Rev. Bras. Anestesiol. vol.66 número6

REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

www.sba.com.br

SCIENTIFIC

ARTICLE

Sufentanil

in

combination

with

low-dose

hyperbaric

bupivacaine

in

spinal

anesthesia

for

cesarean

section:

a

randomized

clinical

trial

Alexandre

Dubeux

Dourado

_,

_Ruy

_Leite

_de

_Melo

_Lins

_Filho

_,

Raphaella

Amanda

Maria

Leite

Fernandes

,

Marcelo

Cavalcanti

de

Sá

Gondim

,

Emmanuel

Victor

Magalhães

Nogueira

a_{UniversidadeFederaldePernambuco(UFPE),HospitaldasClínicas,Recife,PE,Brazil}

b_{UniversidadeFederaldePernambuco(UFPE),HospitaldasClínicas,ProgramadeResidênciaMédicaemAnestesiologia,}

Recife,PE,Brazil

Received4April2015;accepted12May2015 Availableonline13September2016

KEYWORDS

Sufentanil; Spinalanesthesia; Bupivacaine; Hyperbaric; Cesareansection

Abstract Adoubleblindrandomizedclinicaltrialofsufentanilasanadjunctinspinal anes-thesiaforcesareansectionand,thereby,beabletoreducethedoseofbupivacaine,alocal anesthetic, with the same result of ananesthetic block with higher doses but with fewer perioperativesideeffects,suchashypotension.

©2016SociedadeBrasileiradeAnestesiologia.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense( http://creativecommons.org/licenses/by-nc-nd/4.0/).

PALAVRAS-CHAVE

Sufentanil; Raquianestesia; Bupivacaína; Hiperbárica; Cesariana

Associac¸ãodesufentaniladosereduzidadebupivacaínahiperbárica emraquianestesiaparacesariana:ensaioclínicorandomizado

Resumo Ensaioclínico randomizadoduplamenteencobertosobreousodosufentanilcomo adjuvanteemraquianestesiaparacesarianae,possibilitandoareduc¸ãodadosedoanestésico local,abupivacaína,comomesmoresultadodebloqueioanestésicocomdosesmaiselevadas, mascommenosefeitoscolateraisnoperioperatório,comohipotensão.

©2016SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Este ´eum artigoOpen Accesssobumalicenc¸aCCBY-NC-ND( http://creativecommons.org/licenses/by-nc-nd/4.0/).

∗_{Correspondingauthor.}

E-mail:rafa.amanda120@gmail.com(R.A.Fernandes).

http://dx.doi.org/10.1016/j.bjane.2015.05.002

Introduction

Compared togeneral anesthesia, neuraxial anesthesiafor

cesarean section (C-section)presents advantages, suchas

reduced risk of intubation failure and aspiration of

gas-tric contents, reduced use of depressants (hypnotics and

opioids),andthemother’sconsciousnessthatallows

moth-ers undergo the birth experience.1,2 _{Spinal anesthesia is}

currently the most widely used technique for C-section,

asit providesintensesensoryblockandrapidinstallation.

However,thistechniquecanbeaccompaniedbysignificant

hypotension,itsmostimportantsideeffect,withreported

incidenceof20---100%.3---5

Several strategies have been described to prevent the

occurrenceofhypotensioninC-section,suchasleftuterine

displacement, crystalloid or colloid administration, lower

limb wrapping, prophylacticuse of ephedrineor

phenyle-phrine,butnoneofthemeliminatedhypotension.6,7

Therelationshipbetweenthelocalanesthetic(LA)dose

used and the occurrence of maternal hypotension is well

established,withhigherdosesrelatedtoahigherincidence

ofhypotension.8_{However,thereductionofLAdoseleadsto}

increasedincidenceofintraoperativepain.3,9

Ithasbeenshownthatthecombinationoflipophilic

opi-oids with local anesthetics in spinal anesthesiaallows LA

dosereductionandpromoteseffectiveanesthesiawithless

sideeffectsonmaternalhemodynamics.10---14

Sufentanil,highlysoluble,enhancesanalgesiaand

com-fortduringsurgery,withashortlatencyperiod(5---10min) anddurationofactionofupto7h.10,15---17_{The useof}

mor-phine, soluble opioid, is recommended to ensure longer

postoperativeanalgesia.10,18

The aim of this study wasto compare the efficacy of

anesthesiaandtheincidenceof sideeffects betweentwo

hyperbaric bupivacaine doses in spinal anesthesia for

C-sectionwithcombinedsufentanilatthelowestdose.

Material

and

methods

After approval by the Ethics Committee, the

random-ized double-blind trial was started with 94 women,

aged 18---45 years, undergoing C-section under spinal

anesthesia. After obtaining written informed consent

and consulting the randomization table, patients were

allocated to one of two study groups: Group A

(bupiva-caine 12.5mg+morphine 80␮g)and Group S (bupivacaine

10mg+morphine80␮g+sufentanil5␮g).Syringes

prepara-tionandspinalanesthesiaadministrationwereperformedby

ananesthesiologistblindedtodatacollection.Allthe inves-tigatorsinvolvedinthestudywereblindedtotheassignment

ofeach group.Pregnantwomenunabletodecideontheir

participationinthe studyor unabletoprovidethe

neces-saryinformation,ASAIVorV,requiringemergencyobstetric

care,withahistoryofhypersensitivityorallergytoanyof

thestudydrugs,andthosewithanycontraindicationtothe

techniqueproposedwereexcluded.

Withthepatientinasittingposition,subarachnoid punc-turewasperformedintheL2---L3,L3---L4orL4---L5interspace,

with25Gor27GQuinckeneedles,andthedrugswere

admin-isteredaccordingtothegroupforwhichitwasrandomized.

Local anesthetics and opioids were delivered in separate

syringesforatotaltimeof15s.The patientswere

imme-diatelyplacedinthesupineposition,manuallyshiftingthe uterustotheleftatanangleof15◦_.

Blood pressure and heart rate measurements were

recorded before spinal anesthesia and at every 3min in

thefirst15min, andat 30and 45min aftertheblockade.

Hypotension was defined as a decrease in systolic blood

pressure(SBP)upto20%frombaselineandcontrolledwith

intravenous ephedrine (5mg). Bradycardia, defined as a

heartratebelow80%ofbaselineorbelow50bpmof

base-linevalue,wastreatedwithintravenousatropine(0.5mg).

Thelevelofsensoryblockat T6dermatomewastestedat

5,10,and15minaftertheblockadebypinprickwitha22G

needle.

Symptomsoradverseevents,suchasnausea,vomiting,

drowsiness, pain above three on the Visual Analog Scale

(VAS>3)orabdominaldiscomfort,inadditiontotheneonate Apgarscoreinthefirstandfifthminute,needtouse

vaso-pressor for hypotension treatment, fetal extraction time,

anddurationofsurgerywererecorded.Abdominalpainor

discomfortduring surgerywastreated withfentanyl bolus

dosesof50␮g,repeatedattheassistant physician

discre-tion.

Postoperative nausea, vomiting, itching, and pain at

rest (VAS>3) at two, six, and 12h after anesthesiawere recorded.

Statistical analysis was performed using the Epi Info®

7.1.3.0 software. Quantitative variables were analyzed

usingmeanand standard deviation (SD)andsubmitted to

theStudentt-testandthefrequencyofqualitativevariables weresubmittedtothechi-squareandFisherexacttests(the

latterwhentheoccurrenceofvariableswaslessthanfive

andthistestcouldbeperformed).

Results

Intotal, 94patients wereselected andsubmittedto

ran-domization,46patientsinGroupAand48inGroupS.There

weretwolossesinGroup Aduetoinadequatecompletion

ofthequestionnaireandonelossin GroupSdue tospinal

anesthesiatotalfailureandneedforasecondpuncture.

Therewasnostatisticallysignificantdifferencebetween

thetwogroupsregardingageandbodymassindex(BMI)of

patientsandgestationalage(Table1).Themostcommonly

usedpuncturesitewasL3---L4,and27Gneedlewasthemost

usedinbothgroups(Table2).

Themeantimeforfetalextractionwas14.16±4.8min

forGroupAand14.51±4.7minforGroupS,andthemean

durationofsurgerywas56.06±11.75min forGroupAand

57.21±10.88minforGroupS(Table3).

Theuseofephedrinetotreathypotensionwassimilarin

bothgroups(30patientsinGroupAand36patientsinGroup S,68.18%and76.6%,respectively)(Table4).

ThelatencytoreachT6dermatomewassimilarinboth

groups,althoughthenumberofpatientswhoreachedthis

levelin5minwashigherinGroupSthaninGroupA(85.11%

vs. 70.45%), but not statistically significant. Over 90% of

patients achieved this level up to 10min in both groups

Table1 Characteristicsofpatients.

GroupA(n=44) GroupS(n=47)

Mean SD Mean SD pa

Age(years) 26.0227 6.36 27.34 5.99 0.3114

BMI(kgm−2_{) 30.64 6.36 32.13 5.43 0.2322}

Gestationalage(weeks) 37.9373 2.32 38.31 1.95 0.3976

SD,standarddeviation. a_{Student’st-test.}

Table2 Spinalpuncturedata.

GroupA GroupS

n=44 % n=47 % pa

Puncturelevel 0.5436

L2---L3 4 9.09% 2 4.26%

L3---L4 37 84.09% 43 91.49%

L4---L5 3 6.82% 2 4.26%

Needle 0.6615

25G 14 31.82% 17 36.17%

27G 30 68.18% 30 63.83%

a_{Chi-squaretest.}

Table3 Surgicaltimes.

GroupA(n=44) GroupS(n=47)

Mean SD Mean SD pa

Durationofbirth(min) 14.16 4.8 14.51 4.7 0.7252

Durationofsurgery(min) 56.06 11.75 57.21 10.88 0.6307

a_{Student’st-test.}

Intraoperativeincidenceofpruritusanddrowsinesswas

higherinGroupS(36.17%and23.4%)thaninGroupA(4.55%

and0%,respectively).

TherewasagreatertendencyofbradycardiainGroupS

(59.57%)thaninGroupA(43.18%),butthisdifferencewas

notstatisticallysignificant.

Therewasnosignificantdifferencebetweengroupsinthe

incidenceofhypotension,nausea,vomiting,decreased

oxy-gensaturationbyhemoglobin(SpO2),abdominaldiscomfort,

andintraoperativepain(Table6).

Table4 Intraoperativeneedofephedrine.a

GroupA(n=44) GroupS(n=47)

n % n %

Yes 30 68.18 36 76.6

No 14 31.82 11 23.4

a_{p=0.8074;chi-square.}

TherewasnosignificantdifferencebetweenApgarscores

atoneand5min,95.45%ofnewbornsinGroupAand95.75%

ofnewbornsinGroupShadscoresbetween7and10at1min

andallinfantshadscorebetween7and10at5min(Table7). Postoperativeevaluation(Table8)showedahigher

inci-dence of pruritus 2h after intrathecal injection in Group

ScomparedtoGroupA(61.7%vs.30.23%,respectively),a

statisticallysignificantdifference.Therewasnosignificant

difference in the incidenceof pruritus duringrevaluation

Table5 LatencytimeofsensoryblocktoreachT6.a GroupA

(n=44)

GroupS (n=47)

n % n %

Upto5min 31 70.45 40 85.11

6---10min 9 20.45 3 6.38

11---15min 1 2.27 3 6.38

Table6 Intraoperativecomplications.

GroupA(n=44) GroupS(n=47)

n % n % p

Hypotension 36 81.82 37 78.72 0.7111a

Bradycardia 19 43.18 28 59.57 0.1178a

Nausea 17 38.64 16 34.04 0.6487a

Vomiting 9 20.45 6 12.77 0.3232a

Pruritus 2 4.55 17 36.17 c_0.0001b

SpO2<95% 3 6.82 1 2.13 0.3504b

Drowsiness 0 0 11 23.4 c_0.0005b

Abdominaldiscomfort 5 11.36 1 2.13 0.1032b

Pain 1 2.27 1 2.13 1.0b

a _Chi-square. b _{Fisher’sexact.} c _p<0.05.

Table7 Apgarscores.

Valor Apgar,1mina _Apgar,5minb

GroupA(n=44) GroupS(n=47) GroupA(n=44) GroupS(n=47)

n % n % n % n %

<7 2 4.55 2 4.26 --- --- ---

---7---10 48 95.45 45 95.74 44 100 47 100

a _{p=0.6663;Fisher’sexact.} b _{p=1;Chi-square}

timesatsixand12h,aswellastheincidenceofnauseaand vomitingin alltimes(2, 6,and12h). Ofthefivepatients

whoexperiencedepisodesof vomitingin thereevaluation

after2h,onlyonepersistedwithvomitinginthe2nd

reval-uation(6h).Theotherfouroccurrencesintherevaluation

at6hcorrespondedtonewcases.

Regardingtheoccurrenceofpainatrest(VAS>3),there

wasahigherincidenceinGroup AcomparedtoGroupSin

therevaluationat6haftertheprocedure(18.18%vs.6.38%, respectively),butstatisticallynotsignificant.Theincidence ofpain(VAS>3)12hafter spinalanesthesia tendedtobe similarbetweengroups(Table9).

Table8 Postoperativesideeffects.

GroupA(n=44) GroupS(n=47) p

n % n %

Pruritus

After2hc _{13 30.23 29 61.7 0.0027}a,c

After6h 13 30.23 18 38.3 0.4212a

After12h 6 13.95 8 17.02 0.6883a

Nausea

After2h 5 11.63 5 12.77 0.8692a

After6h 3 6.98 4 8.51 0.5502b

After12h 4 9.3 1 2.13 0.1538b

Vomiting

After2h 1 2.33 4 8.51 0.2094b

After6h 1 2.33 4 8.51 0.2094b

After12h 0 0 0 0

Table9 Postoperativepainatrest(VAS>3).

GroupA(n=44) GroupS(n=47) p

n % n %

After2h 3 6.82 4 8.51 0.5372b

After6h 8 18.18 3 6.38 0.0795b

After12h 13 29.55 13 27.66 0.0396a,c

a_Chi-square. b _{Fisher’sexact.} c _p<0.05.

Discussion

To obtain adequate anesthesia for C-section, an intense

blockadecovering fromthe sacral (S2---S4) tothe visceral

fibers(T4---T12)is needed.Ablockadewithsuchextension

resultsinhypotensionbyblockingthesympatheticfibers.10

Thelocalanestheticcommonlyusedis0.5%hyperbaric

bupi-vacaineatdosesrangingfrom7.5to15mg.Theuseof10mg

aloneor 8mg combinedwith opioidsis reported as‘‘low

dose’’bysomeauthors,10_{whileothersconsider‘‘lowdose’’}

onlywhenthebupivacainemassdoesnotexceed8mg.3

Althoughtheliteratureshowatrendtowardbupivacaine

dosereduction uptodosesaslow as8mg,either withor

withouttheadditionoflipophilicopioids,reducingthisdose

tolevelsbelow 10mgwithout epidural catheterinsertion

maybeunsafeduetothepotentialriskoffailurein

obtain-inganadequate levelofblockadeor inadequateblockade

duration for surgical time, which increases the need for

intravenousanalgesicagents(fentanyl)orconversionto gen-eralanesthesia.3,8,9

Higherincidenceofintraoperativehypertensionhasbeen

was reported in patients receiving intrathecal sufentanil

at a dose of 5␮g.17 Other studies of sufentanil at doses

ranging from2.5 to 10␮g failedto establish a significant

relationshipbetweentheuseofintrathecalsufentaniland

hypotension,3,4,15,19 _{aresultsimilartothatobservedinour}

study.However, it is possible that the addition of

sufen-tanilisresponsibleforthenon-occurrenceoftheexpected

decreasein the incidenceof hypotensionwith the

hyper-baricbupivacainedosereducedfrom12.5to10mg.

Althoughtherewasahigherincidenceofbradycardiain

patients whoreceived sufentanil, this differencewasnot

statisticallysignificant. Thisrelationship wasnotobserved previouslyinastudythatevaluatedtheincidenceof brady-cardiainpatientsreceivingsufentanil(10␮g)ormorphine

(200␮g)bythesamerouteofadministration.15

Severalstudieshaveshownthatintrathecalsufentanilis

relatedtosedation15,17,19_{andthatsufentanilismore}

sedat-ingthanspinalmorphine(30%vs.5%,respectively).15_These

resultscoincide with thoseobserved by us,asdrowsiness

occurredin23.4%ofpatientsreceivingsufentanilandwas

absentinthegroupthatreceivedonlymorphineasan

adju-vant.

Astudycomparingdifferentdosesofbupivacainealone

forC-sectionunderspinalanesthesiareported35%incidence

ofintraoperativepainwithadoseof8mg,20%withadose

of10mg,andabsent withadose of 12mg.9 _{We found no}

differencesintheoccurrenceofthiseffectwhencomparing

hyperbaricbupivacaine(12.5mg)combinedwithonly

mor-phine withhyperbaric bupivacaine (10mg)combinedwith

morphine and sufentanil. It is probable that the addition

of sufentanil is responsible for maintaining the quality of

analgesiawitha dose reduction,which isin line withthe

resultsobservedinotherstudiesshownthattheadditionof

lipophilicopioiddrasticallyreducestheoccurrenceof

intra-operativepainwhenbupivacaineisusedatdosesbetween

8and10mg.3,9,20

Whentheincidenceofprurituswascomparedbetween

patients who received intrathecal bupivacaine alone and

patients who received sufentanil (10␮g) or morphine

(200␮g)combinedwithbupivacaine,it wasobserved that

theincidencewassignificantlyhigherinpatientsreceiving

sufentanil comparedtothosereceivingmorphine(30% vs.

10%,respectively).15_{Itwasalsoshownthatpruritusresulting}

fromthe use of intrathecal sufentanil is dose-dependent,

rangingfrom34.3%withadoseof2.5␮gto68.6%withadose

of 5␮g.17 Pruritusinducedby intrathecalmorphine isalso

dose-dependent,especiallyindosesabove0.1mg.21_Inour

study,asignificantlyhigherdifferenceinprurituswasseen inpatientsreceivingsufentanil,intheintraoperativeperiod

andatthefirstassessment2hafteranesthesia,sufentanil

actionperiod.

Thus,in thepresent study,thedose reduction of 0.5%

hyperbaric bupivacaine from 12.5 10mg, combined with

sufentanil(5␮g)at thelowestdose, maintainedthesame

qualityofanesthesia, butdidnotreduce theincidenceof

hypotension and increased the incidence of pruritus and

sedation.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

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