REVISTA
BRASILEIRA
DE
ANESTESIOLOGIA
OfficialPublicationoftheBrazilianSocietyofAnesthesiologywww.sba.com.br
SCIENTIFIC
ARTICLE
Effect
of
intraoperative
esmolol
infusion
on
anesthetic,
analgesic
requirements
and
postoperative
nausea-vomitting
in
a
group
of
laparoscopic
cholecystectomy
patients
Necla
Dereli,
Zehra
Baykal
Tutal
∗,
Munire
Babayigit,
Aysun
Kurtay,
Mehmet
Sahap,
Eyup
Horasanli
KeciorenTrainingandResearchHospital,DepartmentofAnesthesiologyandReanimation,Ankara,Turkey
Received14February2014;accepted6August2014 Availableonline22November2014
KEYWORDS
Esmolol;
Postoperativepain;
Postoperative vomitting
Abstract
Purpose: Postoperativepainandnausea/vomitting(PNV)arecommoninlaparoscopic chole-cystectomy patients.Sympatholytic agents mightdecrease requirements for intravenous or inhalation anestheticsandopioids.Inthisstudy we aimedtoanalyze effectsofesmololon intraoperativeanesthetic-postoperativeanalgesicrequirements,postoperativepainandPNV.
Methods:Sixtypatientshavebeenincluded.Propofol,remifentanilandvecuroniumwereused for induction.Studygroupswereasfollows;I---Esmololinfusionwasaddedtomaintenance anesthetics(propofolandremifentanil),II---Onlypropofolandremifentanilwasusedduring maintenance, III--- Esmolol infusion was addedto maintenance anesthetics(desflurane and remifentanil),IV---Onlydesfluraneandremifentanilwasusedduringmaintenance.Theyhave beenfollowedupfor24hforPNVandanalgesicrequirements.Visualanalogscale(VAS)scores forpainwasalsobeenevaluated.
Results:VASscoresweresignificantlylowestingroupI(p=0.001---0.028).PNVincidencewas significantlylowestingroupI(p=0.026).PNVincidencewasalsoloweringroupIIIcomparedto groupIV(p=0.032).AnalgesicrequirementsweresignificantlyloweringroupIandwaslower ingroupIIIcomparedtogroupIV(p=0.005).Heartratesweresignificantlylowerinesmolol groups (groupIandIII)comparedtotheir controls(p=0.001)howeverbloodpressureswere similarinallgroups(p=0.594).Comparisonofesmololgroupswithcontrolsrevealedthatthere isasignificantdecreaseinanestheticandopioidrequirements(p=0.024---0.03).
Conclusion: Usingesmololduringanestheticmaintenance significantlydecreases anesthetic-analgesicrequirements,postoperativepainandPNV.
© 2014SociedadeBrasileirade Anestesiologia.Publishedby ElsevierEditoraLtda.Allrights reserved.
∗Correspondingauthor.
E-mail:[email protected](Z.B.Tutal).
http://dx.doi.org/10.1016/j.bjane.2014.08.007
PALAVRAS-CHAVE
Esmolol;
Dorno
pós-operatório;
Vômitono
pós-operatório
Efeitodainfusãodeesmololsobreanecessidadedeanestesianointraoperatórioe analgesia,náuseaevômitonopós-operatórioemumgrupodepacientessubmetidos àcolecistectomialaparoscópica
Resumo
Objetivo:Adoreaincidênciadenáuseaevômitonoperíodopós-operatório(NVP)sãocomuns em pacientessubmetidosàcolecistectomialaparoscópica. Osagentessimpatolíticos podem diminuiranecessidadedeopiáceosouanestésicosinalatóriosouintravenosos.Nesteestudo, nossoobjetivofoianalisarosefeitosdeesmololsobreanecessidadedeanestésiconoperíodo intraoperatórioedeanalgésiconopós-operatórioeaincidênciadedoreNVP.
Métodos: Sessentapacientesforamincluídos.Propofol,remifentanilevecurônioforamusados para ainduc¸ão.Osgrupos de estudoforam osseguintes: grupoI, ainfusão deesmolol foi adicionadaaosanestésicos(propofoleremifentanil)paramanutenc¸ão;grupoII,apenaspropofol eremifentanilforamusadosduranteamanutenc¸ão;grupoIII,ainfusãodeesmololfoiadicionada aosanestésicos(desfluranoeremifentanil)para manutenc¸ão;grupoIV,apenas desfluranoe remifentanilforamusadosduranteamanutenc¸ão.Operíododeacompanhamentofoi de24 horasparaavaliaraincidênciadeNVPeanecessidadedeanalgésicos.Osescoresdedortambém foramavaliadospormeiodaEscalaVisualAnalógica(EVA).
Resultados: OsescoresEVAforamsignificativamentemenoresnogrupoI(p=0,001---0,028).A IncidênciadeNVPfoisignificativamentemenornogrupoI(p=0,026).NVPtambémfoimenor nogrupoIIIemrelac¸ãoaogrupoIV(p=0,032).Anecessidadedeanalgésicosfoi significativa-mentemenornogrupoIemenornogrupoIIIemrelac¸ãoaogrupoIV(p=0,005).Afrequência cardíacafoisignificativamentemenornosgruposesmolol(gruposIeIII)comparadosaos con-troles (p=0,001), mas a pressão arterialfoi semelhanteem todos os grupos (p=0,594). A comparac¸ãoentreosgruposesmololecontrolesrevelouquehouveumadiminuic¸ão.
Conclusão:Ousodeesmololduranteamanutenc¸ãodaanestesiareduzsignificativamentea necessidadedeanestésico-analgésico,doreincidênciadeNVP.
©2014SociedadeBrasileiradeAnestesiologia.PublicadoporElsevierEditoraLtda.Todosos direitosreservados.
Introduction
Laparoscopic cholecystectomy became a daily routine
procedure with low cost and high patient satisfaction
by developments in surgical and anesthetic techniques.
Despite of high success rates in postoperative pain and
nausea-vomitting (PNV) are still important problems that
delay patient discharge. Intra and postoperative
hemo-dynamic stability and efficient analgesia might prevent
thesecomplications.Inthesepatientshemodynamicstress
responseslikehypertensionandtachycardiamightdevelop
as a reflex to endotracheal intubation or surgical
inter-ventionitself.Insufflationofcarbondioxideintoperitoneal
cavity might also trigger this response. Plasma
concen-trationsof stresshormones might alsoincrease secondary
to side effects of some anesthetic agents. Hemodynamic
instability is an important triggering factor for PNV.1
Dif-ferent techniques or anesthetic agents could be used to
decreasehemodynamicresponseandrelatedpostoperative
complications.2---4Increasingvolatile anesthetic
concentra-tions and/or opioid usage are some methods that could
bepreferred.2 Howeverintraoperative opioids might also
delaypostoperativerecoveryandincreasePNVrates.
Sym-patholyticagents decrease hemodynamic responseand so
requirement for opioids. These agents are alternatives
for opioids and also might decrease requirements for
intravenous or inhalation anesthetics.2---8 In this study we
aimedtoanalyzeeffectsofesmolol,acardioselective
beta-1 (1) adrenergic receptor antagonist, on intraoperative
anesthetic---postoperative analgesic requirements,
postop-erativepainandPNV.
Methodology
Study wasdesigned asa prospective study after approval
fromlocalethicalcommittee(KA174-09012013).60patients
agedbetween18and60yearswhounderwentlaparoscopic
cholecystectomy have been included. Exclusion criterias
were asfollows;previouslyknown cardiovasculardisease,
severe hemodynamical instability during operation [mean
blood pressure (MBP) <70mmHg], chronic opioid usage,
asthma, being obese or underweighted (body mass index
>30 or <18.5), diabetes mellitus, using  blockers or
cal-ciumchannelblockers.Nopremedicationswereusedbefore
operation. Electrocardiographic (ECG), invasive
intraarte-rial blood pressures, MBP, peripheral oxygen saturations
(SpO2)vs.bispectralindex(BIS)monitorizationsweredone
and recordedasstudy data. Propofol2.5mg/kg,
remifen-tanil 1g/kg and vecuronium 0.1mg/kg were used for
inductioninallpatients.50%O2andfreshairmixturewas
levelswereaimedtobebetween35and45mmHgandfresh gasflowratewas3L/mininallpatients.
Studygroupswereasfollows:
Group I: After induction, 5min esmolol infusion (total
dose 1mg/kg) was used. Peroperative esmolol dose was
planned as 10g/kg/min. Maintenance anesthetics were
75---85g/kg/minpropofoland0.2g/kg/minremifentanil.
Group II: Maintenance anesthetics were
75---85g/kg/minpropofoland0.2g/kg/minremifentanil.
Noesmololinfusionwasused.
GroupIII:Afterinduction, 5minesmololinfusion (total
dose 1mg/kg) was used. Peroperative esmolol dose was
planned as 10g/kg/min. Maintenance anesthetics were
4---8%desfluraneand0.2/kg/minremifentanil.
Group IV: Maintenance anesthetics were 4---8%
desflu-ranand0.2/kg/minremifentanil.Noesmololinfusionwas
used.
Group II wasdesignedascontrol for groupIand group
IV was designed as control for group III. Adjustments in
esmolol and other anesthetic drug dosages were done
according toMBPandheart rates ofall individualpatient
as follows. Propofol and desflurane concentrations were
changed continuously during operation by aiming BIS
val-ues between 40-60. Intravenous atropine and ephedrine
were planned to be used in case of any intraoperative
bradycardia(40pulse/min)orhypotension(MBP<70mmHg).
In case of a decrease in heart rates and MBP near to
abovementionedcriticallevelswefirstdecreased
remifen-tanil infusion rates and then decreased esmolol infusion
rates.Totalrequirementsofpropofol,remifentanil,esmolol
and desfluran were calculated and recorded for each
patient.
All patients were followed up in postoperative critical
care(PACU)unitforatleast30minaftersurgery.
Postopera-tiveECG,MBP,heartrates,peripheralSpO2monitorizations
weredoneandrecordedasstudydata.0.5mg/kgtramadol
wasgiventopatientswith>3pointsinvisual analogscale
(VAS)evaluations.10mgmetoclopramideIVwasappliedto
alpatientsinPACU.AllpatientsweredischargedfromPACU
tostandartcare clinicsaftertheyhadanAldretescore>9
andthey have been followedup for another24h for PNV
andanalgesicrequirements.VASwasalsobeenreevaluated
at12thand24thhoursandscores wererecordedasstudy
data.
Statistical
methodology
Statistical Packagefor Social Sciences (SPSSfor Windows,
Chicago, IL, USA)version of 14.0 wasusedfor data
anal-ysis. Data were submitted to a frequency distribution
analysis by Kolmogorov---Smirnov’s test. Values displaying
normal distributionwere expressedas themean±SD and
values with skew distribution were expressed as median
(interquartilerange). Differencesbetween numeric
varia-bles were tested with one-way ANOVA or Kruskal---Wallis
testswhereappropriate.Tukeytestwasusedfor posthoc
analyses. Categorical data were compared by chi-square
or Fisher’s tests. The value of confidence interval was
acceptedas95%andstatisticalsignificancewasacceptedas:
p<0.05.
Results
60laparoscopiccholecystectomypatients(45female,age;
47.8±12.1 years) were included. Study groups were
sta-tisticallysimilarinmeansofdemographic(ageandgender
distribution)chatracteristics(Table1).Surgeryand anesthe-siadurationswerealsosimilarhowevertherewasatendency
for increased surgery (p: 0.054) and anesthesia durations
(p=0.097) in group I and groupII compered to groups III
andIV(Table1).Thesedurationsweresimilarwhenesmolol groupswerecomparedwithonlytheircontrols(groupIvs.II
andgroupIIIvs.IV).MeanBISvaluesweresimilarbetween
groupsandwerebetween40and60(p=0.270).VASscore
measuredinPACU,12thand24thpostoperativehourswere
significantlylowestingroupI(p=0.001,0.003,0.028 respec-tively).PNVincidenceinpostoperative24hwassignificantly lowestingroupIcomparedtoallother groups(p=0.026).
HoweverPNV incidence was also lower in group III
com-paredtoits’control,groupIV(p=0.032).Similarlyanalgesic
requirementsinpostoperative24hweresignificantlylower
ingroup Icomparedtoall other groups and waslowerin
groupIIIcomparedtoits’control,groupIV(p=0.005).When
compared in means of hemodynamical parameters heart
ratesweresignificantlylowerinesmololgroups(groupIand III)comparedtotheircontrols(p=0.001)howeverMBP val-ueswere similarinall groups (p=0.594).Heartrates and
MBPvaluesinPACUweresimilarbetweengroups(p=0.327,
0.094respectively).Comparisonofesmololgroupswith
con-trols in means of anesthetic requirements revealed that
thereis a significant decrease in desfluran, propofol and
remilfentanilrequirements (p=0.024, 0.03, 0.026
respec-tively).
Discussion
Despite of high success rates in laparoscopic
cholecys-tectomyprocedures,postoperative pain andPNV are still
common problems. Efficient postoperative analgesia and
intraoperative hemodynamic stability are very important
factors that affect complication rates in these patients.9
PNV has an incidence 40---75% and usually delays patient
discharge.9,10Femalegender,smoking,previousPNVhistory,
carsicknesshistory,postoperativeopioidusage,
intraopera-tivehypotensionandorthostotichypotensionaremajorrisk
factorsforPNV.11---13
Some modifications in anesthesia protocols are being
researched by clinicians to decrease incidence of these
complications. In this study we observed that decreasing
opioid and anesthetic doses and additionof esmolol into
anesthesia protocol decreases PNV rates and
postopera-tivepaincomlicationrates withoutcausing anysignificant
hemodynamiccomplication.Usinghighopioiddosesindaily
laparascopic procedures might cause a delay in recovery
duration,increasedPNVandurinaryretention rates. Beta
blockerscouldbeusedeffectivelyasalternativeagentsto
decreaseopioid requirements. Possiblepositiveeffects of
betablockers arehemodynamic stability,decreased
anes-theticandanalgesicrequirements,decreasedPNVratesand
decreasedintubationstress.
Effectsofbetablockersinanginapectoris,hypertension
Table1 Comparisonofstudygroups.
GroupI(n=12) GoupII(n=15) GroupIII(n=21) GroupIV(n=12) p-Value
Gender(F/M) 9/3 12/3 15/6 8/4 0.724
Gender(years) 44.3±13.2 45.3±14.2 51.7±9.3 48.8±11.9 0.318
Surgeryduration(min) 79.1±23.9 82.6±31.3 62.2±24.1 55.5±23.5 0.054 Anesthesiaduration(min) 92.1±25.6 91.1±35.7 77.7±22.9 68.1±24.8 0.097
PostoperativeVAS(inPACU) 0.5(1) 3(2) 2(1) 3(2) 0.001
PostoperativeVAS(12thhours) 0.5(1) 2(2) 2(1.5) 2.5(2) 0.003
PostoperativeVAS(24thhours) 0(0) 1(2) 1(2) 0.5(2.75) 0.028
Analgesiarequirementin postoperative24h
2/12(16.7%) 10/15(66.7%) 5/21(23.8%) 8/12(66.7%) 0.005
PNVinpostoperative24h 1/12(8.3%) 6/15(40%) 7/21(33.3%) 8/12(66.7%) 0.03 Intraoperativeheartrate
(pulse/min)
66.4±9.1 77.4±7.5 69.3±6.4 72.8±6.1 0.001
Intraoperativemeanblood pressure(mmHg)
91±15.7 92.1±11.7 91.6±8.3 86.6±10.8 0.594
HeartrateinPACU(pulse/min) 63.6±11.9 72.9±12.4 67.4±12.1 65.7±15.6 0.327 MeanbloodpressureinPACU
(mmHg)
79.7±15.1 89.1±16.3 80.9±13 76.8±9.5 0.094
MeanBISvalue 51.9±20.2 51.7±12.6 46.7±9.4 43.4±8.5 0.270
Propofolrequirements(mL) 328.4±173.8 530.1±244.1 --- --- 0.024a
Desfluranerequirements(mL) --- --- 31.2±12.3 43.6±18.9 0.03b Remilfentanilrequirements(mL) 174.6±100.8 269.2±105.2 132.9±146.0 562.4±152.4 0.026a
0.0001b
ap-Valuebetweengroup1and2. b p-Valuebetweengroup3and4.
todecreaseintraoperativemyocardialischemiainhighrisk
patientsis acommonpracticefor anesthesiologists.
How-everlonghalflifeofpropranalollimitsits’usage.Esmolol
is an ideal beta blocker that has shorter half life and
cardioselectivity.Its’ effectstart fast and alsogets elim-inated in a shorttime witha half life of 9.2±2min.16 It
shows its’ maximal effect on heart rate and blood
pres-surein1---2minafterintravenousinjection.17Esmololcould
be used by intravenous infusion or boluses due to its’
pharmacodynamicandpharmacokineticproperties.Esmolol
supresses adrenergic response against laryngoscopy,
tra-chealintubation---extubationandperitonealirritationdueto CO2insufflationduringlaparoscopy.Usingesmololinfusion
intraoperatively gives opportunity to control sympathetic
system response and there by decrease myocardial O2
consumption.18---21 Itwasalsoreportedtodecrease
periop-erativenausearesponse.22
In patients who received esmolol with standart
anes-thesia protocol (groups I and III) we observed that
intraoperative heart rates were significantly lower,
how-ever therewas nosignificant differencein intraoperative
MBP compared to control groups. We also observed that
therewasno significant difference between study groups
and controls in means of heart rates and blood pressure
duringrecoveryphaseinPACU.Dependingonthesefindings
wethinkthatbyclosehemodynamicfollow-upandtitrating
esmololdoses,anesthesiologistcouldavoidunwantedside
effectsofesmolollikehypotension,andalsocouldusethis
dosetitrationadvantageanddecreasedintraoperativeheart
ratestodecreasemyocardial O2requirements. Supporting
our findings Smith and colleques compared esmolol and
alfentanilinmeansofhemodynamicstabilityinagroupof
arthroscopicsurgerypatientsandreportedthatesmololas
agoodalternativewithlesssideeffects.1Colomaand
colle-quesalsocomparedesmololwithremilfentanilinmeansof
hemodynamic stability in agroup of laparascopic
gyneco-logical surgery patients and reported it provides a beter
hemodynamicstability.5
Remifentanil is a synthetic opioid agonist. Its’ effects
reachesmaximallevelsinarelativelyshortperiodoftime.
Itiseliminatedbytissueandbloodesterasesandhasavery
shorthalf life.23 Becauseof these propertiesremifentanil
isagoodalternativeforfentanyl.24However,insome
stud-iesremifentanilwasreportedtocausehypotension.Hogue
andcollequesreportedthat 20%of patientswhoreceived
remifentanildevelopedhypotension.25 Schuttlerand
colle-ques and McAtamney and colleques also reported similar
resultsintwodifferentstudies.26,27Inourstudyweobserved
that addition of esmolol decreases remifentanil
require-mentssignificantly.Dependingonthesefindingswebelieve
that addingesmolol inanesthesiaprotocols with
remifen-tanilwillsignificantlydecreasehemodynamiccomplications
and hypotension. According to our findings addition of
esmololalsodecreasesrequirementsforpropofoland
desflu-rane.Itcouldeasilybeforeseenthatdecreasedanesthetic
requirementswillcauselesssideeffectsandalsoadecrease
in economical cost.Supporting ourfindings Johansen and
collequesreportedsimilarresults.Theycomparedeffectof
esmololadditiononpropofoland60%N2Orequirementsand
observedthatesmololsignificantlydecreasesrequirements
forbothagents.7IntwodifferentstudiesTopc¸uetal.28and
Wilson et al.29 reported esmolol decreased both propofol
andremifentanilrequirements.Chiaandcollequesreported
and also postoperative analgesia and morphine usage.30
Moon and colleques reported that using esmolol might
decrease PACUrecovery duration in gynecological surgery
patients.6
In this study we observed that besides lowering
anesthetic requirements adjuvant esmolol also decreases
analgesicrequirementsandVASscoresinpostoperative24h.
Somepreviousstudiesalsosupportedourfindings.Bhawna
and colleques reported that in lower abdominal surgery
patients addition of esmolol to isofluranemight decrease
bothanesteticandpostoperativeanalgesicrequirements.31
ÖztürkandcollequesreportedthatbothPNVincidenceand
analgesic requirementsdecreasein laparoscopic
cholecys-tectomypatientsbyadjuvantesmolol. Twosimilarstudies
alsoreportedadecreaseinpostoperativepainandanalgesic
requirements.8 Previous studies demonstrated emotional
stress,fearandanxiety triggershippocampalactivationin
magnetic resonance imaging. These changes were hought
to be secondary to a neuroactive substance like
norepi-nephrine. Hippocampal N-methyl-d-aspartate (NMDA) and
adrenergic receptors are thought to play role in
percep-tion.Blockageofthesereceptorsmaydecreaseactivationof
adrenergicactivityandsopain.32 Betablockersmightalso
decreasehepaticbloodflow andmetabolismofboth their
andotherdrugsandasaresultmightdecreasepostoperative
analgesicrequirements.33,34
Anotherfindingweobservedinourstudywasdecreased
PNVandantiemeticrequirementsinpatientswhoreceived
esmolol. Hypertensive patients or the ones who develop
postoperativehypotensionwerereportedtohaveincreased
PNVincidencecomparedtootherpopulations.35Forthis
pur-pose hemodynamic stability during and just after surgery
is important to prevent PNV.36 From this perspective we
foundthatpatientswhoreceivedesmololdidnothaveany
bloodpressureabnormality(hypoorhypertension)andalso
requiredlowerdosesofopioidagents,whicharewellknown
nauseaandvomittingtriggeringagents.Wethinkthatthese
mightbethecauseofdecreasedPNVratesinthesepatients.
Howeverthereisconflictingfindingsinliteraturethat
evalu-atedtherelationshipbetweenesmololandPNV.Öztürkand
collequesandColomaandcollequesreportedsimilar
find-ingswithourstudy.5,8OntheotherhandSmithandcolleques
didnotobserveanysuperiorityofesmololinmeansofPNV.1
Mainpurposeofthisstudywasobservingandcomparing
effectsofaddingesmololtostandartanestheticprotocols.
On the other hand we also had opportunity to compare
propofol-remifentanil based and desflurane-remifentanil
based anesthesiaprotocols. According toour findings VAS
scoremeasuredinPACU,12thand24thpostoperativehours
weresignificantly lowest ingroup I(propofol-remifentanil
afteresmolol).PNVincidenceinpostoperative24hwasalso
significantlylowestingroupIcomparedtoallothergroups.
Similarlyanalgesicrequirementsinpostoperative24hwere
significantlylowerinthesepatientscomparedtoallother
groups.Dependingonthesefindingswethinkthatpropofol
based anesthesia protocols might be advantageous
com-paredtodesfluranebasedprotocols.Supportingourfindings
Song etal. reported that propofol was significantly more
effective compared to desflurane in means of preventing
PNV.37Howeverinmeansofpainpreventiontherearesome
datainliteraturethatcontradictsourfindings.Hepa˘gus¸lar etal.,Fassoulakietal.,Ortizetal.reportedthatthereis
nosignificantdifferencebetweenpropofolandsevoflurane
ordesfluranebasedanesthetic protocolsinmeans of post
operative pain prevention in 3 different studies.38---40 This
fieldneedsmorestudiesforclarification.
As a conclusion we observed that using adjuvant
esmolol during anesthetic maintenance of laparoscopic
cholecystectomy patients decreases anesthetic---analgesic
requirements, postoperative pain and PNV without
caus-ing any hemodynamic instability. We also observed that
propofol-remifentanilbasedanesthesiaprotocolsmightbe
advantageous in means of PNV and pain prevention
com-paredtodesflurane-remifentanilbasedprotocols.
Conflicts
of
interest
Theauthorsdeclarenoconflictsofinterest.
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