REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologiawww.sba.com.br
SCIENTIFIC
ARTICLE
Evaluation
of
spinal
anesthesia
blockade
time
with
0.5%
hyperbaric
bupivacaine,
with
or
without
sufentanil,
in
chronic
opioid
users:
a
randomized
clinical
trial
Mostafa
Sadeghi,
Reza
Atef
Yekta,
Omid
Azimaraghi,
Gilda
Barzin,
Ali
Movafegh
∗DepartmentofAnesthesiology,PainandCriticalCare,Dr.AliShariatiHospital,TehranUniversityofMedicalSciences,Tehran,Iran
Received22August2014;accepted11November2014 Availableonline21October2015
KEYWORDS
Spinalanesthesia;
Chronicopioiduse;
Bupivacaine; Sufentanil
Abstract
Objective:Theprimaryoutcomeofthisstudywastoevaluatetheeffectofaddingsufentanilto hyperbaricbupivacaineondurationofsensoryblockadeofspinalanesthesiainchronicopioid usersincomparisonwithnon-addicts.
Methods:Sixtypatients scheduledfororthopedicsurgeryunderspinalanesthesiawere allo-catedintofourgroups:group1(nohistoryofopiumusewhoreceivedintrathecalhyperbaric bupivacainealongwith1mLsalineasplacebo);group2(nohistoryofopiumusewhoreceived intrathecalbupivacainealongwith1mLsufentanil[5g]);group3(positivehistoryofopiumuse
whoreceivedintrathecalbupivacainealongwith1mLsalineasplacebo)andgroup4(positive historyofopiumusewhoreceivedintrathecalbupivacainealongwith1mLsufentanil[5g]).
Theonsettimeanddurationofsensoryandmotorblockadeweremeasured.
Results:Thedurationofsensoryblockadeingroup3was120±23.1minwhichwassignificantly lessthanothergroups(G1=148±28.7,G2=144±26.4,G4=139±24.7,p=0.007).Theduration ofmotorblockadeingroup3was145±30.0minwhichwassignificantlylessthanothergroups (G1=164±36.0,G2=174±26.8,G4=174±24.9,p=0.03).
Conclusions:Additionof5gintrathecalsufentaniltohyperbaricbupivacaineinchronicopioid
userslengthened thesensoryand motordurationofblockade tobeequivalent toblockade measuredinnon-addicts.
© 2015 Sociedade Brasileira de Anestesiologia. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
∗Correspondingauthor.
E-mail:movafegh@sina.tums.ac.ir(A.Movafegh).
http://dx.doi.org/10.1016/j.bjane.2014.11.009
PALAVRAS-CHAVE
Raquianestesia;
Usocrônicode
opioides; Bupivacaína; Sufentanil
Avaliac¸ãodotempodebloqueiodaraquianestesiacombupivacaínaahiperbárica
0,5%,comousemsufentanil,emusuárioscrônicosdeopioides:umestudoclínico
randômico
Resumo
Objetivo: Avaliaroefeito daadic¸ãode sufentanilàbupivacaínahiperbárica nadurac¸ãodo bloqueiosensorialdaraquianestesiaemusuárioscrônicosdeopioidesemcomparac¸ãocomnão adictos.
Métodos: Foramdistribuídosemquatrogrupos60pacientesagendadosparacirurgiaortopédica sob raquianestesia:Grupo 1 (semhistória deuso deópio, recebeubupivacaína hiperbárica intratecaljuntamentecom1mLdesoluc¸ãosalinacomoplacebo);Grupo2(semhistóriadeuso deópio,recebeubupivacaínaintratecaljuntamentecom1mLdesufentanil[5g]);Grupo3
(comhistóriadeusodeópio,recebeubupivacaínaintratecaljuntamentecom1mLdesoluc¸ão salinacomoplacebo)eGrupo4(Comhistóriadeusodeópio,recebeubupivacaínaintratecal juntamentecom1mLdesufentanil[5g]).Otempodeinícioeadurac¸ãodosbloqueiossensitivo
emotorforamregistrados.
Resultados: A durac¸ãodo bloqueio sensorialno Grupo 3foi de 120 ±23,1min, um tempo significativamentemenorquenosoutrosgrupos(G1=148±28,7,G2=144±26,4,G4=139
±24,7,p=0,007).Adurac¸ãodobloqueiomotornoGrupo3foide145±30,0min,umtempo significativamentemenorquenosoutrosgrupos(G1=164±36.0,G2=174±26.8,G4=174±
24,9;p=0,03).
Conclusões: Aadic¸ãode5g desufentanilintratecalàbupivacaínahiperbáricaemusuários
crônicosdeopioidesaumentadoadurac¸ãodosbloqueiossensorialemotordeformaequivalente aobloqueioavaliadoemnãoadictos.
© 2015 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. Este é um artigo Open Access sob a licença de CC BY-NC-ND (http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Introduction
Motor vehicle trauma may result in lower limb fractures requiring operative intervention, and may occur in the setting of opium abuse.Since spinal anesthesia is a pop-ular anesthetic technique in lower limb surgeries,1,2 the characteristics of spinal anesthesiain this population are important.
In the studied geographical region, Iran, determining a definite estimate of prevalence and incidence of sub-stance abuse is not possible due to social stigmatization alongwithlegalrestrictions.Betweendifferentsubstances, most commonly, opioids are abused and inhalation the most frequent route of abuse.3 Furthermore, many of the victims of motor vehicle accidents are chronic opi-oidusersandtheaccidentsaretheresultof driver’sdrug abuse.4
The sensory and motor blockade behavior of spinal anesthesiainlong-term chronic opioidusers hasnotbeen previouslystudiedthoroughly.
InastudyconductedbyDabbaghetal.,durationofspinal anesthesia with hyperbaric bupivacaine in chronic opium abusersundergoinglowerextremityorthopedicsurgerywas studied.Itwasshownthatthedurationofsensoryblockwas muchshorterinchronicopiumabuserscomparedwith non-abusers.5Thehypothesisofourstudywasthattheduration ofspinalanesthesiainchronicopioidusersisshorter than non-addict patients andadding intrathecal sufentanil can increasespinalanesthesiablockadetimeinchronic opioid user.
Theprimaryoutcomeof thisstudywastoevaluatethe effectof adding sufentanil tointrathecal bupivacaine on durationofsensoryandmotorblockadeofspinal anesthe-siachronic opioid userscompared tonon-addictpatients. The onsetof sensory and motor blockadewas considered secondaryoutcomes.
Materials
and
methods
ThestudyprotocolwasapprovedbytheInstitutionalEthics Committeeof Tehran University of Medical Sciences, and afterathoroughdetailedexplanationofthenatureofthe studytotheparticipants,aninformed,writtenconsentwas obtainedfromallthepatients.
SixtyAmericanSocietyofAnesthesiologistphysicalstatus (ASA)classIandII,maleandcurrentsmokerpatients,aged between18and60,whowerescheduledforelectivelower limborthopedicsurgeryunderspinalanesthesia(lastingless than2h)wereenrolledinthisrandomized,double-blinded clinicaltrial. Patientswithany contraindicationstospinal anesthesia,patientswithaddictiontoanysubstanceother thanopiumandcigarettes,andpatientswithhistoryof car-diac,respiratory,orpsychologicaldiseasewerenotentered in the study. It had been considered that in instances of failedspinal anesthesiaor when surgerytook longerthan twohoursnewpatientswerereplacedinthestudy.
theanesthesiologistandthepatientswereblindedtogroup assignment.The anesthesiologist whoperformed the sub-arachnoid block and documented the sensory levels was blindedtothepatient’sgroup.On arrivaltotheoperating room,basedonapreviouslygeneratedcomputer randomiza-tionlist,patientswereassignedintogroups.Group1(n=15) hadnohistoryofchronicopiumuseandreceivedintrathecal hyperbaricbupivacainealong with1mLsalineasplacebo. Group2(n=15)hadnohistoryof opiumuseandreceived intrathecalhyperbaric bupivacaine alongwith1mL sufen-tanil(5g;n=15). Group3 (n=15)had a positivehistory of chronic opium useand received intrathecal hyperbaric bupivacainealongwith1mLsalineasplacebo.Lastly,group 4(n=15) hada positive historyof chronic opium useand receivedintrathecalhyperbaricbupivacainealongwith1mL sufentanil(5g).The bupivacaine ampoules (20mg/4mL) contained320mgglucosemonohydrate.
Chronicopiumusewasdefinedasrecurrentand continu-ousdailyconsumptionof1---2gofopiumviainhalationroute for at leastone year withouta cessationuntil theday of surgerybasedonthehistoriesthatreportedbythepatients. Patients with poly substance abuse were not enrolled in thestudy.None of the patientshad anyintention tostop opiumusebeforesurgeryandallthepatientswereadvised tocontinueusingtheirtypicalinhaledopiumuntilthedayof surgeryinthepreoperativevisit.Patientsweregiventheir dailydosesofinhaledopiumonthedayofsurgery.Inorderto ruleoutopiumuseinthecontrolgroupsandconfirmopium useinthestudygroup,inallpatients,anopiateurinetest wasperformed.
Pre-operativepainmanagementprotocolwasthesame for all the patients. The patients received intermittent (every 6h) intravenous apotel (15mg/kg) (Intravenous Paracetamol1000mg/6.7mL,UNI-PHARMAS.A.) iftheVAS scoreforpainwashigherthan3.Diclofenacsuppositorywas administeredtopatientswhohadpaindespiteintravenous apoteladministration.
Two hours before surgery, patients received 1mg oral lorazepamas premedication. On arrival in the operating room,standardmonitoringwasestablished (electrocardiog-raphy,noninvasivebloodpressure,pulseoximetryandheart rate)andoxygenwasdeliveredvia aventurefacemask at arateof3L/min.An18-gaugecannulawasinsertedintoa veinonthedorsumofthenon-dominanthandandabolus doseoflactatedringersolution7mL/kgwasadministered. Then,withthepatient inthe lateraldecubitus positiona dusinganaseptictechnique,a25-gaugepencilpointneedle wasinserted intrathecallyviaa midlineapproachintothe L3---L4orL4---L5interspaces.
Patientsingroups1and3receivedintrathecally3mLof 0.5%hyperbaricbupivacainealongwith1mLsaline.Patients ingroups2and4wereadministered3mLof0.5%hyperbaric bupivacaineand1mL(5g)ofsufentanil.Allthesolutions wereadministered at a rate of 2mL/s. All patients were placedinsupinepositionfollowingdruginjection.Torecord the onsettime and durationof sensoryand motor block, sensorylevelwasassessedusingapinpricktesteveryminute for10minandthenevery10minfor120minaftertheendof injection(zerotime).Themotorblockadewasassessedby theBromageScale(GradeI:freemovementofthelegsand feet,GradeII:justabletoflexkneeswithfreemovementof feet,GradeIII:unabletoflexknees,butwithfreemovement
offeet,GradeIV:unabletomovelegsorfeet).6Theonset timeofsensoryblockadewasdefinedasthetimefromdrug administrationuntilbilateral T8levelof sensoryblockade wasachieved.Thedurationofsensoryblockwasconsidered asthetimefromthehighestlevelofsensoryblockadeuntil 4segmentregressionswereobserved.7
The onset time of motor blockade wasdefined as the timefromdruginjectionuntilagradeIVBromagescorewas achieved.The durationof motor block wasconsidered as thetimefromfullintensitymotorblockadeuntilaBromage gradeIscorewasdocumented.
Ifany of the patients complained of pain at any time during the operation, this was considered to be a failed spinalanesthesia,andgeneralanesthesiawastheninduced immediately.
Hypotensionwasdefinedasadecreaseinsystolicblood pressure to less than 90mmHg or 25% less than base-line. Hypotension was treated with bolus doses of 10mg intravenousephedrine.Bradycardia(HR<50beat/min)was treatedby0.5mgIVatropine.Incasesofnauseaor vomit-ingwithoutthepresenceofbradycardia,patientsreceived 10mgIVmetoclopramide.
Itwasdeterminedthatasamplesizeof15participantsin eachgroupwouldbesufficienttodetecta30mindifference insensoryblocktime,estimatinganSDof28min,apower of80%,andasignificancelevelof5%.
StatisticalanalysisofthedatawasperformedusingSPSS for windows, release 17.5 (SPSS.Inc). The distribution of data was evaluated using the Kolmogorov---Smirnov test. Age, weight, height, and duration of surgery followed a normal distribution and were analyzed by using one-way analysis of variance (ANOVA) and Tukey post hoc tests. However, sensory and motor onset time and duration of blockadesdidnotfollownormaldistribution.Their compar-isonswereperformedusingMann---Whitneytest.Twotailed p-values<0.05wereconsideredstatisticallysignificant.
Results
Sixtymalepatientswererandomized.Therewereno proto-colviolationsandallpatientswereincludedintheanalysis. The basic characteristics of theparticipants, including age, weight, height, the duration of the surgery and the durationofanesthesiaweresimilaringroupsandare pre-sented in Table 1.Differenttypes of orthopedic surgeries performed in each group arepresented in Table 2. There werenostatisticaldifferencesbetweenthe typesof surg-eriesingroups.Thehighestlevelofsensoryblockadeineach groupispresentedinTable3.Urinaryopiumtestwas posi-tiveinallthepatientsingroups3and4andwasnegativein allpatientsingroups1and2.
Table1 Demographicdataofthepatientsanddurationofsurgery. Group1
(n=15)
Group2 (n=15)
Group3 (n=15)
Group4 (n=15) Age(years)a 34.4±10.8 35.7±8.3 40.3±9.3 36.8±5.8
Weight(kg)a 74.4±13.2 70.0±15.4 73.6±8.4 73.6±14.3
Height(cm)a 174.4±10.2 174.2±8.5 172.6±6.3 171.4±8.9
Durationofsurgery(min)a 110±28.9 99.3±22.9 91.3±30.3 97.3±30.7 a Therewasnosignificantdifferenceingroups.
Table2 Typesofsurgeries. Group1 (n=15)
Group2 (n=15)
Group3 (n=15)
Group4 (n=15) Femoralfracture 4 5 4 7 Anklefracture 6 7 5 5 Tibia/fibula
fracture
5 3 6 3
Table3 Highest levelofsensoryblock achievedineach group.
Group1 (n=15)
Group2 (n=15)
Group3 (n=15)
Group4 (n=15) 6ththoraciclevel 5 4 5 5 7ththoraciclevel 6 7 5 6 8ththoraciclevel 4 4 5 4
The duration of sensory blockade was significantly
dif-ferent between groups. The duration of motor blockade
in group 3 (145±30.0min) which was significantly less
thangroup1(164±36.0min),group2(174±26.8min)and
group4(174±24.9min)(one-wayanalysisofvariancetest,
p=0.007). There wasnostatistical difference in duration
ofsensoryandmotorblockadebetweengroups 1,2and4
(Tukeyposthoctest)(Table4).
Discussion
The present studyillustrated that thedurationof sensory and motor blockade in spinal anesthesia with intrathe-cal hyperbaric bupivacaine is shorter in chronic opioid users.Interestingly, adding 5gof sufentanil tothe local
anestheticsolution increasedthe duration of sensoryand motorblockadeinchronicopioidusers.
Adding5gofsufentaniltothelocalanestheticsolution hadnoeffectonthedurationofsensoryandmotorblockade innon-addicts.Nodifferenceinsensoryormotorblockade onsettimewasobservedinanyofthegroups.
Few data are available in the literature regarding the behavior of regional anesthesia in chronic opioid users. When a thorough search of the known databases such as ISIandPubMedwasdone,nostudyregardingtheeffectof addingopioidsto localanesthetics in spinal anesthesiain chronicopioiduserswasfound.
Aspreviously mentioned,in astudyconductedby Dab-bagh et al., it was observed that a shorter duration of sensory and motor blockade occurred with intrathecally administrationofbupivacaineinchronicopioiduserswhen compared to non-addicts. It was proposed that a cross-tolerance mayexistbetween local anesthetics andopioid compoundsatthelevelofspinalneurons.5Inanotherstudy conducted by the same team, the effect of intrathecal administrationof lidocaine in spinal anesthesiawas stud-iedinchronicopioiduserswithsimilaroutcomes,including shortersensoryandmotorblockadeduringspinal anesthe-siainchronicopioidusers.8However,theeffectofaddingan opioidcompoundtolocalanestheticsinspinalanesthesiain ordertomodifythisshorteneddurationwasnotexamined byeitherofthesestudies.
Inasurvey,itwasconcludedthatintrathecalsufentanil producesasimilarqualitybutshorterdurationofanalgesia incocaine-abuserparturient.9
Themechanismofmodificationofopioideffectinchronic opioidusersisnotcompletelyclear.Thiseffectmaybe par-tiallyexplainedbythedown-regulationofopioidreceptors ora crosstolerance between opioidsandlocalanesthetic receptors,yetitissofarofftoclearlydescribethepathways whicharealteredor modifiedin chronicopioid users.10---15
Table4 Sensoryandmotorblockadetime,sensoryandmotorduration. Group1
(n=15)
Group2 (n=15)
Group3 (n=15)
Group4 (n=15) Sensoryblockadeonsettimea 2.8±1.7 2.4±0.9 3.4±1.1 2.3±1.4
Motorblockadeonsettimea 5.5±3.0 4.1±1.3 5.8±2.3 5.3±2.3
Durationofsensoryblockade 148±28.7 147±26.4 120±23.1b 139±24.7
Durationofmotorblockade 164±36.0 174±26.8 145±30b 174
±24.9
Consideringthisfactthattherelationbetweenpain percep-tionandsubstanceabuseismulti-factorial,furtherstudyis neededtounderstandingtheunderlyingmechanisms.
Theeffectsofintrathecaladditionofdifferentclassesof opioidstolocalanestheticshavebeenpreviouslystudiedin non-addicts.Theadditionoffentanylandsufentanilto con-tinuousspinalanesthesiaproduceseffectiveanalgesiawith lowadverseeffects,16andintrathecalmeperidineor sufen-tanilgavegoodpostoperativeanalgesiaincesareansection surgery.17---19
There are some limitations in this study. First,due to culturalissuesin Iran,addict womenrarely agreetotake partin suchstudies due tothe stigmatizationthat addic-tion has in Iranian culture.20---22 Consequently, only men participatedinourstudy.Furthermore,thereisapossible statistical concern in our study. The sample size of each group(n=15)maybeinadequatetodetectanydifferences inspinalanesthesiadurationinnon-addictsandopioidusers whounderwentspinalanesthesiawithsufentaniland bupi-vacaine.Additionally,knowingtheexactdailydoseofopium consumptionineachofthepatientsandtheconcentration oftheeffectivealkaloidsintheopiumusedbythepatients wasimpossible.
Inconclusion,thisstudyshowedthatthelengthof sen-soryandmotorblockadeisshorterinchronicopioidusers. Theadditionof5gofintrathecalsufentaniltohyperbaric bupivacainein opiumaddicts lengthenedthe sensoryand motor duration of blockade tobe equivalent toblockade measuredinnon-addicts.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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