Combinação de levobupivacaína em dose baixa e fentanil para raquianestesia em cirurgia anorretal

REVISTA

BRASILEIRA

DE

ANESTESIOLOGIA

www.sba.com.br

SCIENTIFIC

ARTICLE

Low-dose

levobupivacaine

plus

fentanyl

combination

for

spinal

anesthesia

in

anorectal

surgery

Mehtap

Honca

_,

_Necla

_Dereli

_,

_Emine

_Arzu

_Kose

_,

_Tevfik

_Honca

_,

Selcen

Kutuk

,

Selma

Savas

Unal

,

Eyup

Horasanli

a_{DepartmentofAnesthesiologyandReanimation,KeciorenTrainingandResearchHospital,Ankara,Turkey}

b_{DepartmentofAnesthesiologyandReanimation,IstanbulMedipolUniversity,MedipolMegaHospital,Istanbul,Turkey} c_{DepartmentofMedicalBiochemistry,GulhaneMilitaryMedicalAcademy,Ankara,Turkey}

Received19November2013;accepted15January2014 Availableonline20February2014

KEYWORDS Hyperbaric levobupivacaine; Fentanyl; Spinal; Anorectalsurgery Abstract

Background: theaimofthisstudywastoinvestigatetheeffectsofspinalanesthesiausingtwo differentdosesoffentanylcombinedwithlow-doselevobupivacaineinanorectalsurgery. Methods:inthis prospective,double-blindstudy,52 American Society ofAnaesthesiologists I---IIpatientsscheduledforelectiveanorectalsurgerywererandomizedintotwogroups.The patientsingroupIreceivedintrathecal2.5mghyperbariclevobupivacaineplus12.5␮gfentanyl andingroupIIreceivedintrathecal2.5mghyperbariclevobupivacaineplus25_␮gfentanyl.All thepatientsremainedintheseatedpositionfor5minaftercompletionofthespinalanesthesia. Sensoryblockwasevaluatedwithpin-pricktestandmotorblockwasevaluatedwithamodified Bromagescale.

Results:motorblockwasnotobservedinbothofthegroups.Thesensoryblockwaslimited totheS2levelingroupI,andS1levelingroup II.Noneofthepatients requiredadditional analgesicsduringtheoperation.Timetotwo-segmentregressionwasshorteringroupI com-paredwithgroupII(p<0.01).OnepatientingroupIand5patients ingroupIIhadpruritus. Hemodynamicparameterswerestableduringtheoperationinbothofthegroups.

Conclusion: spinalsaddleblockusinghyperbariclevobupivacainewithboth12.5_␮gand25_␮g fentanylprovidedgoodqualityofanesthesiawithoutmotorblockforanorectalsurgeryinthe proneposition.

© 2014SociedadeBrasileirade Anestesiologia.Publishedby ElsevierEditoraLtda.Allrights reserved.

∗_{Correspondingauthor.}

E-mail:mehtaphonca@hotmail.com(M.Honca).

0104-0014/$–seefrontmatter©2014SociedadeBrasileiradeAnestesiologia.PublishedbyElsevierEditoraLtda.Allrightsreserved.

PALAVRAS-CHAVE Levobupivacaína; Fentanil; Raquianestesia; Cirurgiacolorretal

Combinac¸ãodelevobupivacaínaemdosebaixaefentanilpararaquianestesiaem

cirurgiaanorretal

Resumo

Justificativa:Oobjetivo deste estudofoi investigar osefeitos daraquianestesia comouso deduasdosesdiferentesdefentanilem combinac¸ãocomdosebaixadelevobupivacaína em cirurgiaanorretal.

Métodos: Nesteestudoprospectivoeduplo-cego,52pacientescomestadofísicoASAI-II, pro-gramadosparacirurgiaeletivaanorretal,foramrandomicamentealocadosemdoisgrupos.Os pacientesdoGrupoIreceberam2,5mgdelevobupivacaínahiperbáricamais12,5␮gdefentanil porviaintratecaleosdoGrupoIIreceberam2,5mgdelevobupivacaínahiperbáricamais25␮g defentanilporviaintratecal.Todospermaneceramemposic¸ãosentadaporcincominutosapós otérminodaraquianestesia.Obloqueiosensorialfoiavaliadocomotestedapicadadeagulha eobloqueiomotorcomaescalamodificadadeBromage.

Resultados: Obloqueiomotor não foiobservado em ambosos grupos.O bloqueiosensorial limitou-seaonívelS2noGrupoIeS1noGrupoII.Nenhumdospacientesprecisoudeanalgésico suplementarduranteaoperac¸ão.OtempoderegressãodedoisseguimentosfoimenornoGrupo Iemcomparac¸ãocomoGrupoII(p<0,01).UmpacientedoGrupoIecincodoGrupoII apresen-taramprurido.Osparâmetroshemodinâmicospermaneceramestáveisduranteacirurgia em ambososgrupos.

Conclusão:Obloqueioespinhalemselacomousodelevobupivacaínahiperbárica,tantocom 12,5␮gquanto com25␮gdefentanil,proporcionaboaqualidadedeanestesiasembloqueio motorparacirurgiaanorretalemdecúbitoventral.

©2014SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Todosos direitosreservados.

Introduction

Spinalanesthesiaforanorectalsurgeryisapopularand com-monlyusedmethodcharacterizedbyrapidonsetandoffset, easymobilizationandshorthospitalstory.1

Levobupivacaine hydrochloride is the pure S(-)-enantiomer of racemic bupivacaine with less effects to cardiovascular and central nervous system than bupivacaine.2_{Bothhyperbariclevobupivacaineandisobaric}

levobupivacaine have been used in anorectal surgery.3---5

Howevertherearenotenoughdatayet,whetheroneform issuperiortotheother.Hyperbariclocalanestheticsusedin spinalsaddleblockinthepronepositionhavesome disad-vantages.Patientsarerecommendedtostay inthesitting positionforseveralminutesafterintrathecaladministration topreventtheoccurrenceofhypotension. Alsohyperbaric localanestheticsolutionsmightcausehighlevelsofspinal anesthesia.6,7 _{The sideeffects can be reducedwith using}

lowdosesoflocalanesthetics. Adjuvants suchasfentanyl andsufentanilpotentiatetheafferentsensoryblockadeand facilitatereductionsinthedoseoflocalanesthetics.8 _The

aimofthisprospective,double-blind,randomizedtrialwas tocomparethedifferencesinsensoryandmotorblockade, patient and surgeon satisfaction and complications of intrathecal2.5mghyperbariclevobupivacaineplus12.5␮g fentanylwithintrathecal2.5mghyperbariclevobupivacaine plus25␮gfentanyl.

Materials

and

methods

After approval from the Hospitals Ethics Committee and obtainingpatients’writteninformedconsent,52patients, aged>18years,withAmericanSocietyofAnaesthesiologists

(ASA) physical status I and II scheduled for ambulatory anorectalsurgery,wereincludedinthisstudy.

Patients were randomized into two groups using a computer-generated randomization sequence with sealed envelopes. Patients with abnormal coagulation profiles, severecardiopulmonarydisease,diabetes,peripheral neu-ropathy,infectionattheinjectionsite,markedscoliosis,and patientsreceivingchronicanalgesictherapywereexcluded from the study. None of the patients received premedi-cation. Patients were monitored with electrocardiogram, noninvasive arterial blood pressure and pulseoximetry in theoperatingroom.A20-Gcannulawasinsertedatthe dor-sumofthelefthandand8mL/kg/hof0.9%sodiumchloride infusionwasestablished1hbeforeinitiationoftheregional block.GroupI(n=26)received2.5mghyperbaric levobupi-vacaine 0.5% (5mg/mL, Chirocaine, Abbott Laboratories, NorthChicago,IL,USA)plus12.5␮gfentanylwhereasGroup IIreceived(n=26)2.5mghyperbariclevobupivacaine0.5% (5mgml,Chirocaine, Abbott Laboratories,North Chicago, IL,USA)plus25␮gfentanyl.Bothofthesolutionswere asep-ticallypreparedbyananesthesiologistblindedtothestudy. Allsolutionswerecompletedtoatotalvolumeof2mLwith 10%dextrosesolution.Thespecificgravityofthesolutions wasdeterminedwitharefractometer(T2-NE,AtagoCo.Ltd, Japan),measuredat37◦C.Thespecificgravityofthe mix-tureusedingroupIwas1025gmL−1andwas1020gmL−1in group II. Duetothe specificgravity of cerebrospinalfluid is1003---1008gmL−1at37◦C,thesemixtureswereaccepted ashyperbaric.SpinalanesthesiawasperformedattheL4-5 or L5-S1intervertebralspaceusinga25G Quincketypeof spinalneedleintheseatedposition.The testsolutionwas injectedslowlyin 2minandthepatientswerekeptinthe sitting positionfor 5min toachieve sufficient block.

Sen-soryblockwasevaluatedbythepin-prickmethodatevery 2min until the sufficient block reached the S4 level and testing wasconductedat every5minuntilthe endof the operation. After sitting for 5min patients wereplaced in theproneposition.Motorblockwasevaluatedaccordingto a modified Bromage scale (0:nomotor block, 1:inability toraise extended legs, 2: inability toflex knees, able to movefeet,3:inabilitytoflexankle points).Onsettimeof S4levelsensoryblock(timetoreadinessforsurgery), max-imumlevelofsensoryblock,timeto2segmentregression, time tourination andtime tofirst analgesic requirement wereevaluatedbyanobserverblindedtothestudygroups andrecorded.Postoperativesideeffectslikenausea, vomi-ting,headacheandprurituswererecordedbynursingstaff. Diclofenac sodium 75mg intramuscular (IM) was used for rescue analgesiaandfirstanalgesiarequirementtimewas recorded.Hypotensionwasdefinedasadecreaseinsystolic arterial blood pressure>20% of baseline and was treated with intravenous (IV) 5---10mg bolus doses of ephedrine. Bradycardiawasdefinedasheartrate<60beatperminute andwastreated with0.01mg/kg bolus dosesof atropine. After completion of the surgery, patients were asked to rate the quality of their anesthesia using a 4 point scale (1:Perfect,2:Satisfactory,comfortablebut somefeelings ofpressureortraction,3:Poor,discomfortbecauseof feel-ingintensepressureortraction,4:Worst:Majordiscomfort becauseofpain).

ThestatisticalanalysiswasperformedusingSPSSfor Win-dowsversion10.0.1.Thesamplesizewascalculated,based on80%power,tobeabletodetecta25min(min)difference in mean timeto sensory block recovery.Pre-study power analysisusingourpopulationmeanandstandarddeviation suggestedthat24patientsineachgroupwouldbesufficient todetectadifferenceof25minassumingatypeIerrorof5%. Datawerepresentedasmean±standarddeviation,median (minimum---maximum) or frequencies as appropriate. Stu-dent’st-testwasperformedforanalysisoftheparametric dataandMann---WhitneyUtestwasperformedforanalysis ofthenon-parametricdata.Resultswereconsidered statis-ticallysignificantifp<0.05.

Results

Fifty-twopatientswereenrolledinthestudy.Nosignificant differencewasobservedbetween thegroups withrespect to gender, age, height, weight, ASA physical status, and duration of the operation (Table 1). The maximum sen-soryblock level reached toS1 dermatome in both of the groups. The median upper limit of the sensory block was S2in Group II and S1 in Group I preoperatively. Time to reachS4dermatomewassimilarbetweenthegroups. Pre-operativeandpostoperativemaximumblockeddermatomes inboth ofthe groups aregivenin Table2.Mean times to

Table1 Patientcharacteristics,operationtime,typeofsurgicalprocedure.

GroupI(n=26) GroupII(n=26) p

Age(years) 24±8 30±10 0.061

Height(cm) 173_±8 175_±8 0.94

Weight(kg) 81±17 82±14 0.346

Gender(female/male) 3/23 4/22 0.687

Durationofsurgery(min) 21±7 36±12 0.233

Surgicalprocedure(n)

Pilonidalsinusexcision 22 21 0.021

Hemorrhoidectomy 2 3

Analfissure 2 2

Dataareexpressedasmeanvalues_±SD.

Table2 Spinalblockcharacteristics,timetofirstvoidingofurine,analgesicrequirementandpatientsatisfaction. GroupI(n=26)

Median(range)

GroupII(n=26) Median(range)

pvalue

TimetoreachS4blockade(min) 3(2---5) 3(3---5) 0.821

Preoperativemaximumblockeddermatome S2(S1---S3) S1(S1---S3) 0.014 Postoperativemaximumblockeddermatome S2(S1---S3) S1(S1---S2) 0.408

2-Segmentregressiontime(min) 25(20---40) 35(30---75) p<0.001

Timetofirstanalgesicrequirement(min) 180(60---240) 250(15---340) p<0.001

Timetofirstvoid(min) 192(120---292) 240(105---420) 0.085

Patientsatisfaction,n(%)

1=perfect 20(76.9) 22(84.6)

2=satisfactory 6(23.1) 4(15.4)

3=poor 0 0

4=worst 0 0

two-segmentregressionwereshorteringroupIthangroup II(p<0.001). Allpatientsin both ofthegroups wereable topositionthemselveswithBromagescores0.Timeto void-ingwassimilarinbothofthegroups(p=0.085),andnoneof thepatientsneededcatheterization.Firstanalgesic require-ment timewasshorter in group Icompared withgroup II (p<0.001).Noneofthepatientsneededsupplemental anal-gesicduringtheoperation.Patientssatisfactionweresimilar inbothofthegroups, and76.9%ofthepatientsingroupI and84%ofthepatientsingroupIIassessedtheanesthetic qualityas ‘perfect’ (Table 2).The adverse effects during theintraoperativeandpostoperativeperiod;nausea vomi-ting andpruritus were similarin both of thegroups. One patientingroupIandfivepatientsingroupIIreceived treat-mentforthepruritus(p=0.086).Therewerenosignificant differences between the groups regarding mean arterial bloodpressureandheartratevalues,beforeandduringthe surgery.

Discussion

Levobupivacaine,thepureS(-)-enantiomerofbupivacaine, wasdemonstrated lessaffinityand strengthof depressant effectsonto myocardial and central nervoussystem com-paredwithbupivacaine.Additionally,producingdifferential neuraxialblockpreservingmotorfunctionatlow concentra-tionsprovidesanadvantagetolevobupivacaine.9_Adjuvants

suchas fentanyl and sufentanyl reduce the dose of local anestheticsandprolongthesensoryblockwithoutdelaying timetovoid.The recommended intrathecal dosesof fen-tanylasadjuvanttolocalanestheticsis10---25␮g.10,11 _Also

theseadjuvantsimprovetolerancetovisceralsensationslike bladder distensionand peritoneal stretch. However adju-vantssuchasfentanyltolocalanestheticsdoesnotprolong thedurationofmotorblockade.10,11_{So,twodifferentdoses}

offentanylcombinedwithlow-doselevobupivacainewere usedinthisstudy.Bothoftheanestheticcombinations pro-videdgoodqualityofspinalanesthesiawithoutmotorblock. Cuvas etal.5 _{compared 5mg0.5% plainbupivacaine in}

1mLvolumewith5mg0.5%plainlevobupivacaine in1mL volumefor pilonidal cyst/sinussurgery in the prone posi-tion.Theyfoundsimilarresultswithregardtosensoryand motor blockade in both of the groups. The median maxi-mumlevelofsensoryblock reachedtoT10dermatome in thelevobupivacainegroup.Allthepatientsinthe levobupi-vacainegrouphad motorblockade equivalenttoBromage score1or2.Patientsatisfactionwas92%inthe levobupi-vacainegroup. Inthe present study,we used2.5mg dose ofhyperbaric levobupivacainewithtwodifferentdosesof fentanyl.Wealsofoundsimilarresultsforthetimeofonset ofthesensoryblockinthetwogroupsandmotorblockwas notobservedinanyofthepatients.Weusedsmalldoseof levobupivacainethan Cuvas etal.usedin their studyand maximumsensoryblock waslimitedtotheS1dermatome inbothofthegroups.Thesensoryblocklevelwassufficient for anorectal surgeryand allthe patients expressedtheir anestheticsatisfactionasgoodorverygood.

Erbay et al.12 _{compared the effects of spinal}

anes-thesia provided by 7.5mg hyperbaric bupivacaine plus 25␮gfentanylwith7.5mghyperbariclevobupivacaineplus 25␮g fentanyl for transurethral surgery. They found that

hyperbaric levobupivacaineplus25␮gfentanylprovideda shorter motorblock timeandalonger sensoryblocktime than7.5mghyperbaricbupivacaineplus25␮gfentanyl.In another study, Girgin et al.13 _{suggested that intrathecal}

administrationof25␮gfentanyladdedto5mg levobupiva-caine0.5%foringuinalherniorrhaphyincreasedthequality ofspinalanesthesiaandallowedtouseasub-anesthetic lev-obupivacainedose.Inthepresentstudy,levobupivacainein combination with25␮gfentanyl providedasensory block withlonger duration than the hyperbaric levobupivacaine in combination with 12.5␮g fentanyl. Also first analgesic requirementtimewassignificantlylongerinthespinal anes-thesia group provided by hyperbaric levobupivacaine plus 25␮gfentanyl.Assimilartoother studies,combining fen-tanylwithlevobupivacaineprolongedsensoryblockwithout affectingmotorrecoveryortimetovoid.10,11

Hyperbariclocalanestheticsolutionshaveahigher den-sity compared with CSF. Forthis reason, hyperbaric local anesthetic solutionstend tomove inacephaled direction andmayproducemotorblockadeintheanteriorrootsofthe thoracicregionintheproneposition.6,7_{Ithasbeenshown}

that usingsmall dosesof local anesthetics withadequate basicityandappropriatepatientpositioning,onlythenerve roots supplying a specific area is affected.6,7 _Also

admin-istrationof localanesthetics withahigh speedaffectsits distributionoflevobupivacainetothevertexpositioninthe thecal cavity and causes hemodynamic changes.14 _{In this}

studyweusedhyperbaricsolutionsoflevobupivacaineand measuredthedensitiesofthesolutionsat37◦C.Local anes-thetics were administered at a rateof 1mL/60s in order tominimizethedistributionofhyperbariclevobupivacaine dependingontheconversionofpatientposturefromsitting positiontoproneposition.Motorblockadewasnotobserved inbothofthestudygroups.Noclinicallysignificant hemo-dynamicchangessuchasbradycardiaortreatmentrequiring hypotensionoccurredinanyofthepatients.

The minimal recommended dose of spinal hyperbaric bupivacaineis4---5mgforanorectalsurgery.15_.Gurbetetal.3

compared 5mg 0.5% spinal hyperbaric bupivacaine and 2.5mg 0.5%hyperbaric bupivacaine plus 25␮gfentanyl in outpatientanorectal surgery. They found that addition of 25␮g fentanyl to 2.5mg 0.5% bupivacaine prolonged the duration of sensory blockade and reduced postoperative analgesic requirement. Upper limit of the sensory block reached to T9 (T4-L1) dermatome and median maximum motor blockade score was 21---3 _{in hyperbaric bupivacaine}

plusfentanylgroup.Weused2.5mgofhyperbaric levobupi-vacaine0.5%withtwodifferentfentanylcombinationsfor spinal anesthesia in anorectal surgery. The median upper limit of thesensoryblock wasS1in the spinalanesthesia group provided by hyperbaric levobupivacaine plus 25␮g fentanyl.MediantimetoS4sensoryblockadewas3minand motorblockadewasnotobservedintheanyofthepatients. Bradycardia or hypotension was not observed during the surgery.Wesuggestthat2.5mghyperbariclevobupivacaine with25␮gfentanylcanbepreferredforspinalanesthesiain anorectalsurgerywithhighriskpatientsbecauseofbetter hemodynamicstabilityandwithoutdelayininitiationofthe surgery.

Wassefetal.16 _{investigatedtheefficacyof1.5mg}

bupi-vacaineinshortperianalprocedureswiththedoseof6mg which was regularly used in spinal saddle block. They

concluded that spinal perianal block produced by 1.5mg bupivacaineprovidedasignificantlyrestrictedsensoryblock levels (median maximum=S4), and motor block was not observedinanyofthepatientinthisgroupcomparedwith the groupwhich was6mg bupivacaine used.Alsotimeto ambulationandvoidingwereshorterinthelowdose bupi-vacainegroup.Theyconcludedthat,maintainingtheseated positionisessentialforrestrictionofblockadetothemost caudalspinalnerverootswhichsupplytheperianalarea.15

Inanotherstudy,Kazaketal.comparedtheefficacyofspinal 1.5mghyperbariclevobupivacainewith6mghyperbaric lev-obupivacaineforanalsurgery.Sensoryblockwaslimitedto S4dermatomeintheperianalblockgroupprovidedby1.5mg hyperbaric levobupivacaine.They stated that1.5mgdose of intathecal hyperbariclevobupivacaine providedshorter duration andfaster regression of sensoryblock compared with 6mg hyperbaric levobupivacaine.4 _{Kazak et al. kept}

thepatientsinthesittingpositionatleast20mininorder toconfinethesmallbolus oflevobupivacainetothelower endoftheduralsac.Asdifferentfromthestudyperformed byKazaketal.,inthepresentstudy,thepatientswerekept in the sitting positionfor 5min. The S4sensory blockade wasachievedin3minandmaximumblockedsensorylevel reachedtoS1level,soitcanbesaidthattherewasnodelay inreadinessforsurgery.

Inconclusion,wefoundthatthetworegimensprovided goodqualityspinalanesthesiainanorectalsurgerywithout affecting the motor functions and hemodynamic stability. Howeverthe additionof 25␮fentanyl increased duration ofsensoryanalgesiawithlongerfirstanalgesicrequirement time without prolonging time to void or intensifying the motorblockade.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

References

1.MaroofM,KhanRM,SiddiqueM,etal.Hypobaricspinal anasthe-sia(0.1%)givesselectivesensoryblockforano-rectalsurgery. CanJAnaesth.1995;42:691---4.

2.Burlacu CL,Buggy DJ.Updateonlocalanesthetics: focuson levobupivacaine.TherClinRiskManage.2008;4:381---92.

3.GurbetA,TurkerG,GirginNK,etal.Combinationofultra-low dose bupivacaineand fentanyl for spinal anaesthesiain out-patientanorectalsurgery.JIntMedRes.2008;36:964---70.

4.KazakZ,EkmekciP,KazbekK.Hyperbariclevobupivacainein analsurgery.Anesthetist.2010;59:709---13.

5.Cuvas O, GulecH, KaraaslanM, et al. The useof low dose plainsolutionsoflocalanaestheticagentsforspinalanaesthesia intheproneposition:bupivacainecomparedwith levobupiva-caine.Anaesthesia.2009;64:14---8.

6.Gouveia MA, Imbelloni LE. Understanding spinal anesthesia. ActaAnaesthesiolScand.2006;50:260.

7.Povey HM,Jacobsen J, Westergaard-Nielsen J. Subarachnoid analgesiawithhyperbaric0.5%bupivacaine:effectofa60-min periodofsitting.ActaAnaesthesiolScand.1989;33:295---7.

8.Goel S, Bhardwaj N, Grover VK. Intrathecal fentanyl added tointrathecalbupivacainefordaycasesurgery:arandomized study.EurJAnaesthesiol.2003;20:294---7.

9.CamorciaM,CapognaG,BerrittaC,etal.Therelativepotencies formotorblockafterintrathecalropivacaine,levobupivacaine, andbupivacaine.AnesthAnalg.2007;104:904---7.

10.HuntCO,NaultyJS,BaderAM,etal.Perioperativeanalgesia withsubarachnoidfentanyl-bupivacaineforcesareandelivery. Anesthesiology.1989;71:535---40.

11.Akerman B,Arweström E,Post C.Localanesthetics potenti-atespinal morphineantinociception. AnesthAnalg. 1988;67: 943---8.

12.ErBay RH, Ermumcu O, Hancı V, et al. A comparison of spinalanesthesiawithlow-dosehyperbariclevobupivacaineand hyperbaricbupivacainefortransurethralsurgery:arandomized controlledtrial.MinervaAnestesiol.2010;76:992---1001.

13.GirginNK,GurbetA,TurkerG,etal.Thecombinationof low-dose levobupivacaine and fentanyl for spinal anaesthesia in ambulatory inguinal herniorrhaphy. J Int Med Res. 2008;36: 1287---92.

14.Simon L, Boulay G, Ziane AF, et al. Effect ofinjection rate onhypotensionassociatedwithspinalanesthesiaforcesarean section.IntJObes.2000;9:10---4.

15.GudaityteJ, MarhertieneI,Pavalkis D,etal. Minimal effec-tivedoseofspinalhyperbaricbupivacaineforadultanorectal surgery:adoubleblind,randomizedstudy.Medicine(Kaunas). 2005;41:675---84.

16.WassefMR,MichaelsEI,RangelJM,etal.Spinalperianalblock:a prospective,randomized,double-blindcomparisonwithspinal saddleblock.AnesthAnalg.2007;104:1594---6.