Fig.1showsaflowchartofthestudy,andTable1
showsthedemographicdataforthepatients.therewasnosignificantdifferenceinage,
weight,orsexamongthethreegroups.theincidenceandseverityofpropofolinjection
painareshowninTable2.

Secaratotal,150pasientelahditeliti.Gambar.1menunjukkandiagramalirpenelitian,danTabel
1menunjukkandatademografisuntukpasien.tidakadaperbedaanyangsignifikandalamusia,
beratbadan,atauseksantaratigakelompok.insidendankeparahandaripropofolnyeriinjeksi
ditunjukkanpadaTabel2.

Inallcases,itwaspossibletoobtainclearanswersfromthepatientbeforethepatient
becameanesthetized.theoverallincidenceofpropofolinjectionpainwas100%(50/50)
ingroupC,92%(46/50)ingroupF,and64%(32/50)ingroupM.Theoverallincidence
ofpropofolinjectionpainingroupFwasnotdifferentfromthatingroupC,whereasthe
incidenceingroupMwassignificantlylowerthanthatingroupC(P=0.0001).
ComparedwithgroupF,theincidenceofpropofolpainingroupMwassignificantly
lower(P=0.001).
Dalamsemuakasus,adakemungkinanuntukmendapatkanjawabanyangjelasdaripasien
sebelumpasienmenjaditeranestesi.insidenkeseluruhannyeripropofolinjeksiadalah100%
(50/50)digrupC,92%(46/50)dalamkelompokF,dan64%(32/50)dalamkelompokM.
keseluruhaninsidennyeripropofolinjeksidikelompokFtidakberbedadariyangdikelompok
C,sedangkankejadiandigrupMsecarasignifikanlebihrendahdibandingkanpadakelompokC
(P=0,0001).DibandingkandengankelompokF,insidennyeripropofoldalamkelompokM
secarasignifikanlebihrendah(P=0,001).

IngroupC,48%ofthepatients(24/50)experiencedseverepain,whereasnopatientdid
ingroupsFandM(significancebetweengroupFandgroupMcomparedwithgroupC,P
=0.0001and0.0001,respectively).
DalamkelompokC,48%daripasien(24/50)mengalaminyerihebat,sedangkantidakadapasien
lakukandikelompokFdanM(signifikansiantarakelompokFdankelompokMdibandingkan
dengankelompokC,P=0,0001dan0,0001,masingmasing).

TheincidenceofpatientswithmoderatepainwassignificantlyloweringroupM(16%;
8/50)thaningroupC(40%;20/50;P=0.013).Therewasnodifferenceintheincidence
ofmoderatepainbetweengroupsFandC.
InsidenpasiendengannyerisedangsecarasignifikanlebihrendahpadakelompokM(16%;
8/50)dibandingkandengankelompokC(40%;20/50;P=0,013).Tidakadaperbedaandalam
kejadiannyerisedangantarakelompokFdanC.

InbothgroupsFandM,theincidenceofmildpainwassignificantlyhigherthaninthe
controlgroup(P=0.009and0.0002,respectively).Nodifferencewasfoundbetween
groupsFandMwithrespecttomildpain.
PadakeduakelompokFdanM,kejadiannyeriringansecarasignifikanlebihtinggidibandingkan
dengankelompokkontrol(P=0,009dan0,0002,masingmasing).Tidakadaperbedaanyang
ditemukanantarakelompokFdanMsehubungandengansakitringan.

ThepHvaluesofthepropofol,fentanyl,andfentanylpropofolsolutionswere8.04,4.45,
and7.42,respectively.
NilaipHdaripropofol,fentanil,danfentanilpropofollarutanadalah8.04,4.45,dan7.42,
masingmasing.

Discussion
Ourresultsindicatethatthemixtureoffentanylandpropofolsignificantlyreducedthe
incidenceandseverityofpropofolinjectionpaincomparedwiththecontrolgroup.In
contrast,fentanylpretreatmentdidnotreducetheincidenceorseverityofpaincompared
withthecontrolgroup.
Hasilkamimenunjukkanbahwacampuranfentanyldanpropofolsecarasignifikanmengurangi
kejadiandankeparahannyeripropofolinjeksidibandingkandengankelompokkontrol.
Sebaliknya,fentanylperlakuanawaltidakmengurangitimbulnyaataukeparahannyeri
dibandingkandengankelompokkontrol.

Althoughthemechanismunderlyingpropofolinjectionpainisunclear,manyfactors
affecttheincidenceofpain,includingthesiteofinjection,sizeofthevein,speedof
injection,propofolconcentrationintheaqueousphase,bufferingeffectoftheblood,
speedofintravenouscarrierfluid,temperatureofthepropofolsolution,syringematerial,
andtheconcomitantuseofdrugs(e.g.,localanestheticsandopioids)[1,2].
Meskipunmekanismeyangmendasarinyeripropofolinjeksitidakjelas,banyakfaktoryang
mempengaruhitimbulnyanyeri,termasuktempatsuntikan,ukuranvena,kecepataninjeksi,
konsentrasipropofoldalamfaseair,penyanggaefekdarah,kecepatanpembawaintravenafluid,
suhularutanpropofol,bahanjarumsuntik,danpenggunaanbersamaanobat(misalnya,anestesi
lokaldanopioid)[1,2].

Severalmethodshavebeendescribedtoreducepropofolinjectionpain,includingtheuse
ofalargerveinandpretreatmentwithpharmacologicalagentssuchaslidocaine,opioid
analgesics,ketamine,meperidine,metoclopramide,diphenhydramine,magnesium
sulfate,andnonsteroidalantiinflammatoryagents[415].theeffectsoftemperatureand
dilutionaswellasvaryingtheinfusionratehavealsobeenstudied[1619].
Beberapametodetelahdijelaskanuntukmengurangirasasakitpropofolinjeksi,termasuk
penggunaanvenayanglebihbesardanperlakuanawaldenganagenfarmakologisseperti
lidokain,analgesikopioid,ketamine,domperidone,metoclopramide,diphenhydramine,
magnesiumsulfat,dannonsteroidantiinflammatoryagents[415].pengaruhsuhudandilusi
sertamemvariasikankecepataninfusjugatelahdipelajari[1619].

Propofolinjectionpaincanbeimmediateordelayed.Ithasbeensuggestedthat
immediatepainresultsfromadirectirritanteffect,whereasdelayedpainmaybecaused
byanindirecteffectviathekinincascade[20].
Propofolnyeriinjeksidapatsegeraatauditunda.Telahdisarankanbahwahasilnyerilangsung
dariefekiritasilangsung,sedangkannyeritertundamungkindisebabkanolehefektidak
langsungmelaluikinincascade[20].

Thesiteofactionofopioidsinreducingpropofolinjectionpainmaybecentralor
peripheral[21].Opioidreceptorsonperipheralterminalafferentnervescanmediate
potentantinociceptiveeffects[22].
Lokasiaksiopioiddalammengurangirasasakitinjeksipropofolmungkinpusatatauperifer[21].
reseptoropioidpadaperifersarafaferenterminaldapatmemediasiampuhefekantinociceptive
[22].

Inthisstudy,weusedatourniquettoisolatethearmveinsfromtherestofthecirculation.
ishasbeensuggestedtobeausefulmodelforstudyingtheperipheralactionsofadrug
[23].
Dalamstudiini,kamimenggunakantourniquetuntukmengisolasipembuluhdarahlengandari
sisasirkulasi.yaitutelahdiusulkanuntukmenjadimodelyangbergunauntukmempelajari
tindakanperiferdariobat[23].

ThepHvaluesofthepropofol,fentanyl,andfentanylpropofolsolutionsweremeasured
inourlaboratory(8.04,4.45,and7.42,respectively).BecausethepHvalueoffentanylis
lowerthanthatofpropofol,thepHvalueofthepropofolfentanylmixturewaslowerthan
thatofpropofolalone.Erikssonetal.[24]reportedthatdecreasingthepHofpropofol
resultedinalowerconcentrationofpropofolintheaqueousphase.
NilaipHdaripropofol,fentanil,danlarutanfentanylpropofoldiukurdilaboratoriumkami(8.04,
4.45,dan7.42,masingmasing).KarenanilaipHfentaniladalahlebihrendahdaripropofol,nilai
pHdaricampuranpropofolfentaniladalahlebihrendahdaripropofolsendiri.Erikssonetal.[24]
melaporkanbahwapenurunanpHpropofolmengakibatkankonsentrasiyanglebihrendahdari
propofoldalamfaseberair.

KlementandArndt[25]suggestedthattheconcentrationofpropofolintheaqueous
phasewasadeterminingfactorinpropofolinjectionpain.Inabolusinjection,onlythe
outeraqueousphasecomesintocontactwiththeintimaofthevein,andvenouspainon
administrationoftheirritatingagentmaybecausedprimarilybytheconcentrationofthe
irritatingagentintheaqueousphase[26].LoweringthepHvalueofpropofolbymixing
itwithfentanylmayexplainthedecreasedincidenceofpropofolinjectionpain.Helmeret
al.[26]reportedasignificantreductionintheincidenceofpropofolinjectionpain,from

40to16%,withtheuseoffentanylbeforepropofol.eseincidencesaremuchlowerthan
theonesinourstudy.Inourstudy,painincidencewas100%inthecontrolgroupand
92%inthefentanylpretreatmentgroup.esedifferencesmaybeduetomethodological
differencesbetweenthetwostudies.InHelmersstudy[26],patientswereaskedabout
painafterreceiving1.5mg/kgofpropofolandtheBISwasnotmonitored.Itispossible
thatafterthisdoseofpropofol,thepatientsweretoodeeplysedatedtoanswerthe
questionaboutpaincorrectly.ismayexplainwhythereportedincidencewassolow
comparedwiththatinourstudy.Anotherreasonmaybetheveinandi.v.cannulasize(17
vs.20G)usedintheirstudycomparedwithours,whichmayinfluencetheincidenceof
propofolinjectionpain[27].
KlementdanArndt[25]menyarankanbahwakonsentrasipropofoldalamfaseairadalahfaktor
penentudalamsakitpropofolinjeksi.Dalaminjeksibolus,hanyafaseberairluardatangke
dalamkontakdenganintimadarivena,dannyerivenapadapemberianagenmenjengkelkan
dapatdisebabkanterutamaolehkonsentrasiagenmenjengkelkandifaseair[26].Menurunkan
nilaipHpropofoldenganmencampurnyadenganfentanyldapatmenjelaskaninsidenpenurunan
nyeripropofolinjeksi.Helmeretal.[26]melaporkanpenurunanyangsignifikandalaminsiden
nyeripropofolinjeksi,dari40menjadi16%,denganpenggunaanfentanylsebelumpropofol.
insideninijauhlebihrendahdaripadayangdalampenelitiankami.Dalampenelitiankami,
kejadiannyeriadalah100%padakelompokkontroldan92%padakelompokfentanil
pretreatment.perbedaanperbedaaninimungkinkarenaperbedaanmetodologiantaraduastudi.
DalamstudiHelmerini[26],pasiendimintatentangrasasakitsetelahmenerima1,5mg/kg
propofoldanBIStidakdipantau.Adakemungkinanbahwasetelahdosisinipropofol,pasien
terlaludalamdibiusuntukmenjawabpertanyaantentangrasasakitdenganbenar.adalah
mungkinmenjelaskanmengapakejadiandilaporkansangatrendahdibandingkandenganyang
dalampenelitiankami.Alasanlainmungkinvenadani.v.Ukurankanula(17vs20G)yang
digunakandalampenelitianmerekadibandingkandengankita,yangdapatmempengaruhi
timbulnyanyeripropofolinjeksi[27].

Whenmixingtwodrugs,majorconcernsarecompatibilityandthestabilityofthe
mixture.Inourstudy,noprecipitationwasobservedinthesyringe.Stewartetal.[27]
statedthatpropofolandfentanylwerecompatibleandstablewhenmixedtogether.e
subjectivenatureofthefourpointinjectionpainevaluationscaleisalimitationofour
study.Anotherlimitationisthatthismethodcannotbeappliedwithouttourniquetuse.
Ketikamencampurduaobat,kekhawatiranutamaadalahkompatibilitasdanstabilitascampuran.
Dalampenelitiankami,tidakadapresipitasiyangdiamatididalamspuit.Stewartetal.[27]
menyatakanbahwapropofoldanfentaniladalahkompatibeldanstabilbiladicampurbersama
sama.sifatsubjektifdariempattitikskalaevaluasinyeriinjeksiadalahketerbatasandari
penelitiankami.Keterbatasanlainadalahbahwametodeinitidakdapatditerapkantanpa
menggunakantourniquet.

Inconclusion,fentanylmixedwithpropofolreducedinjectionpainsignificantly

comparedwiththecontrolandfentanylpretreatmentgroups.
Kesimpulannya,fentanyldicampurdenganpropofolmengurangirasasakitinjeksisecara
signifikandibandingkandengankontroldanfentanilkelompokperlakuanawal.

References
1. JalotaL,KaliraV,GeorgeE,ShiYY,HornussC,RadkeO,etal.Preventionofpainoninjection
ofpropofol:systematicreviewandmetaanalysis.BMJ2011;342:d1110.
2. TanCH,OnsiongMK.Painoninjectionofpropofol.Anaesthesia1998;53:46876.
3. MarikPE.Propofol:therapeuticindicationandsideeffect.CurrPharmDes2004;10:363949.
4. PicardP,TramrMR.Preventionofpainoninjectionwithpropofol:aquantitativesystematic
review.AnesthAnalg2000;90:9639.
5. McCrirrickA,HunterS.Painoninjectionofpropofol:theeffectofinjectatetemperature.
Anaesthesia1990;45:4434.
6. StokesDN,RobsonN,HuttonP.Effectofdilutingpropofolontheincidenceofpainoninjection
andvenoussequelae.BrJAnaesth1989;62:2023.
7. SaadawyI,ErtokE,BokerA.Painlessinjectionofpropofol:pretreatmentwithketaminevs
thiopental,meperidine,andlidocaine.MiddleEastJAnaesthesiol2007;19:63144.
8. AmbeshSP,DubeyPK,SinhaPK.Ondansetronpretreatmenttoalleviatepainonpropofol
injection:arandomized,controlled,doubleblindedstudy.AnesthAnalg1999;89:1979.
9. IyilikciL,BalkanBK,GkelE,GnerliA,EllidokuzH.eeectsofalfentanilorremifentanil
pretreatmentonpropofolinjectionpain.JClinAnesth2004;16:499502.
10. BasaranogluG,ErdenV,DelatiogluH,SaitogluL.Reductionofpainoninjectionofpropofol
usingmeperidineandremifentanil.EurJAnaesthesiol2005;22:8902.
11. KwakK,KimJ,ParkS,LimD,KimS,BaekW,etal.Reductionofpainoninjectionof
propofol:combinationofpretreatmentofremifentanilandpremixtureoflidocainewithpropofol.
EurJAnaesthesiol2007;24:74650.
12. ApiliogullariS,KelesB,ApiliogullariB,BalasarM,YilmazH,DumanA.Comparisonof
diphenhydramineandlidocaineforpreventionofpainaerinjectionofpropofol:adoubleblind,
placebocontrolled,randomizedstudy.EurJAnaesthesiol2007;24:2358.
13. KooSW,ChoJS,KimYK,HamKD,HwangJH.Smalldoseketaminereducesthepainof
propofolinjection.AnesthAnalg2006;103:14447.
14. MemisD,TuranA,KaramanliogluB,StN,PamukuZ.euseofmagnesiumsulfatetoprevent
painoninjectionofpropofol.AnesthAnalg2002;95:6068.
15. WalkerBJ,NealJM,MulroyMF,HumsiJA,BittnerRC,McDonaldSB.Lidocainepretreatment
withtourniquetversuslidocainepropofoladmixtureforattenuatingpropofolinjectionpain:a
randomizedcontrolledtrial.RegAnesthPainMed2011:36:415.
16. ParmarAK,KoayCK.Painoninjectionofpropofol.Acomparisonofcoldpropofolwith
propofolpremixedwithlignocaine.Anaesthesia1998;53:7983.

17. KlementW,ArndtJO.Painoninjectionofpropofol:eectsofconcentrationanddiluent.BrJ
Anaesth1991;67:2814.
18. GrauersA,LiljerothE,AkesonJ.Propofolinfusionratedoesnotaectlocalpainoninjection.
ActaAnaesthesiolScand2002;46:3613.
19. ShimizuT,InomataS,KiharaS,ToyookaH,BrimacombeJR.Rapidinjectionreducespainon
injectionwithpropofol.EurJAnaesthesiol2005;22:3946.
20. BriggsLP,ClarkeRS,DundeeJW,MooreJ,BaharM,WrightPJ.Useofdiisopropylphenolas
mainagentforshortprocedures.BrJAnaesth1981;53:1197202.
21. JamesMK,FeldmanPL,SchusterSV,BilottaJM,BrackeenMF,LeightonHJ.Opioidreceptor
activityofG187087B,anovelultrashortactinganalgesicinisolatedtissues.JPharmacolExper
1991;259:7128.
22. RahmanAlRefaiA,AlMujadiH,PetrovaIvanovaM,MarzoukHM,BatraYK,AlQattanAR.
Preventionofpainoninjectionofpropofol:acomparisonofremifentanilwithalfentanilin
children.MinervaAnesthesiol2007;73:21923.
23. BorazanH,ErdemTB,KececiogluM,OtelciogluS.Preventionofpainoninjectionofpropofol:
acomparisonoflidocainewithdierentdosesofparacetamol.EurJAnaesthesiol2010;27:253
7.
24. ErikssonM,EnglessonS,NiklassonF,HartvigP.EectoflignocaineandpHonpropofol
inducedpain.BrJAnaesth1997;78:5026.
25. KlementW,ArndtJQ.Painoninjectionofpropofol:eectsofconcentrationanddiluent.BrJ
Anaesth1991;67:2814.
26. HelmersJH,KraaijenhagenRJ,LeeuwenLV,ZuurmondWW.Reductionofpainoninjection
causedbypropofol.CanJAnaesth1990;37:2678.
27. StewartJT,WarrenFW,MaddoxFC,ViswanatanK,FoxJL.Thestabilityofremifentanil
hydrochlorideandpropofolmixturesinpolypropylenesyringesandpolyvinylchloridebagsat22
degrees24degreesC.AnesthAnalg2000;90:14501.