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2017525 TreatmentofacutecalculouscholecystitisUpToDate

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www.uptodate.com2017UpToDate

Treatmentofacutecalculouscholecystitis

Authors: CharlesMVollmer,Jr,MD,SalamFZakko,MD,FACP,NezamHAfdhal,MD,FRCPI
SectionEditor: StanleyWAshley,MD
DeputyEditor: WenliangChen,MD,PhD

Alltopicsareupdatedasnewevidencebecomesavailableandourpeerreviewprocessiscomplete.
Literaturereviewcurrentthrough:Apr2017.|Thistopiclastupdated:Mar15,2017.

INTRODUCTIONAcutecholecystitisreferstoasyndromeofrightupperquadrantpain,fever,andleukocytosis
associatedwithgallbladderinflammation,whichisusuallyrelatedtogallstonedisease(ie,acutecalculous
cholecystitis).Complicationsincludethedevelopmentofgangreneandgallbladderperforation,whichcanbelife
threatening.

Thetreatmentofacutecalculouscholecystitiswillbereviewedhere.Theapproachtopatientswithasymptomatic
gallstones,theapproachtothepregnantpatientwithgallstones,andtheclinicalmanifestationsanddiagnosisof
biliarycolic,acutecholecystitisandrelatedconditions,suchasacalculousandxanthogranulomatouscholecystitis,
arediscussedseparately.(See"Uncomplicatedgallstonediseaseinadults"and"Approachtothepatientwith
incidentalgallstones"and"Choledocholithiasis:Clinicalmanifestations,diagnosis,andmanagement"and
"Gallstonesinpregnancy"and"Acutecholecystitis:Pathogenesis,clinicalfeatures,anddiagnosis"and
"Acalculouscholecystitis"and"Xanthogranulomatouscholecystitis".)

OVERVIEWOFTREATMENTOnceapatientdevelopssymptomsorcomplicationsrelatedtogallstones
(biliarycolic,acutecholecystitis,cholangitis,and/orpancreatitis),definitivetherapy(cholecystectomy,
cholecystostomy,endoscopicsphincterotomy,medicalgallstonedissolution)isrecommended.Withouttreatment
toeliminatethegallstones,thelikelihoodofsubsequentsymptomsorcomplicationsishigh.Complicationsinclude
thedevelopmentofgangreneandgallbladderperforation,whichcanbelifethreatening.(See'Morbidityand
mortality'below.)

IntheNationalCooperativeGallstoneStudy,atrialofnonsurgicaltreatmentwithchenodiolforbiliarytract
pain,demonstratedthattheriskofrecurrentsymptomsforuntreatedpatientswasapproximately70percent
duringthetwoyearsfollowinginitialpresentation[1].

Inacohortstudyof25,397patientsfromOntario,Canadawithafirstepisodeofuncomplicatedacute
cholecystitis,10,304didnotundergocholecystectomyontheirfirstadmission[2].Duringamedian3.4years
offollowup,24percentofpatientshadagallstonerelatedeventwiththemajorityofeventsoccurringwithin
thefirstyear(88percent).Theriskwashighestamong18to34yearoldpatients.Amongtheevents,30
percentwereforbiliaryobstructionorpancreatitis.

AreviewoftheUnitedStatesMedicaredatabasethatincluded29,818elderlypatientswithacute
cholecystitis,foundahigherriskformortalityoverthefollowingtwoyearsinpatientswhoweredischarged
withoutsurgerycomparedwithpatientswhounderwentcholecystectomyintheinitialhospitalization(hazard
ratio[HR]1.56,95%CI1.471.65)[3].

Ourtreatmentapproachisasfollows(algorithm1):

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Patientswithacutecholecystitisshouldbeadmittedtothehospitalforsupportivecare,whichincludes
intravenousfluidtherapy,correctionofelectrolytedisorders,andcontrolofpain.Antibioticsmayalsobe
indicated.(See'Supportivecare'below.)

Theselectionandtimingofdefinitivetherapydependsupontheseverityofsymptomsandthepatient's
overallriskforcholecystectomy.(See'Medicalriskassessment'below.)

Ifgangreneorperforationaresuspected,orifthepatientdevelopsprogressivesymptomsandsignssuchas
risingfever,hemodynamicinstability,orintractablepainwhileonsupportivetherapy,emergency
cholecystectomyorgallbladderdrainagemaybeneeded(image1).(See'Timingofcholecystectomy'below
and'Subsequentcarefollowingdrainage'below.)

Lowriskpatientswithoutemergentindicationsforinterventiongenerallyundergolaparoscopic
cholecystectomypreferablyduringthesameadmission.(See'Lowriskpatients'below.)

Highriskpatientswithoutemergentindicationsforinterventionaretreatedwithagallbladderdrainage
procedureifsymptomsdonotimprovewithsupportivecare.Forpatientswhosemedicalstatuscanbe
optimizedtoallowsurgery,cholecystectomycanbeconsidered.(See'Highriskpatients'below.)

SUPPORTIVECAREPatientsdiagnosedwithacutecalculouscholecystitisshouldbeadmittedtothehospital.
Patientshaveoftenbeenillfordayspriortoseekingmedicalattention,makingintravenoushydrationand
correctionofanyassociatedelectrolytedisordersanimportantinitialmeasureinthefirst24to48hoursafter
admission.

Patientsshouldbekeptfasting,andalthoughuncommonlyneeded,thosewhoarevomitingshouldhave
placementofanasogastrictube.(See"Nasogastricandnasoenterictubes".)

PaincontrolPaincontrolinpatientswithacutecholecystitiscanusuallybeachievedwithnonsteroidalanti
inflammatorydrugs(NSAIDs)oropioids.Progressionofpainduringtreatmentforacutecholecystitis,despite
adequateanalgesia,isanindicatorofaclinicalprogression.

Wepreferketorolac(30to60mgadjustedforageandrenalfunctiongiveninasingleintramusculardose)for
patientswithbiliarycolic.Treatmentusuallyrelievessymptomswithin20to30minutes.Opioids,suchas
morphine,hydromorphone,ormeperidineareappropriatetherapyforpatientswhohavecontraindicationsto
NSAIDsorwhodonotachieveadequatepainreliefwithanNSAID,whichmaybemorecommoninpatientswith
acutecholecystitiscomparedwithuncomplicatedgallstonedisease.

Itwastraditionallythoughtthatmeperidinewastheopioidofchoiceinpatientswithgallstonediseasebecauseit
haslessofaneffectonsphincterofOddimotilitythanmorphine[46].However,asystematicreviewfoundthatall
opioidsincreasesphincterofOddipressure[5].Thereareinsufficientdatatosuggestthatmorphineshouldbe
avoided.Morphinehasanadvantagethatitrequireslessfrequentdosingthanmeperidine,whichhasashorter
halflife.

AntibioticsAcutecholecystitisisprimarilyaninflammatoryprocess,butsecondaryinfectionofthegallbladder
canoccurasaresultofcysticductobstructionandbilestasis[7,8].Therateofempyemaandpericholecystic
abscessisoveralllow,butpatientscaneasilydeveloplifethreateninggramnegativesepsisfromuncomplicated,
acutecholecystitis.Thus,antibioticsarecommonlyadministeredattheoutsettoprotectagainstsepsisand
woundinfection[9].Studiesareconflictingastowhetherantibioticsarerequiredforthetreatmentof
uncomplicated,acutecholecystitis[7,8,1012].Onestudyof302patientsshowedalowerrateofbacteremiaand
woundinfection,butnodifferenceinthedevelopmentofempyemaofthegallbladderorpericholecystic
abscesseswiththeadministrationofantibiotics[13].Thisislikelyduetotheobstructiontobileflowthatinterferes
withachievingadequategallbladderbileconcentrationsofantibiotics.
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Manycliniciansroutinelyadministerantimicrobialtherapytoallpatientsdiagnosedwithacutecholecystitis,which
arecontinueduntilthegallbladderisremovedorthecholecystitisclinicallyresolves.Othersadvocatethat
antimicrobialtherapyshouldonlybeinstitutedifinfectionissuspectedonthebasisoflaboratory(morethan
12,500whitecellspercubicmillimeter)orclinicalfindings(temperatureofmorethan38.5C),orinpatientswitha
diagnosisofacutecholecystitisandradiographicfindingsindicativeofgallbladderrupture,ischemiaornecrosis
(eg,airinthegallbladderorgallbladderwall).Routineantibioticsarealsorecommendedinolderpatientsorthose
withdiabetesorimmunodeficiencywithadiagnosisofacutecholecystitisregardlessofthesesigns[10,14].(See
"Sepsissyndromesinadults:Epidemiology,definitions,clinicalpresentation,diagnosis,andprognosis".)

Whenempiricantibiotictherapyisindicated,thechosenagent(s)shouldcoverthemostcommonpathogensof
theEnterobacteriaceaefamily,includingGramnegativerodsandanaerobesactivityagainstenterococciisnot
required[8].Inastudyof467patients,includingacontrolgroupof42withnormalbiliarytrees,positivebile
cultureswerefoundin22percentofpatientswithsymptomaticgallstonesand46percentofpatientswithacute
cholecystitis[15].ThemostfrequentisolatesfromthegallbladderorcommonbileductwereEscherichiacoli(41
percent),Enterococcus(12percent),Klebsiella(11percent),andEnterobacter(9percent).Wheneverpossible,
thechosenagent(s)shouldalsoachieveadequateconcentrationsinbile.

TheguidelinesoftheInfectiousDiseasesSocietyofAmericarecommendthefollowingantibioticregimensfor
patientswithacutecholecystitis[10](table1):

Forpatientswithcommunityacquiredacutecholecystitisofmildtomoderateseverity:cefazolin,cefuroxime,
orceftriaxone.

Forpatientswithcommunityacquiredacutecholecystitisofseverephysiologicdisturbance,advancedage,
orimmunocompromisedstate:imipenemcilastatin,meropenem,doripenem,piperacillintazobactam,
ciprofloxacinplusmetronidazole,levofloxacinplusmetronidazole,orcefepimeplusmetronidazole.

Forpatientswithhealthcareassociatedbiliaryinfectionofanyseverity:imipenemcilastatin,meropenem,
doripenem,piperacillintazobactam,ciprofloxacinplusmetronidazole,levofloxacinplusmetronidazole,or
cefepimeplusmetronidazole,withvancomycinaddedtoeachregimen.

Thechoosingofanantibioticregimenwithineachpatientcategoryisgovernedbylocalpractices,takinginto
considerationtheantibiogramandformularyofeachinstitution.Thechosenagentsshouldsubsequentlybe
tailoredtocultureandsusceptibilityresultswhentheybecomeavailable[7].

Thedurationofantibiotictherapyisgenerallytailoredtotheclinicalsituation.Amulticentertrialrandomly
assigned414patientshospitalizedformildormoderatecalculouscholecystitistocontinuetheirpreoperative
antibioticregimenforfivedays(2gamoxicillinplusclavulanicacid,threetimesdaily)ortoreceivenoantibiotics
followingcholecystectomy[16].Nosignificantdifferencesinpostoperativeinfectionrates(17versus15percent)
werefound.Theseresultssupportourcurrentpracticeofdiscontinuingantibioticsthedayafterthe
cholecystectomyforpatientswithuncomplicatedcholecystitis.Clinicaljudgementshoulddictateantibiotic
managementinmorecomplicatedscenarios,suchasinthesepticpostoperativepatient.

Theneedforprophylacticantibioticsatthetimeofsurgeryintheabsenceofclinicalsymptoms/signsofbiliary
infectionisdiscussedelsewhere.(See"Opencholecystectomy",sectionon'Prophylacticantibiotics'and
"Laparoscopiccholecystectomy",sectionon'Antibiotics'.)

Antibiotictherapyforintraabdominalinfections,includingacutecholecystitis,isalsodiscussedindetail
elsewhere.(See"Antimicrobialapproachtointraabdominalinfectionsinadults".)

MEDICALRISKASSESSMENTTheAmericanSocietyofAnesthesiologists(ASA)physicalstatus
classificationiscommonlyusedtostratifytheriskofsurgery(table2)[17].Othermethodstospecificallyassess
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cardiacorpulmonaryriskarediscussedelsewhere.(See"Overviewofanesthesiaandanestheticchoices"and
"Evaluationofcardiacriskpriortononcardiacsurgery"and"Evaluationofpreoperativepulmonaryrisk".)

LOWRISKPATIENTS

TimingofcholecystectomyEarlycholecystectomy,ratherthandelayedcholecystectomy(>7daysafter
admission),ispreferableforpatientswhorequirehospitalizationforacutecholecystitisandwhoaregood
candidatesforcholecystectomy.Evidencefromlargedatabasereviewsandrandomizedtrialsshowthat
cholecystectomyperformedearlyduringtheinitialhospitalizationmaybeassociatedwithreducedperioperative
morbidityandmortalityinsomepatients,andreducesthelengthofhospitalstayandcost[3,1830].

Thebestdatacomefromametaanalysisof15trialsincluding1625patients[31].Comparedwithdelayed
laparoscopiccholecystectomy,earlylaparoscopiccholecystectomy(performedwithinsevendaysofsymptom
onset)wasassociatedwithlesswoundinfection(relativerisk0.65,95%CI0.470.91),ashorterhospitalstay
(meandifference[MD]3days,95%CI4to2),fewerworkdayslost(MD11days,95%CI16to6),buta
longeroperativetime(MD11minutes,95%CI518).Earlysurgerydidnotincreasetherateofmortality,bileduct
injury,bileleakage,conversiontoopensurgery,oroverallcomplications.

Alargeadministrativedatabasestudyofover15,000cholecystectomiesforacutecholecystitisprovidedeven
moregranulardataonhowtimingofcholecystectomycanimpactpatientoutcomes[32].Inthatstudy,therateof
intraoperativelydetectedbiliaryinjurywasthelowestinpatientswhounderwentsurgeryonthedayofadmission
therateincreaseddaybydaythereafter.Therateofotherintraoperativeadverseevents(eg,bleeding),aswell
as30and90daymortalityrates,werelowerinpatientswhounderwentsurgeryonthefirstorseconddayafter
admissionthaneitheronthedayofadmissionoraftertheseconddayafteradmission.Theauthorsofthestudy
advocatedoperatingwithintwodaysofadmission,butafterpatientshavebeenadequatelyresuscitated,and
whenthemostqualifiedsurgeonbecomesavailable.Althoughtherewerenodata,theyspeculatedthatthe
slightlyhigherrateofnonbiliaryadverseeventsthatoccurredwhenpatientsunderwentsurgeryonthedayof
admissioncomparedwiththedayafterwereduetounderresuscitationofthepatientoralackoflaparoscopic
surgicalexpertise.

Earlysurgeryisalsoeasiertoperform,aslocalinflammationincreases72hoursaftertheinitialonsetof
symptoms,makingdissectionlessprecise,increasingtheseverityofsurgicalcomplications,andmakingopen
conversionmorelikely.

Nevertheless,therearedatatosuggestthatsurgeryisstillsafeevenafter72hoursofsymptomonset,albeitwith
ahigherrateofconversionfromlaparoscopictoopentechnique[27,3335].Inarandomizedtrialof86patients
withacutecholecystitiswhohadmorethan72hoursofsymptoms,earlylaparoscopiccholecystectomyduringthe
indexadmissionwassafe[36].Of42patientswhoreceivedearlysurgery,onlyonerequiredconversiontoopen
surgerynonehadabileleakorbileductinjury.Comparedwithsurgerydelayedforsixweeks,earlysurgery
reducedtheoverallmorbidityratefrom39to14percent.Giventhatthepostoperativecomplicationrates(15
percentearlyversus17percentdelayed)weresimilar,thedifferenceinmorbiditywasalmostentirelyaccounted
forbymorbiditiesthatoccurredduringthewaitingperiodinpatientswhowerewaitingfordelayedsurgery(3
failedinitialtreatment10requiredunplannedreadmissionwhileawaitingsurgery).Thelengthofstay(fourversus
sevendays),durationofantibiotictherapy(2versus10days),andtotalhospitalcost(9349versus12,361)
werealsoinfavorofearlysurgery.Theauthorsofthistrialarguedthatthedegreeofinflammatorychanges
associatedwithacutecholecystitismaynotbetimedependentaspreviouslythought[37]andtherefore
suggestedearlylaparoscopiccholecystectomymaybeofferedtopatientswithacutecholecystitisregardlessof
thedurationofsymptoms.

SurgicalapproachLaparoscopiccholecystectomyisconsideredthestandardapproachforthesurgical
treatmentofacutecalculouscholecystitis.Comparedwithopencholecystectomy,laparoscopiccholecystectomy
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reducespostoperativepainandsignificantlyshortenshospitallengthofstayandconvalescence,andtimeaway
fromwork,andispreferredbymanypatientsfromacosmeticviewpoint[3844].However,theoverallserious
complicationrateinlaparoscopiccholecystectomyremainshigherthanthatseenwithopencholecystectomy
thus,thethresholdforconversiontoanopenprocedureshouldbelow[45,46].Factorswhichmayleadthe
surgeontoprimarilychoose,orconvertto,anopenapproacharediscussedindetailelsewhere.(See"Open
cholecystectomy",sectionon'Indicationsforopensurgery'and"Laparoscopiccholecystectomy",sectionon
'Intraoperativecomplications'.)

Althoughothertechniquessuchassingleincisionlaparoscopy,minilaparoscopy,roboticassistedlaparoscopy,
andnaturalorificetransluminalendoscopicsurgery(NOTES)havebeenusedtotreatpatientswithsymptomatic
cholelithiasis,theirroleinthetreatmentofpatientswithacutecholecystitisislimitedduetothetechnically
demandingdissectioncausedbysevereinflammationaswellastechnicalchallengesassociatedwiththe
adoptionofthesenewtechnologies[47].(See"Laparoscopiccholecystectomy",sectionon'Abdominalaccess'.)

Forselectedpatientsinwhomtheriskforinjuryorexcessivebloodlossisdeemedtoohightoperform
cholecystectomy,acholecystostomyorasubtotalcholecystectomycanbeperformed.Thelatterprocedure
achievescontrolofthecysticductattheleveloftheneckofthegallbladderandleavesthedomeofthe
gallbladderadherenttotheliverfossainsitu[48,49].Biliaryleakscanstilloccur,butthesecangenerallybe
managedconservatively.(See"Laparoscopiccholecystectomy"and"Complicationsoflaparoscopic
cholecystectomy"and"Repairofcommonbileductinjuries".)

HIGHRISKPATIENTSPatientscategorizedasASAclassesIII,IV,orV,haveperioperativemortalityrates
rangingfrom5to27percent,andareconsideredhighriskforcholecystectomy(table2)[17].

Forthesepatients,theriskofcholecystectomylikelyoutweighsthepotentialbenefits,andaninitialnonoperative
approachshouldbeundertakenthatincludesantibiotictherapyandbowelrest.Forthosewhofailtoimprove,
gallbladderdrainageshouldbeimplementedwiththeeventualgoalofperformingcholecystectomy.Once
cholecystitisresolves,thepatientsriskforsurgeryshouldbereassessed.Patientswhohavebecomereasonable
candidatesforsurgeryshouldundergoelectivecholecystectomy[50].Medicalmanagementwithinterval
cholecystectomyonlyforrecurrentacutecholecystitismaybeappropriateinsomepatients[51].

However,aninitialsurgicalapproachmaybepreferredinsomehighriskpatients(eg,gangrenousor
emphysematouscholecystitis)forwhomtheburdenoftheongoingsystemiceffectsofcholecystitisisdeemedto
begreaterthantheriskofsurgery.Inastudyof483patientsundergoingcholecystectomyforacutecholecystitis,
gangrenouscholecystitiswasfoundin24(5percent)[52].Patientswithgangrenousgallbladdershadamuch
highermortalityratethanpatientswhohadinflamedbutnongangrenousgallbladders(12.5versus0.9percent).
Inthesamestudy,gallbladdergangrenewasassociatedwithanolderage,malesex,andahigherpreoperative
bilirubinlevel,aswellascomorbidmedicalconditionssuchasdiabetes,coronaryarterydisease,andsystemic
inflammatoryresponsesyndrome.

AntibiotictherapyForhighriskpatients,theinitialapproachshouldincludeantibiotictherapyandbowelrest,
followedbyeithercholecystectomyforthosewhoimproveorgallbladderdrainageforthosewhofailtoimprove.
(See'Antibiotics'above.)

Percutaneouscholecystostomyisindicatedinpatientswhofailaninitialtrialofantibiotictherapy.Inatrialof123
highriskpatientswithacutecholecystitiswhowererandomlyassignedtopercutaneouscholecystostomyor
antibiotictherapy,asimilarpercentageofpatientsineachgrouphadresolutionoftheirsymptoms(86versus87
percent).Allsuccessfullytreatedpatientsshowedclinicalimprovementwithinthefirstthreedays[53],supporting
theuseofantibioticsasinitialtherapyofcholecystitisinhighriskpatients.However,gallbladderdrainageby
percutaneouscholecystostomyinconjunctionwithantibioticsmaybethebestinitialtreatmentforveryillpatients
(ie,intensivecareunit)[5457].
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GallbladderdrainageSomeformofgallbladderdrainageisrequiredforhighriskpatientsmanaged
conservativelybutwhoshownoappreciableimprovementandprogresstoseveresymptoms.Thegoalof
drainageistodirectpurulentmaterialawayfromtheobstructedgallbladder,whichalsoallowsforresolutionof
edema,whichoftenopensuptheobstructedcysticduct.

Gallbladderdrainagecanbeaccomplishedviapercutaneous,endoscopic,orsurgicalapproaches.Inone
retrospectivereviewof185patients,78percentweretreatedwithpercutaneouscholecystostomy,and22percent
withatubeplacedsurgically[58].Overhalfthepatients(57percent)subsequentlyunderwentlaparoscopic
cholecystectomy.Regardlessofcholecystostomytubeapproach,surgicalorpercutaneous,therewereno
differencesintheproportionofpatientswhounderwentlaparoscopiccholecystectomyasdefinitivetreatment.

PercutaneousPercutaneouscholecystostomyisindicatedforpatientswithacutecholecystitiswhohave
[47]:

Contraindicationstogeneralanesthesia
Severecholecystitis
Latepresentation(>72hoursafteronsetofsymptoms)
Failureofmedical(antibiotic)therapy

Percutaneouscholecystostomyresolvesacutecholecystitisinapproximately90percentofpatients.
Decompressingthegallbladderallowsbothlocalinflammationandsystemicillnesstoresolve,beforegallbladder
removalcouldbeaccomplishedwithlessrisktothepatient.Thetimingofcholecystectomyaftergallbladder
drainagecanbevariable,rangingfromimmediatelyafterclinicalimprovementtoaftereightweeks.Wetypically
performcholecystectomypriortothreedaysfromtheonsetofsymptomsoraftersixweeksotherwise.However,
somepatientsbenefitfromcholecystectomywithintheseboundarieswhentheirclinicalsituationdictates
necessitytoproceedinordertoacceleratedeliveryofcare.

Inarandomizedtrialcomparingpercutaneouscholecystostomyfollowedbyearly(withinsixdays)laparoscopic
cholecystectomyversusantibiotictherapyfollowedbydelayed(aftereightweeks)laparoscopiccholecystectomy
in70highriskpatientswithacutecholecystitis,patientswhoreceivedpercutaneouscholecystostomyrecovered
soonerwithashortermeanhospitalstay(5versus15days)andlowercost($2612versus$3735)[59].All
patientsinthepercutaneouscholecystostomygroupexperiencedsymptomaticreliefwithin24hoursafter
catheterplacement,whereaspatientsintheantibioticgroupimprovedwithin48to72hours.Inaddition,at
subsequentcholecystectomy,therewasalowerconversionratefromlaparoscopictoopencholecystectomyin
thepercutaneouscholecystostomygroup(6versus13percent).

Inaprospectivestudyof91highriskpatientswithacutecholecystitis,patientswerenonrandomlyassignedto
eitheremergencylaparoscopiccholecystectomyorpercutaneouscholecystostomyfollowedbydelayed
cholecystectomyafterfourweeks[60].Patientsinthecholecystostomygrouphadalowerfrequencyof
conversiontoopensurgery(8versus19percent),alowerriskofintraoperativebleeding>100mL(9versus33
percent),ashortermeanhospitalstay(3versus5.3days),andalowerriskofcomplications(9versus35
percent)[60].Similarfindingswerereachedbyretrospectivestudies[6163].

Inretrospectivestudies,highermortalityandmorbidityrateshaveoftenbeenassociatedwithpercutaneous
cholecystostomytreatmentofacutecholecystitiscomparedwithcholecystectomy.Asanexample,inone
retrospectivereviewthatincluded1918patients,30daymortalityafterpercutaneouscholecystostomywas15.4
percent,butonly4.5percentforcholecystectomy[64].Thisdifferenceislikelyduetopatientselectionbias,asthe
healthiestcohortisselectedbysurgeonsforsurgicalmanagement.Patientswhounderwentpercutaneous
cholecystostomywereusuallyolder,andhadahigherASAclassification,morecomorbidities,longerhospital
stay,morecomplications,andmorereadmissions.Inonetimecohortstudy,the30daymortalityratedecreased
from36to12percentwhenmorehealthypatients(ASAclassIandII:0versus18percent)underwentthe
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percutaneouscholecystostomyprocedurebetween1998and2009,comparedwiththetimeperiodfrom1989to
1998[65].Arandomizedprospectivetrialcomparingpercutaneouscholecystostomywithcholecystectomy
treatmentofacutecholecystitisinhighsurgicalriskpatientsisunderway[66].

Thetechnicalsuccessofpercutaneouscholecystostomyrangesfrom82to100percentinvariousseries[5457].
Inaretrospectivereview,theoutcomesof106patientswithacutecholecystitis(calculousandacalculous)treated
bypercutaneouscholecystostomywereevaluatedovera10yearperiod67percentpresentedtotheemergency
roomand23percentwereinpatientsadmittedinitiallyforotherconditions[67].Abouthalfineachgrouphad
gallstones.Aftercholecystostomytubeplacement,clinicalimprovementwasseenoverallin68percent,whereas
32percentshowednoimprovementorclinicallyworsened.Morepatientswhopresentedtotheemergency
departmentprimarilywithacutecholecystitisshowedimprovementcomparedwiththeinpatients(84versus34
percent).

Minorcomplicationsofpercutaneousdrainageincludebleeding,catheterblockageanddislodgement(10to15
percent),andfailuretoresolvetheacutecholecystitis(10percent)[55,57,68].Inonestudy,majorbleeding
complicationsoccurredrarely(0.4percent)andwerenodifferentbetweenpatientswithandwithoutcoagulopathy
[68].Failureisusuallyrelatedtoineffectivedrainageduetothicksludgeorpus.Wegenerallyirrigatethe
gallbladdercontentsmanuallywithnormalsalinethroughthecatheter.Ifirrigationisineffective,thepercutaneous
pigtailcathetercanbereplacedoverawirewithalargeronetoachievemoreeffectiveirrigation.

Percutaneouscholecystostomyisoftenperformedwiththeintentofdelayedcholecystectomyhowever,many
patientsdonotactuallygoontoreceivecholecystectomyduetoongoingcontraindications[58,69].Patientswho
stabilizebutcontinuetobehighriskforsurgerycanbeconsideredforpercutaneousgallstoneextractionwithor
withoutmechanicallithotripsy[70].

EndoscopicEndoscopicgallbladderdrainagecanbeperformedinpatientswithacutecholecystitisin
whompercutaneousapproachesarecontraindicated,orarenotanatomicallyfeasible(ie,advancedliverdisease,
ascites,orcoagulopathy)[47,71,72].Twodifferenttechniques,transpapillarydrainageortransmuraldrainageare
available,dependingonlocalexpertise[47].

TranspapillarydrainageTranspapillarydrainageutilizesendoscopicretrogradecholangiography
(ERCP)techniquesandequipmenttoplaceadrainagecatheterintothegallbladderviathecysticduct.Theother
endofthecatheteriseitherbroughtoutthroughthenose(nasobiliarydrain)orlefttodraininternallyintothe
duodenum.

Whentechnicallysuccessful(inabout76to94percentofpatients),transpapillarydrainageresolvesacute
cholecystitisin80to90percentofpatients,includingthosewithadvancedlivercirrhosis[7375].However,this
techniquecanbetechnicallychallengingbecausethecysticductisoftennarrowandtortuous.Inaddition,this
procedurehasalltheinherentandoccasionallyseriouscomplicationsassociatedwithendoscopicretrograde
cholangiography(eg,postsphincterotomybleeding)(see"Endoscopicretrogradecholangiopancreatography:
Indications,patientpreparation,andcomplications").

TransmuraldrainageTransmuraldrainageutilizesendoscopicultrasoundguidancetoaccessthe
inflamedgallbladderwithaneedlepuncture,followedbydilationandstentplacementoveraguidewire.The
introductionofselfexpandable,covered,lumenapposingmetalstentsallowsdirectendoscopicaccesstothe
gallbladderfordecompressionandstoneremoval.Thetransmuraldrainagetechniqueistechnicallysuccessfulin
mostcases(97percent)andresolvesacutecholecystitisinover95percentofpatients[76].

Inarandomizedtrialinvolving59patientswithacutecholecystitis,whodidnotrespondtoinitialmedical
managementandwerenotsurgicalcandidates,transmuraldrainagewasaseffectiveaspercutaneousdrainage
ofthegallbladderintermsoftechnical(97versus97percent)andclinicalsuccessrates(100versus96percent)

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[77].Similarproportionsofpatientsineachgroupdevelopedcomplications(7versus3percent)andrequired
conversiontoopensurgerywhentheyeventuallyunderwentlaparoscopicgallbladdersurgery(9versus12
percent).Postprocedurepainwassignificantlylessinthetransmuraldrainagegroup.

Endoscopictransmuraldrainageisusedasabridgetodefinitivegallbladdersurgery.However,theadhesion
createdbetweenthegallbladderandduodenum/stomachmayinterferewithfuturecholecystectomysurgery.

SurgicalAlthoughhighriskpatientsaregenerallytreatedwithantibiotictherapywithorwithouta
gallbladderdrainageprocedure,aninitialsurgicalapproachmaybepreferredinsomepatientsforwhomthe
burdenoftheongoingsystemiceffectsofcholecystitisisdeemedtobegreaterthantheriskofsurgery.If
cholecystectomyisnotfeasible,asubtotalcholecystectomycanbeperformedinstead,butifmedicalrisk
precludesgallbladderremoval,asurgicalcholecystostomytubecanbeinsertedthroughalimitedlaparotomyin
theoperatingroom,oratthebedsideintheintensivecareunitsetting,ifnecessary.(See"Open
cholecystectomy",sectionon'Opencholecystostomytubeplacement'.)

SubsequentcarefollowingdrainageForpatientswhoundergogallbladderdrainage,theapproachto
subsequentcaredependsonwhetherclinicalsymptomsresolveaftergallbladderdrainagehasbeen
accomplished.

EffectivedrainageTheriskforsurgeryshouldbereconsideredoncecholecystitisresolvesinpatients
treatedconservativelywithantibioticsandgallbladderdrainage.Patientswhohavebecomereasonable
candidatesforsurgeryshouldundergoelectivecholecystectomy.Laparoscopiccholecystectomymaybethe
preferredtreatmentinhighriskpatientswhorequiresurgery.(See"Laparoscopiccholecystectomy".)

IneffectivedrainageAsurgicalapproachmaybecomenecessaryifthelessinvasivetechniques
discussedabovearenottechnicallyfeasible,areunsuccessfulatprovidingadequatedrainage,orifthepatient
doesnotimprovefollowingdrainage,whichsuggeststhatthegallbladdermayhaveprogressedtogangrene.In
thissetting,laparoscopiccholecystectomyispreferredbutconversiontoopensurgerymaybenecessary.(See
"Laparoscopiccholecystectomy"and"Opencholecystectomy".)

MORBIDITYANDMORTALITYTheoverallmortalityofasingleepisodeofacutecholecystitisisapproximately
3percent.However,theriskinagivenpatientdependsuponthepatient'shealthandsurgicalrisk[55].Mortality
islessthan1percentinyoung,otherwisehealthypatients,butapproaches10percentinhighriskpatients,orin
thosewithcomplications.Perioperativemorbidityandmortalityassociatedwithspecifictreatmentsarereviewed
elsewhere.(See"Opencholecystectomy",sectionon'Perioperativemorbidityandmortality'and"Laparoscopic
cholecystectomy",sectionon'Postoperativecomplications'.)

AstudyoftheAmericanCollegeofSurgeonsNationalSurgicalQualityImprovementProgram(NSQIP)database
evaluatedoutcomesfollowingtreatmentofacutecholecystitisin5460patientswithandwithoutdiabetes[78].
Mortalityamong770patientswithdiabeteswassignificantlyhigherthaninthe4690patientswithoutdiabetes(4.4
versus1.4percent).Theriskforcomplicationsincludingcardiovasculareventsandrenalfailurewasalso
significantlyincreased.

PreventionofrecurrentgallstonesFollowingcholecystectomy,orothernonsurgicalmeanstoremove
gallstones,patientswhoremainathighriskfordevelopingrecurrentgallstonesmaybenefitfromcertainmedical
therapies.Thesearediscussedelsewhere.(See"Patientselectionforthenonsurgicaltreatmentofgallstone
disease",sectionon'Prophylaxisinpatientsathighriskfordevelopingsymptomaticgallstonedisease'.)

SUMMARYANDRECOMMENDATIONS

Acutecholecystitisreferstoasyndromeofrightupperquadrantpain,fever,andleukocytosisassociatedwith
gallbladderinflammation,whichisusuallyrelatedtogallstonedisease.Onceapatientdevelopsacute
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cholecystitis,definitivetherapyaimedateliminatingthegallstonesisrecommended.Withoutdefinitive
therapy,thelikelihoodofrecurrentsymptomsorcomplicationsishigh.(See'Introduction'aboveand
'Overviewoftreatment'above.)

Patientsdiagnosedwithacutecholecystitisshouldbeadmittedtothehospital.Initialsupportivecareincludes
intravenousfluidtherapy,correctionofelectrolytedisorders,andcontrolofpain.Adequatepaincontrolcan
usuallybeachievedwithnonsteroidalantiinflammatorydrugs(NSAIDs)oropioids.Patientsshouldbekept
fastingandthosewhoarevomitingmayneedplacementofanasogastrictube.(See'Supportivecare'
above.)

Acutecholecystitisisprimarilyaninflammatoryprocess,butsecondaryinfectionofthegallbladdercanoccur
asaresultofcysticductobstructionandbilestasis.Manycliniciansroutinelyadministerantimicrobialtherapy
toallpatientsdiagnosedwithacutecholecystitis,whicharecontinueduntilthegallbladderisremovedorthe
cholecystitisclinicallyresolves.Ifsepsisissuspected(laboratoryorclinicalfindings),orradiographicfindings
areindicativeofgallbladderischemiaornecrosis,wesuggestempiricantibiotictherapy(Grade2C).
Antibioticoptionsanddosesareprovidedinthetable(table3).Forpatientswithuncomplicatedcholecystitis,
wediscontinueantibioticsthedayafterthecholecystectomy.(See'Antibiotics'above.)

Thechoiceandtimingofinterventionforacutecholecystitis(cholecystectomy,gallbladderdrainage)depends
upontheseverityofsymptomsandthepatient'soverallriskofsurgery.Drainageoptionsinclude
percutaneousoropencholecystostomyandendoscopictranspapillaryortransmuraldrainage.

Emergentinterventionisindicatedforpatientswith:

Progressivesymptomsandsignssuchashighfever,hemodynamicinstability,orintractablepainin
spiteofadequatepainmedication.

Suspicionofgallbladdergangreneorgallbladderperforation

Forpatientswithoutemergentindicationsfordefinitivetherapywhoarelowriskforsurgery,we
recommendcholecystectomyduringtheinitialhospitalization(Grade1A).Cholecystectomyperformed
earlyratherthanlaterinthehospitalizationmaybeassociatedwithreducedperioperativemorbidityand
mortality.Lowriskpatientsgenerallyundergolaparoscopiccholecystectomy.Comparedwithopen
cholecystectomy,laparoscopiccholecystectomyreducespostoperativepainandsignificantlyshortens
thelengthofhospitalstayandconvalescence.(See'Timingofcholecystectomy'aboveand'Lowrisk
patients'above.)

Forpatientswithoutemergentindicationsfordefinitivetherapy,andinwhomtheriskofcholecystectomy
outweighsthepotentialbenefits,gallbladderdrainagewithpercutaneouscholecystostomyoroneofthe
endoscopicdrainageproceduresisindicatedifsymptomsdonotimprovewithsupportivecare.Once
cholecystitisresolves,thepatientsriskforsurgeryshouldbereassessed.Patientswhohavebecome
reasonablecandidatesforsurgeryshouldundergoelectivecholecystectomy.Patientswhostabilizewith
gallbladderdrainagebutcontinuetobeathighriskforsurgerycanbeconsideredforpercutaneous
gallstoneextractionwithorwithoutmechanicallithotripsy.(See'Gallbladderdrainage'above.)

Mortalityassociatedwithasingleepisodeofacutecholecystitisdependsuponthepatient'shealthand
surgicalrisk.Overallmortalityisapproximately3percent,butislessthan1percentinyoung,otherwise
healthypatients,andapproaches10percentinhighriskpatients,orinthosewithcomplications.

UseofUpToDateissubjecttotheSubscriptionandLicenseAgreement.

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Topic3684Version35.0

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GRAPHICS

Treatmentofacutecholecystitis

CourtesyofSalamZakko,MD,FACP.

Graphic64526Version3.0

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Rupturedgallbladderwithbiloma

AxialCTscanoftheupperabdomenwithoutintravenousbutwithoralcontrast
demonstratesarupturedgallbladderwithacollectionofbile(biloma)inthegallbladder
fossa.Notethattherearemultiplegallstonesthatarelocatedoutsideofthegallbladder.
Thereisalsoasmallamountoffluidaroundtheliver.

CT:computedtomography.

CourtesyofJPierreSasson,MD.

Graphic74614Version4.0

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Empiricantibiotictreatmentofacutecholecystitis

Infection Regimen

Communityacquiredacutecholecystitisofmildto Cefazolin,cefuroxime,orceftriaxone.
moderateseverity

Communityacquiredacutecholecystitisofsevere Imipenemcilastatin,meropenem,doripenem,piperacillin
physiologicdisturbance,advancedage,or tazobactam,ciprofloxacinplusmetronidazole,levofloxacin
immunocompromisedstate plusmetronidazole,orcefepimeplusmetronidazole.*

Healthcareassociatedbiliaryinfectionofanyseverity Imipenemcilastatin,meropenem,doripenem,piperacillin
tazobactam,ciprofloxacinplusmetronidazole,levofloxacin
plusmetronidazole,orcefepimeplusmetronidazole,with
vancomycinaddedtoeachregimen.*

*BecauseofincreasingresistanceofEscherichiacolitofluoroquinolones,localpopulationsusceptibilityprofilesand,if
available,isolatesusceptibilityshouldbereviewed.

Reproducedfrom:SolomkinJS,MazuskiJE,BradleyJS,etal.Diagnosisandmanagementofcomplicatedintraabdominal
infectioninadultsandchildren:GuidelinesbytheSurgicalInfectionSocietyandtheInfectiousDiseasesSocietyofAmerica.
CID201050(2):13364,bypermissionofOxfordUniversityPressonbehalfofTheInfectiousDiseasesSocietyofAmerica.

Graphic108360Version1.0

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AmericanSocietyofAnesthesiologists(ASA)PhysicalStatusClassificationSystem

ASA1 Anormalhealthypatient

ASA2 Apatientwithmildsystemicdisease

ASA3 Apatientwithseveresystemicdisease

ASA4 Apatientwithseveresystemicdiseasethatisaconstantthreattolife

ASA5 Amoribundpatientwhoisnotexpectedtosurvivewithouttheoperation

ASA6 Adeclaredbraindeadpatientwhoseorgansarebeingremovedfordonorpurposes

ASAPhysicalStatusClassificationSystemisreprintedwithpermissionoftheAmericanSocietyofAnesthesiologists,520N.
NorthwestHighway,ParkRidge,Illinois600682573.

Graphic87504Version6.0

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Empiricantibiotictherapyforgramnegativeandanaerobicpathogens

Regimen Dose(adult)*

Firstchoice

Monotherapywithabetalactam/betalactamaseinhibitor:
Ampicillinsulbactam 3gIVeverysixhours
Piperacillintazobactam 3.375or4.5gIVeverysixhours
Ticarcillinclavulanate 3.1gIVeveryfourhours

CombinationthirdgenerationcephalosporinPLUSmetronidazole:
Ceftriaxoneplus 1gIVevery24hoursor2gIVevery12hoursforCNSinfections
Metronidazole 500mgIVeveryeighthours

Alternativeempiricregimens

Combinationfluoroquinolone PLUSmetronidazole:
Ciprofloxacinor 400mgIVevery12hours
Levofloxacinplus 500or750mgIVoncedaily
Metronidazole 500mgIVeveryeighthours

Monotherapywithacarbapenem :
Imipenemcilastatin 500mgIVeverysixhours
Meropenem 1gIVeveryeighthours
Doripenem 500mgIVeveryeighthours
Ertapenem 1gIVoncedaily

*Antibioticdosesshouldbeadjustedappropriatelyforpatientswithrenalinsufficiencyorotherdoserelatedconsideration.
EcoliresistancetoAmpicillinsulbactamisemerginginsomeareaschecklocalsusceptibilitydata.
Somecliniciansuse4.5geveryeighthoursforempirictherapysincethepercenttimeabovetheMICissimilarbetween
theregimensformostpathogenshowever,thisregimenisNOTrecommendedfornosocomialpneumoniaorPseudomonas
coverage.PleaserefertoUpToDatetopicsonthe"Treatmentofhospitalacquired,ventilatorassociated,andhealthcare
associatedpneumoniainadults"and"TreatmentofPseudomonasaeruginosainfections".
Fluoroquinolonesaregenerallyavoidedinpregnantwomenduetopotentialfetaltoxicity.
Usecarbapenemscautiouslyinpatientswithimmediatetypehypersensitivitytobetalactams.
ErtapenemlacksactivityagainstAcinetobacterandPseudomonasandisnotanappropriatechoiceforsevereor
nosocomialinfection.

Graphic67894Version15.0

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2017525 TreatmentofacutecalculouscholecystitisUpToDate

ContributorDisclosures
CharlesMVollmer,Jr,MD Nothingtodisclose SalamFZakko,MD,FACP Nothingtodisclose NezamH
Afdhal,MD,FRCPI Grant/Research/ClinicalTrialSupport:AbbVieBMSGilead[HCVStudies].
Consultant/AdvisoryBoards:AbbVieEchosensGileadSciencesGlaxoSmithKlineJannsenPharmaceutica
LigandMerck&CoNovartisInternationalAGSpringBankPharmaceuticalsTRIOHealthCare[LiverDisease].
EquityOwnership/StockOptions:SpringBankPharmaceuticals[HBV,RSV].EmploymentSpringBank
Pharmaceuticals[HBV,RSV]Norelevantconflictontopic. StanleyWAshley,MD Nothingto
disclose WenliangChen,MD,PhD Nothingtodisclose

Contributordisclosuresarereviewedforconflictsofinterestbytheeditorialgroup.Whenfound,theseare
addressedbyvettingthroughamultilevelreviewprocess,andthroughrequirementsforreferencestobe
providedtosupportthecontent.Appropriatelyreferencedcontentisrequiredofallauthorsandmustconformto
UpToDatestandardsofevidence.

Conflictofinterestpolicy

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