REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
PublicaçãoOficialdaSociedadeBrasileiradeAnestesiologiawww.sba.com.br
SCIENTIFIC
ARTICLE
A
comparative
study
between
propofol
and
etomidate
in
patients
under
general
anesthesia
Supriya
Aggarwal,
Vipin
Kumar
Goyal
∗,
Shashi
Kala
Chaturvedi,
Vijay
Mathur,
Birbal
Baj,
Alok
Kumar
DepartmentofAnesthesiaandCriticalcare,MahatmaGandhiMedicalCollegeandHospital,Jaipur,Rajasthan,India
Received12September2014;accepted28October2014 Availableonline12May2015
KEYWORDS Propofol; Inductionof anesthesia; Myoclonus; Hemodynamic stability; Meanarterial pressure
Abstract
Backgroundandobjectives: Induction ofanesthesia isacritical partofanesthesiapractice. Suddenhypotension,arrhythmias,andcardiovascularcollapsearethreateningcomplications followinginjectionofinductionagentinhemodynamicallyunstablepatients.Itisdesirableto useasafeagentwithfeweradverseeffectsforthispurpose.Presentprospectiverandomized study isdesignedtocomparepropofolandetomidatefor theireffectonhemodynamicsand variousadverseeffectsonpatientsingeneralanesthesia.
Methods:HundredASAIandIIpatientsofagegroup18---60yearsscheduledforelectivesurgical procedureundergeneralanesthesiawererandomlydividedintotwogroupsof50each receiv-ingpropofol(2mg/kg)andetomidate(0.3mg/kg)asaninductionagent.Vitalparametersat induction,laryngoscopyandthereafterrecordedforcomparison.Adverseeffectviz.painon injection,apneaandmyoclonuswerecarefullywatched.
Results:Demographic variableswere comparableinboth thegroups.Patients inetomidate groupshowedlittlechangeinmeanarterialpressure(MAP)andheartrate(HR)comparedto propofol (p>0.05) frombaselinevalue. Painoninjectionwas moreinpropofolgroup while myoclonusactivitywashigherinetomidategroup.
Conclusions: Thisstudyconcludesthatetomidateisabetteragentforinductionthanpropofol inviewofhemodynamicstabilityandlesspainoninjection.
© 2015SociedadeBrasileirade Anestesiologia.Publishedby ElsevierEditoraLtda.Allrights reserved.
PALAVRAS-CHAVE Propofol;
Induc¸ãodaanestesia; Mioclonia;
Estudocomparativoentrepropofoleetomidatoempacientessobanestesiageral
Resumo
Justificativaeobjetivos: Ainduc¸ãodaanestesiaéumapartecríticadapráticadeanestesia. Hipotensão súbita,arritmiasecolapsocardiovascularsãocomplicac¸õesameac¸adorasapósa
∗Correspondingauthor.
E-mail:[email protected](V.K.Goyal).
http://dx.doi.org/10.1016/j.bjane.2014.10.005
Estabilidade hemodinâmica; Pressãoarterial média
injec¸ãodeagentedeinduc¸ãoem pacienteshemodinamicamenteinstáveis.Éaconselhávelo usodeumagentesegurocommenosefeitosadversosparaessepropósito.Opresenteestudo prospectivo, randômico teve como objetivo comparar propofol e etomidatoquanto a seus efeitossobreahemodinâmicaeaosváriosefeitosadversosempacientessobanestesiageral.
Métodos: Cem pacientes ASA I e II, idades entre 18-60 anos, programados para procedi-mento cirúrgico eletivo sobanestesia geral foramdivididos aleatoriamente em dois grupos de 50 cadapara receber propofol (2mg/kg) e etomidato (0,3mg/kg) como um agente de induc¸ão.Osparâmetrosvitais nainduc¸ão,laringoscopiae posteriormenteforamregistrados paracomparac¸ão.Efeitosadversoscomodoràinjec¸ão,apneiaemiocloniaforam cuidadosa-mentemonitorados.
Resultados: Asvariáveisdemográficasforamcomparáveisemambososgrupos.Ospacientesdo grupoetomidatoapresentarampoucaalterac¸ãodapressãoarterialmédia(PAM)edafrequência cardíaca(FC)emcomparac¸ãocomogrupopropofol(p<0,05)apartirdovalorbasal.Houve mais doràinjec¸ão nogrupo propofol,enquanto houvemais atividade mioclônicano grupo etomidato.
Conclusões:Esteestudoconcluiqueetomidatoéumagentemelhorparaainduc¸ãoquepropofol emrelac¸ãoàestabilidadehemodinâmicaemenosdoràinjec¸ão.
©2015SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Todosos direitosreservados.
Introduction
Inductionagents aredrugs that,whengiven intravenously inanappropriatedose,causearapidlossofconsciousness. Inductionagentsareusedtoinduceanesthesiapriortoother drugsbeinggiventomaintainanesthesia,asthesoledrugfor shortprocedures,tomaintainanesthesiaforlonger proce-duresbyintravenousinfusion,toprovideconscioussedation duringproceduresundergoinginlocalanesthesiaand inten-sivecareunit.
Propofol, 2,6-diisopropylphenol is most popular induc-tionagent with its favourble characteristics of rapid and smoothinductionandrecovery,decreaseincidenceof nau-seaandvomiting,etc.1,2Whileonothersidedecreaseblood pressure,dosedependentdepressionofventilation,painon injectionarethemajordrawbacks.3---5
Etomidate, carboxylated imidazole is characterized by hemodynamicstability,minimalrespiratorydepressionand cerebralprotectiveeffects.Itslackofeffectonsympathetic nervoussystem,baroreceptorreflexregulatorysystemand itseffectofincreasedcoronaryperfusionevenonpatients withmoderate cardiac dysfunctionmakes it an induction agentofchoiceincardiacdiseasepatients.6---9However,the adverseeffectssuchaspainoninjection,thrombophlebitis andmyoclonusaresomeundesirableadverseeffects.10,11
Thisstudyisanattempttoevaluatetheeffectsof propo-folandetomidatebycomparingcertainparameterssuchas change in blood pressure and heart rate during induction andintubationasaprimaryoutcomeandpainaninjection, myoclonicmovements,Post-operativenauseaandvomiting as a secondary outcome; so that we can choose a safer inductionagent.
Methods
Thisprospectiverandomizeddoubleblindstudyisconducted on 100 patients of American Society of Anaesthesiologist
(ASA)gradeIandIIbetween18and60yearsofageofeither sex,scheduledforelectivesurgicalprocedureundergeneral anesthesiawithendotrachealintubation.
After approval from institutional ethical committee, written informed consent was obtained from all the patients. The total 100 patients were randomly assigned into2groupsof50patientseach accordingtoacomputer generatedtableofrandomnumbers.
• GroupI(n=50):receivedInj.Propofol1%(2mg/kgofbody weight)
• Group II (n=50): receivedInj. Etomidate (0.3mg/kg of bodyweight)
Patientswithhistoryofallergytostudydrugs,historyof seizuredisorder,presenceofprimaryandsecondarysteroid deficiency/onsteroidmedicationandhypotensivepatients wereexcludedfromstudy.
Allpatientswerepre-medicatedwithtabletsalprazolam 0.25mgandranitidine150mg,thenightbeforethesurgery and instructed for fasting for 8h. On arrival at operation theatre, patientswere attachedwithstandard anesthesia monitoringincludingElectrocardiogram(ECG),Non-invasive blood pressure (NIBP), Pulse oximeter and baseline vital parameterswererecorded. An18G intravenous(I.V.) can-nulawassecuredinlefthandandringerlactate10mL/kg/h wasstarted.
Refusal to consent (14)
On steroid medication (2)
16 patients excluded
100 patients were recruited
Propofol (2mg/kg) n=50
Etomidate (0.3mg/kg) n=50
116 patients assessed for eligibility
Figure1 Studydesign.
was maintained withoxygen and nitrousoxide (70:30) in isoflurane along withintermittent boluses of vecuronium, asrequiredthroughout thesurgery.At theendofsurgery, the residual neuromuscular block was antagonized with neostigmine (0.05mg/kg) and glycopyrrolate (0.01mg/kg) I.V. and extubation was performed when respiration was adequateandpatientwasabletoobeyverbalcommands.
Systolicblood pressure,diastolic bloodpressure, mean arterialpressure, heartrate werecontinuouslymonitored and recorded before induction, at induction and laryn-goscopyfollowedby1,3,5and10minutesafterintubation. Painoninjectionwasmeasuredusing4gradedscale;0---no pain,1---verbalcomplaintofpain,2---withdrawalofarm, 3--- bothverbalcomplaintandwithdrawalofarm.The inci-denceanddegreeofmyoclonicmovementsalsorecordedas follows: 0=no myoclonicmovements, 1=minor myoclonic movements,2=moderatemyoclonicmovements,3=major myoclonicmovements. Episode of apnea, ifoccurred was recorded.
Statisticalanalysis
Data are presented as mean±SD. Patient characteristic data were analysed with one way ANOVA for continuous variablesandchi-squaretestforcategoricalvariables. Sta-tisticalanalysiswasdoneusingSPSS20(IBMSPSSStatistics).
p-Value<0.05wasconsideredsignificant.
Results
A total of 116 patients were assessed for eligibility from December2013toMay2014,outofwhich16patientswere excludedfromstudyonaccountofrefusaltoconsent (four-teen patients) andon steroidmedications(two patients). 100patientswerecompletedthestudyafterrandomization intwogroups(Fig.1).
Both groups were comparable in age, sex, weight and ASAphysical status,withnostatisticallysignificant differ-ences (p>0.05) (Table 1). Pre-operative vitals (HR, SBP, DBP and MAP) were comparable in both groups with no statistically significant differences (p>0.05). Decrease in MAPandincreaseinheart ratewasmorefrombaselinein propofolgroupthanetomidategroupatinduction(p>0.05) (Figs.2and3).Fiftypercentofpatientsreceivedpropofol complainedpainwhile onlyfourpercentpatientin etomi-date group(p>0.05).Also,the severityof painwasmore with propofol (Table 2). Incidence of apnea was similar
Table1 Demographiccharacteristicofpatients(p>0.05).
Variable GroupI GroupII
Sex(female:male) 30:20 27:23 Age(years)mean±SD 29.16±11.38 27.86±10.09 Weight(kg)mean±SD 56.02±11.03 57.4±11.16
ASAgradeI/II 26/24 23/27
Baseline At induction At Laryngoscopy
1 min 3 min 5 min 10 min
Group II Group I
40 60 80 100 120
20
0
Figure2 ShowingMAPatdifferenttimeintervals.A
signifi-cantdecreaseinMAPfrombaselineatinductionwithpropofol incomparetoetomidateisobserved(p>0.05),thereafterMAP becamecomparabletoetomidate(p>0.05).
0 20 40 60 80 100 120
Baseline At induction
At lar yngoscop
y
1 min 3 min 5 min 10 min
Group I Group II
Figure3 ShowingHRatdifferenttimeintervals.Increasein
heart rate from baseline at induction is significantly high in propofolgroup(p>0.05),thenbecame comparableto etomi-date(p>0.05).
in both groups (p>0.05) (Table 3). Myoclonic movements wereonly seen in etomidate group (p>0.05). Severity of myoclonuswasnotedasgrade1(20%),grade 2(14%)and grade3(2%)(Table4).
Table2 Incidenceandgradingofpainoninjection.
Group Painoninjection p-Value
Grade0 Grade1 Grade2
Table3 Incidenceofapneaoninductioninbothgroups.
Group Apneaoninduction p-Value
Yes No
GroupI 38(76%) 12(24%) 0.271 GroupII 33(66%) 17(34%)
Table4 Incidenceofmyoclonicmovementsinbothgroups.
Myoclonicmovements GroupI GroupII p-Value
Grade0 50(100%) 32(64%) 0
Grade1 0(0%) 10(20%)
Grade2 0(0%) 7(14%)
Grade3 0(0%) 1(2%)
Discussion
Induction of anesthesia is associated with hemodynamic
variationofmildtomoderatedegreedependinguponmany
factors. In our study, we observed that propofol caused
significanthypotensionandtachycardiaatinductionin
com-parison to etomidate. Hypotension occurs with propofol
is mainly due to reduction of sympathetic activity
caus-ing vasodilation or its direct effect on vascular smooth
muscles.12,13Suddenhypotensionandtachycardiahas dele-teriouseffectsonmaintainingthecirculationtovitalorgans in patients of coronary artery disease, valvular stenosis, uncontrolledhypertensionandshock.Onanotherside hemo-dynamicstabilityobservedwithetomidatemaybeduetoits uniquelackofeffectonthesympatheticnervoussystemand onbaroreceptorfunctions.14,15Mayeretal.16andWuetal.17 alsoconcludedthatetomidatepreservehemodynamic sta-bilityduringanesthesia.
Etomidatedoesnothave itslimitationtonormotensive patients for its hemodynamic peculiarity. In various stud-ies, etomidate shown less cardiovascular depression and minimize use of vasopressor agents than other induction agent in sepsis and critically ill patients. Although eto-midate can cause adrenal insufficiency in these patients in postoperative period, clinical consequence of that is stillunclearover itsadvantage topreventhypotensionat induction.18---21
Painduringinjectionofanestheticagentisabad expe-rienceforpatientwhile itquiteembarrassingsituationfor ananesthesiologist.Etomidateshownafavourbleoutcome andit wasvery well supported by Saricaogluet al.22 and Wu etal.17 in their studies. Both agents had shown simi-larityin their respiratorydepressant effect. The episodes of apnea were transient and not associated withany fall in oxygen saturation. Boysen et al.23 in their study con-cluded that there was no significant difference between two groups (propofol and etomidate) asregard to apnea followinginduction.Theonlynegativecharacteristicnoted withetomidatewashighincidenceofmyoclonicjerks.Miner et al.24 was also concluded high incidence of myoclonus (20% vs. 1.8%) in etomidate and propofol group respec-tively.
Conclusion
Inconclusion,etomidateisbetterforitshemodynamic sta-bility over propofol along with less incidence of pain on injection.Onlydrawbackwashighincidenceofmyoclonus. We thereforesuggest thatetomidate isa betteroption in patients particularlypronetohemodynamic fluctuationat induction likeuncontrolled hypertension,septic, critically illandpatientswithcoronaryarterydisease.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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