RevBrasAnestesiol.2017;67(6):615---618
REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologiawww.sba.com.br
SCIENTIFIC
ARTICLE
Comparison
of
granisetron
and
lidocaine
on
reducing
injection
pain
of
etomidate:
a
controlled
randomized
study
Alireza
Saliminia
a,
Omid
Azimaraghi
a,
Amir
Javadi
b,
Maryam
Abdoulahpoor
b,
Ali
Movafegh
a,∗aTehranUniversityofMedicalSciences,Dr.AliShariatiHospital,DepartmentofAnesthesiologyandCriticalCare,Tehran,Iran bTehranUniversityofMedicalSciences,Dr.AliShariatiHospital,AnesthesiologyResearchDevelopmentCenter,Tehran,Iran
Received6July2015;accepted4April2017
Availableonline27June2017
KEYWORDS
Granisetron; Lidocaine; Etomidate; Pain
Abstract
Backgroundandobjectives: Reducingpain oninjection ofanestheticdrugs is ofimportance toevery anesthesiologist.In thisstudywe pursuedtodefineif pretreatmentbygranisetron reducesthepainoninjectionofetomidatesimilartolidocaine.
Methods:Thirtypatientsagedbetween18and50yearsofAmericanSocietyofAnesthesiologists physicalstatusclassIorII,whomwerecandidatesforelectivelaparoscopiccholecystectomy surgerywereenrolledinthisstudy.Two20gaugecannulaswereinsertedintotheveinsonthe dorsum ofbothhandsand100mLofnormalsalinewasadministered duringa10minperiod fromeachcannula.Usinganelasticbandasatourniquet,venousdrainageofbothhandswas occluded.2mLofgranisetronwasadministeredintoonehandand2mLoflidocaine2%atthe same timeinto theotherhand.One minutelater theelastic bandwas openedand2mLof etomidatewasadministeredtoeachhandwithequalrates.Thepatientswereaskedtogivea scorefrom0to10(0=nopain,10=severepain)toeachthepainsensedineachhand. Results:Twopatientsweredeeplysedatedafterinjectionofetomidateandunabletoanswer anyquestions.Themeannumericalratingscoreforinjectionpainofintravenouslyadministered etomidateafterintravenousgranisetronwas2.3±1.7,whichwaslowerwhencomparedwith painsensedduetointravenouslyadministeredetomidateafteradministrationoflidocaine2% (4.6±1.8),p<0.05.
Conclusion: Theresultofthisstudydemonstratedthat,granisetronreducespainoninjection ofetomidatemoreefficientlythanlidocaine.
©2017PublishedbyElsevierEditoraLtda.onbehalfofSociedadeBrasileiradeAnestesiologia. ThisisanopenaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
∗Correspondingauthor.
E-mail:[email protected](A.Movafegh).
http://dx.doi.org/10.1016/j.bjane.2017.04.001
616 A.Saliminiaetal.
PALAVRAS-CHAVE
Granisetrona; Lidocaína; Etomidato; Dor
Comparac¸ãodegranisetronaelidocaínanareduc¸ãodadorcausadapelainjec¸ão
deetomidato:estudorandômicoecontrolado
Resumo
Justificativaeobjetivos: A reduc¸ão da dor causada pela injec¸ão de anestésicos é impor-tanteparatodososanestesiologistas.Nesteestudobuscamosdefinirseopré-tratamentocom granisetronareduzadorcausadapelainjec¸ãodeetomidatodeformasemelhanteàlidocaína. Métodos: Trintapacientescomidadesentre18e50anos,estadofísicoASAIouII(deacordocom aclassificac¸ãodaSociedadeAmericanadeAnestesiologistas) ecandidatos àcolecistectomia laparoscópicaeletivaforamincluídosnesteestudo.Duascânulasdecalibre20foraminseridas nasveiasdodorsodeambasasmãose100mLdesorofisiológicoforamadministradosdurante 10 minutosatravés decadacânula. Usandoum torniquete elástico, adrenagem venosade ambasasmãosfoiocluída.Granisetrona(2mL)foiadministradoemumadasmãoselidocaína a2%(2mL)naoutramãoaomesmotempo.Apósumminuto,otorniquetefoiliberadoe2mL deetomidatoforamadministradosemvelocidadeigualacadaumadasmãos.Solicitamosdos pacientesumaclassificac¸ãode0a10paraadorsentidaemcadaumadasmãos(0=semdor, 10=dorintensa).
Resultados: Doispacientesestavamprofundamentesedadosapósainjec¸ãodeetomidatoe, portanto,incapazesderesponderaqualquerpergunta.Oescoremédiodeclassificac¸ãodador àinjec¸ãodeetomidatoadministradoporviaendovenosaapósgranisetronaintravenosafoide 2,3±1,7,oquefoimenoremcomparac¸ãocomadorsentidaàadministrac¸ãointravenosade etomidatoapósaadministrac¸ãodelidocaínaa2%(4,6±1,8),p<0,05.
Conclusão:Oresultado desteestudodemonstrouquegranisetronareduzadorcausada pela injec¸ãodeetomidatocommaiseficáciaquelidocaína.
©2017PublicadoporElsevierEditoraLtda.emnomedeSociedadeBrasileiradeAnestesiologia. Este ´e um artigo Open Access sobuma licenc¸a CC BY-NC-ND(http://creativecommons.org/ licenses/by-nc-nd/4.0/).
Introduction
Etomidate is an almost popular intravenous anesthetic agent,with almost uniquehemodynamic profile following IVadministrationofit,asusuallythereisnohemodynamic change,soetomidatewasconsideredforthermodynamically unstable patients. Etomidate is formulated in propylene-glycol therefore following intravenous injection, it may producedamagesinvascularendotheliumandsoproduces pain.1Consideringtheimportanceofusingetomidateto
pro-duceasmoothinductionofgeneralanesthesiawithoutany significant hemodynamic change, especially in cases with cardiovasculardisordersorheadtrauma,preventionofpain oninjectionofetomidateseemstobelogical.
Toachievethisgoal,manypretreatmentbyvariousdrugs suchaslidocaine,dexamethasoneandmagnesiumsulphate weretested.2,3Lidocainesignificantlyreducestheincidence
andseverityofpainoninjectionofanestheticdrugs.4
GranisetronisaselectiveinhibitorofType3serotonergic (5-HT3)receptorsthathasbeenusedasanantiemeticand antinausiantforcancerchemotherapypatients.The broad distributionof five hydroxyl-tryptamine (5-HT3)receptors inhuman bodyhas providedthe basisfor investigation of granisetron,asaselectiveserotonin5-HT3receptor antago-nistinnovelapplications.Serotonergicreceptorantagonists havebeenusedtodecreasepainoninjectionofsome anes-theticagentwithvariableresults.5---7Probablyinhibitionof
Type3serotonergicreceptorscanreducethepainon injec-tionofintravenouslyadministereddrugs.
Inpresentstudy,itwashypnotizedthatgranisetroncan reduce painoninjectionof IVetomidate similarandeven morethanlidocaine.
TheeffectofpretreatmentbyIVgranisetrononpainof inductionofetomidatewasconsideredasprimaryoutcome.
Methods
This trial wasreviewed andapproved by the Institutional EthicsCommitteeofTehran UniversityofMedicalSciences and was registered at Iranian registry of clinical trial (IRCT201411025175N19). Aninformedwrittenconsentwas obtainedfromalltheparticipants.
Comparisonofgranisetronandlidocaineonreducinginjection 617
for pain(0=nopain,10=severe pain).Nopremeditations wereadministered.
Onarrivaltotheoperatingroom,allpatientswere mon-itored withan Electrocardiogram(ECG) noninvasiveblood pressureandpulse-oximetry.
Two 20gauge cannulaswereinserted intotheveinson thedorsumofbothhandsand100mLofnormalsalinewas administered during a 10min period from each cannula. Using anelasticband asa tourniquet,venous drainageof bothhandswasoccluded.Twoanesthesiologists,whomdid notratethepainscores,andwherenotawareofthedrug solutions stood on each sides of the patients. An anes-thetist who was not involved in the study prepared drug solutions. 2mL of granisetron was administered into one hand and2mL of lidocaine2%into theother hand at the sametime.Oneminutelatertheelasticbandwasopened and2mLofetomidatewasadministeredtoeachhandwith equal rates at the same time. The patients were asked togivea scoreby thethird anesthesiologist from0to 10 (0=no pain, 10=severe pain) to the pain sensed in each hand.
The choice for the technique used for induction of anesthesiawasleftfor thepatient’s anesthesiologist.The patientsaswellastheanesthesiologistwereunawareofthe natureoftheinterventiondrugs,thus,boththe anesthesi-ologist andthe patients were blinded topatients groups. Arbitrarily,wecodedthedrugsasAB(AforlefthandandB forrighthand)orBA(BforlefthandandAforrighthand). Using a randomly generated computer code, 32 patients wereallocatedtoreceive ABorBAin 4blocksof6and 2 blocksof4.
Basedonpreviousworksandpairedstudydesign,30pairs ofhandwouldbesufficienttodetect50%reductionin per-centageofNRSconsidering twosided˛=0.05,80%power,
and10%dropout.Itwasestimatedthatasamplesizeof30 patients wouldbe sufficienttocomparisona reductionof painscoreoninjection ofetomidate betweengranisetron andlidocaine.
StatisticalanalysisofdatawasperformedusingSPSSfor windows,released17.5.Theintensityofpainwasanalyzed bypairedttest;p<0.05wasconsideredsignificant.
DatawereanalyzedwithSoftwarePackagefortheSocial Sciences(SPSS,version17.5).Normalityofdatawaschecked asneeded.Pairedt-testwasusedtocompareNRSbetween rightandlefthandsandMcNemar---BowkerTestwasusedto comparecategorizedNRSbetweentwohands.
Results
A total of 32 patients were enrolled in the study. Two patientsweredeeplysedatedafterinjectionof etomidate and unable to answer any question. The data about the patientsandsurgeryareinTable1.
The mean NRS for injection pain of intravenously administeredetomidate afterintravenous granisetronwas 2.3±1.7,whichwaslowerwhencomparedwithpainsensed duetointravenouslyadministeredetomidateafter admin-istrationoflidocaine(4.6±1.8),p<0.05.This statistically significantdifferencewasstillobserved,whenpatientswere stratifiedaccordingtogender.
Table1 Demographicdataofthepatients.
Age(years) 34.5±10.1
Sex(F/M) 15/15
Weight(kg) 79.3±11.2
Height(cm) 173.4±8.2
ASA(I/II) 18/12
Durationofsurgery(min) 108±28.9
Datapresentedasmean±SD.
Discussion
Inthisstudytheeffectof granisetronandlidocaine2% on reducingthepainoninjectionofetomidatewascompared. Itwasobservedthatadministrationofgranisetronpriorto etomidatereducespainoninjectionofetomidatemore effi-cientlythanlidocaine.
Fornearlyadecadethecurrentteamofauthorshasbeen workingontheeffectofpretreatmentof variousdrugs on painoninjectionofintravenousdrugs.Awiderangeofdrugs suchasdexamethasone, metoclopramide, ephedrinehave beentestedwithdifferentresults.8---10 Dexamethasoneand
metoclopramidepretreatmentswereshowntobeeffective inreducingtheseverityofpainoninjectionofdiazepam. It was demonstrated that small doses of ephedrine also showedpromising resultsin attenuatingthepainof injec-tion. The fact that 5-HT3 receptors are located in the peripheral and central nervous system was the rational for using ondansetron for the previous study and to pur-suemore studies onthe actual effects of 5-HT3receptor antagonists.5-HT3 receptorantagonists alsopossess anti-nociceptiveproperties,sotheycandecreasepaininasimilar waytolocal anesthetics.In an earlierstudyit wasshown that ondansetron reduces pain oninjection of etomidate effectively11 whichwascongruentwiththehypothesisthat
5-HT3receptorantagonistsaretheneartopreciseclassof drugsforreducingpainoninjection.
Granisetron is a specific 5-HT3 receptor antagonist thatabolishes allodyniaand hyperalgesia.12,13 Granisetron
can treat emesis induced by chemotherapy and it seems this effect is equivalent to, or better than, that of ondansetron.14
Otherstudies have alsobeenundertakenwiththegoal ofreducingpainoninjectionofanestheticdrugs.Recently, granisetronhasbeenshowntobemoreefficientin attenu-atingpainoninjectionofpropofolcomparedtomagnesium sulfateandnitroglycerine.15Themechanismofgranisetron
inreducingpainoninjectionofpropofolisnotcompletely known,lidocaineisaperipherallocalanestheticthat atten-uates the afferent pain pathway rather than a central analgesiceffect,similartothemechanismofondansetron.16
Ondansetron exhibits the properties of a local anesthetic and relieves pain on injection of propofol without any adverseeffects.17,18 Theeffectof ondansetron,lidocaine,
tramadol, and fentanyl have all been previously studied indecreasingintensityofrocuroniuminjectionpain.19,20In
anotherstudyeffectofondansetronhasbeencomparedwith lidocaineonpain intensity afterrocuronium andpropofol injection.21
618 A.Saliminiaetal.
is NRS, but it is subjective and is difficult to compare it betweendifferentsubjects.Reportedpainlevelsby individ-ualsusingNRSarebasedoneveryindividual’spainthreshold, which is unknown, making the whole results faulty when comparedbetween individuals. Not only a different defi-nitionofpainexistsindifferentculturesaroundtheworld butalsoindividualvariabilityexistsin perceptionof pain. Eveneveryindividual’spainthresholdmaybealteredbased ontheunderlyingemotionalstateandenvironmental situa-tioninwhichthepainisassessed.A‘‘painvision’’system hasbeen recentlyproposedforquantitativeassessmentof pain caused by the removal of adhesive wound dressing materials, which takes into account every patient’s pain threshold.22
Inthisstudyanalmostnewwayofpainassessment,which hasbeen usedinprevious studies ofthe sameauthors.In everyindividual,eachofhandsareusedasacase,we admin-istered the lidocaine in one hand and the granisetron in anotherhandandonepersonscoredpainineachhandatthe sametime.Webelievedthatinthisway,manyof confronta-tionalfactorsareremovedfromthestudy.Inourprevious work in which we assessed the effectof ondansetron on injectionpainofetomidate,oneoftheindividual’shandwas againusedasacaseandanotherhandwasusedascontrol group.11
Toourknowledgeinnearlyallofpreviousinjectionpain assessment studies the method used to assess pain was differenttoour study andpainon injectionwasassessed betweendifferentindividuals.Webelievethatbythis tech-nique,ourresultsaremorereliable.
Thenegativeaspectoflidocaineorgranisetronwasnot measured,becauseallthepatientswereadministeredboth lidocaine and granisetron and there was not any control group. Although the postoperative nausea and vomiting effectofetomidatewasnotmeasured.Thesecanbe con-sideredaslimitationsofthisstudy.
Inconclusion,theresultofthisstudydemonstratedthat, granisetron reduces pain on injection of etomidate more efficientlythanlidocaine.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
Acknowledgement
TheauthorsdeclarethatTehran UniversityofMedical Sci-enceshasfundedthisstudy.
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