Dexmedetomidine Infusion During Laparoscopic Bariatric Surgery The Effect on Recovery Outcome

AnestheticPharmacologyPreclinicalPharmacology

SectionEditor:MarcelE.DurieuxClinicalPharmacology

SectionEditor:TonyGin

DexmedetomidineInfusionDuringLaparoscopicBariatric

Surgery:TheEffectonRecoveryOutcomeVariables

BurcuTufanogullari,MD*

PaulF.White,PhD,MD*

MarianaP.Peixoto,MD*

DanielKianpour,MS*

ThomasLacour,MD*

JamesGriffin,MD*

GarySkrivanek,MD*

AmyMacaluso,MD*

MaryShah,MD*

DavidA.Provost,MD†BACKGROUND:Dexmedetomidine(Dex),an␣2agonist,haswell-knownanestheticandanalgesic-sparingeffects.Wedesignedthisprospective,randomized,double-blind,andplacebo-controlleddose-rangingstudytoevaluatetheeffectofDexonbothearlyandlaterecoveryafterlaparoscopicbariatricsurgery.METHODS:EightyconsentingASAII–IIImorbidlyobesepatientswererandomlyassignedto1of4treatmentgroups:(1)controlgroupreceivedasalineinfusionduringsurgery,(2)Dex0.2groupreceivedaninfusionof0.2␮g⅐kgϪ1⅐hϪ1IV,(3)Dex0.4groupreceivedaninfusionof0.4␮g⅐kgϪ1⅐hϪ1IV,and(4)Dex0.8groupreceivedaninfusionof0.8␮g⅐kgϪ1⅐hϪ1IV.MeanarterialbloodpressurevaluesweremaintainedwithinϮ25%ofthepreinductionbaselinevaluesbyvaryingtheinspireddesfluraneconcentration.Perioperativehemodynamicvariables,postop-erativepainscores,andtheneedfor“rescue”analgesicsandantiemeticswererecordedatspecificintervals.Follow-upevaluationswereperformedonpostop-erativedays(PODs)1,2,and7toassessseverityofpain,analgesicrequirements,patientsatisfactionwithpainmanagement,qualityofrecovery,aswellasresump-tionofdietaryintakeandrecoveryofbowelfunction.RESULTS:Dexinfusion,0.2,0.4,and0.8␮g⅐kgϪ1⅐hϪ1,reducedtheaverageend-tidaldesfluraneconcentrationby19,20,and22%,respectively.However,itfailedtofacilitateasignificantlyfasteremergencefromanesthesia.Althoughtheintra-operativehemodynamicvaluesweresimilarinthefourgroups,arterialbloodpressurevaluesweresignificantlyreducedintheDex0.2,0.4,and0.8groupscomparedwiththecontrolgrouponadmissiontothepostanesthesiacareunit(PACU)(PϽ0.05).ThelengthofthePACUstaywassignificantlyreducedintheDexgroups(81Ϯ31to87Ϯ24vs104Ϯ33mininthecontrolgroup,PϽ0.05).TheamountofrescuefentanyladministeredinthePACUwassignificantlylessintheDex0.2,0.4,and0.8groupsversuscontrolgroup(113Ϯ85,108Ϯ67,and120Ϯ78vs187Ϯ99␮g,respectively,PϽ0.05).ThepercentageofpatientsrequiringantiemetictherapywasalsoreducedintheDexgroups(30,30,and10%vs70%inthecontrolgroup).However,thepatient-controlledanalgesiamorphinerequire-mentsonPODs1and2werenotdifferentamongthefourgroups.PainscoresinthePACU,andonPODs1,2,and7,inthethreeDexgroupswerenotdifferentfromthecontrolgroup.Finally,qualityofrecoveryscoresandtimestorecoveryofbowelfunctionandhospitaldischargedidnotdifferamongthefourgroups.CONCLUSIONS:AdjunctiveuseofanintraoperativeDexinfusion(0.2–0.8␮g⅐kgϪ1⅐hϪ1)decreasedfentanyluse,antiemetictherapy,andthelengthofstayinthePACU.However,itfailedtofacilitatelaterecovery(e.g.,bowelfunction)orimprovethepatients’overallqualityofrecovery.Whenusedduringbariatricsurgery,aDexinfusionrateof0.2␮g⅐kgϪ1⅐hϪ1isrecommendedtominimizetheriskofadversecardiovascularsideeffects.

(AnesthAnalg2008;106:1741–8)

D

exmedetomidine(Dex)isahighlyselective␣2-

adrenoreceptoragonist,whichpossesseshypnotic,sedative,anxiolytic,sympatholytic,andanalgesic

propertieswithoutproducingsignificantrespiratory

depression.1–4Itssympatholyticeffectdecreasesmean

arterialbloodpressure(MAP)andheartrate(HR)by

reducingnorepinephrinerelease.5,6Inaddition,Dex

hastheabilitytoreduceboththeanestheticandopioid

analgesicrequirementsduringtheperioperativeperiod.7–9

Asaresultoftheprevalenceofobesityinmodern

societies,bariatricsurgerycontinuestogrowthroughoutFromtheDepartmentsof*Surgery,†AnesthesiologyandPainManagement,UniversityofTexasSouthwesternMedicalCenteratDallas,Dallas,Texas.

AcceptedforpublicationFebruary8,2008.

Thisinvestigator–initiated,FoodandDrugAdministration-approvedstudywassupported,inpart,byanunrestrictededuca-tionalgrantfromHospira,Inc.(LakeForest,IL),endowmentfundsfromtheMargaretMilamMcDermottDistinguishedChairinAn-esthesiology,andtheWhiteMountainInstitute,anon-profitprivatefoundation(PaulF.White,President).

AddresscorrespondenceandreprintrequeststoDr.PaulF.White,ProfessorandHolderoftheMargaretMilamMcDermottDistinguishedChairinDepartmentofAnesthesiologyandPainManagement,UniversityofTexasSouthwesternMedicalCenteratDallas,5323HarryHinesBoulevard,Dallas,TX75390-9068.Ad-dresse-mailtopaul.white@utsouthwestern.edu.

Copyright©2008InternationalAnesthesiaResearchSocietyDOI:10.1213/ane.0b013e318172c47c

Vol.106,No.6,June20081741theworld.Morbidlyobesepatientsareatanincreased

riskofdevelopingpostoperativeobstructivesleepapnea

andopioid-inducedventilatorydepression.SinceDex

possessesanopioid-sparingeffectwithoutcausingrespi-

ratorydepression,ithasbeenincreasinglyused“off-

label”duringbariatricsurgery.10,11However,thereis

onlyonestudydescribingtheuseofanarbitrarily

chosenDexinfusionrateinthispatientpopulation.12

Inthisprospectivelyrandomized,double-blind,

placebo-controlled,dose-rangingstudy,wetestedthe

hypothesisthatDexinfusionwouldproducedose-

relatedreductionsintheanestheticandanalgesic

requirementsinpatientsundergoinglaparoscopic

bariatricsurgery.Thesecondaryobjectiveswereto

determineiftheuseofDexfacilitatedtherecovery

processandimprovedpatientoutcome.

METHODS

AfterobtainingIRBapprovalattheUniversityof

TexasSouthwesternMedicalCenteratDallas,and

writteninformedconsent,80morbidlyobesepatients,

aged22–66-yr-of-age,scheduledforlaparoscopicbari-

atricsurgery(eithergastricbandingorgastricbypass)

werestudiedaccordingtoarandomized,double-

blind,placebo-controlledprotocol.Thisinvestigation

wasregisteredwithClinicalTrials.gov(NCT00363935).

Patientswereexcludediftheyhad:(1)anallergyto␣2adrenergicagonistorsulfadrugs,(2)ahistoryof

uncontrolledhypertension,(3)heartblockgreater

thanfirstdegree,(4)ahistoryofalcoholordrugabuse,

(5)clinicallysignificantneurologic,cardiovascular,

renal,hepatic,orgastrointestinaldiseases,(6)received

anopioidanalgesicmedicationwithina24hperiod

beforetheoperation,(7)werepregnantorbreast-

feeding,and(8)wereunabletospeakandread

English.

Thepatientswererandomlyassignedusinga

computer-generatedrandomnumbertabletooneofthe

followingfourtreatmentgroups:(1)controlgroupreceived

saline,(2)Dex0.2groupreceived0.2␮g⅐kgϪ1⅐hϪ1IV,(3)

Dex0.4groupreceived0.4␮g⅐kgϪ1⅐hϪ1IV,and(4)

Dex0.8groupreceived0.8␮g⅐kgϪ1⅐hϪ1IV.The

studymedicationwaspreparedbytheoperatingroom

(OR)pharmacistinidentical60-mLsyringes.Dex0,

200,400,or800␮gwasaddedtosalinetoachievea

totalvolumeof40mL,resultinginconcentrationsof0␮g/mL(control),5␮g/mL,(Dex0.2),10␮g/mL,(Dex

0.4),and20␮g/mL,(Dex0.8),forthe4studygroups.

Theweight-adjusteddosesofallstudymedications

werebasedonthepatient’sactualbodyweight.The

investigators,attendinganesthesiologists,OR,recov-

eryandwardnurses,aswellasthepatientswere

blindedtothecomputer-generatedrandomization

schedule.

Inthepreoperativeholdingarea,thepatientsused

11-pointverbalratingscales(VRS)toassesstheir

baselinepainandnausealevels,with0ϭnoneto10ϭ

maximum.Celecoxib,400mgorally,wasgiven30–60minbeforeinductionofanesthesia.Immediatelybe-

foreenteringtheOR,patientswerepremedicatedwith

midazolam,20␮g/kgIV.Intraoperativemonitoring

devicesincludednoninvasivearterialbloodpressure,

electrocardiography,capnography,andpulseoxim-

etry,aswellasthecerebralstatemonitor(Danmeter,

Odense,Denmark).

AfterobtainingbaselinemeasurementofHRand

MAP,aninfusionofthestudymedicationwasstarted

at0.04mL⅐kgϪ1⅐hϪ1.Anesthesiawasinduced3–5

minafterstartingthestudydruginfusionwithpropo-

fol,1.25mg/kgIV,incombinationwithlidocaine,0.75

mg/kgIV.Rocuronium,0.6mg/kgIV,and4mLof

topical4%lidocainewereadministeredbeforetra-

chealintubation.Anesthesiawasinitiallymaintained

with4%inspiredconcentrationofdesfluraneincom-

binationwithair(1L/min)andoxygen(1L/min)

mixture.

TheintraoperativeHR,MAP,end-tidaldesflurane

concentration,andcerebralstateindex(CSI)values

wererecordedat5minintervalsfor30min,and

subsequentlyat10minintervalsuntildiscontinuation

oftheanestheticdrugs.Hemodynamicvalueswere

alsorecordedatspecificend-points(e.g.,inductionof

anesthesia,1minafterinduction,trachealintubation,

5minaftertrachealintubation,atskinincision,at5

and10minaftertheskinincision).Afterinductionof

anesthesia,MAPvaluesweremaintainedwithinϮ25%ofthebaselinevaluesbyvaryingtheinspired

desfluraneconcentration.Hypotension(definedas

MAPvalueϽ25%ofthebaselinevalueontwocon-

secutivereadingswithin2–3min),notrespondingtoa

2%(vol%)decreaseintheinspireddesfluranecon-

centrationanda200mLfluidbolus,wastreatedwith

phenylephrine,100␮gIV,boluses.Theinfusionof

studymedicationwasdiscontinuedifthehypotension

persistedϾ2minaftertheseinterventions.Upon

returnoftheMAPtoϮ25%ofthebaselinevalue,the

studymedicationinfusionwasresumedat50%ofthe

initialinfusionrate.Inthepresenceofhypertension

(definedasMAPvalueϾ25%ofthebaselinevalueon

twoconsecutivereadingswithin2–3min)and/or

tachycardia(definedasHRvalueϾ25%ofthebase-

linevalueϾ2min)despitea2%(vol%)increaseinthe

inspireddesfluraneconcentration,labetalol,5mgIV,

boluseswereadministered.Bradycardia(HRϽ45)

persistingforϾ2minwastreatedwithglycopyrrolate,

0.2mgIV,boluses.

Duringtheoperation,patientsreceivedsimilar

amountsofIVcrystalloidsolutions(namely,25

mL/kgduringgastricbypassand10mL/kgduring

gastricbandingprocedures).Ondansetron,4mgIV,

wasgivenforpreventionofpostoperativenauseaand

vomitingwhenthelaparoscopewaswithdrawn.Be-

forewoundclosure,bupivacaine0.25%wasinfiltrated

atthefasciallevelofallportals,andresidualneuro-

muscularblockwasreversedwithneostigmine,40␮g/kgIV,andglycopyrrolate,5␮g/kgIV.Theinfu-

sionofstudymedicationwasdiscontinuedatthestart

1742DexmedetomidineInfusionandBariatricSurgeryANESTHESIA&ANALGESIA