拯救脓毒症患者行动国际严重脓毒症和脓毒性休克2014 课件

SurvivingSepsisCampaignGuidelinesforManagementofSevereSepsisandSepticShock

SlidePresentationsSprungCL,AngusDC,AnnaneD,CarcilloJA,DeutschmanCS,GerlachH,JaeschkeR,KleinpellRM,MachadoFR,OpalS,RubenfeldG,SevranskyJ,TownsendSR,DellingerRP.DellingerRPetal.CritCareMed.2013;41:580-637.DellingerRPetal.IntensiveCareMed.2013;39:165-228.Copyright2014SCCM/ESICMSurvivingSepsisCampaignGuidSSC2012Guidelines

SlidePresentations

1.

GradingofRecommendations:G.Rubenfeld2.

InitialResuscitation:D.Annane3.

Infection-RelatedIssues:S.Opal4.

AdjunctiveTherapy:H.Gerlach5.

MechanicalVentilation:J.Sevransky6.

GlucoseControl,BicarbonateTherapy:C.Sprung.Slide2Copyright2014SCCM/ESICMSSC2012Guidelines

SlidePreSSC2012Guidelines

SlidePresentations

7.

Nutrition:F.Machado,D.Angus8.

RenalReplacementTherapy:S.Townsend9.

ProphylaxisforVenousThromboembolism(VTE):C.Deutschman10.

StressUlcerProphylaxis(SUP):R.Jaeschke11.

SettingGoalsofCare:R.Kleinpell12.

PediatricConsiderations:J.CarcilloSlide3Copyright2014SCCM/ESICMSSC2012Guidelines

SlidePreSSC2012Guidelines

GradingofRecommendationsAssessment,Development,andEvaluation(GRADE)MethodologyG.RubenfeldSlide4Copyright2014SCCM/ESICMSSC2012Guidelines

GradingGradingofRecommendationsAssessment,Development,andEvaluation(GRADE)MethodologyQualityofEvidenceSlide5Copyright2014SCCM/ESICMGradingofRecommendationsAssDowngradingandUpgrading

QualityofEvidenceRCTPoorqualityofplanningandimplementationInconsistencyofresultsIndirectnessofevidenceImprecisionofresultsHighlikelihoodofreportingbias.ObservationalStudiesStartwitha“lowquality”ratingMagnitudeoftheeffectisverylargeorlargeDose-responserelationshipAllplausiblebiaseswoulddecreasethemagnitudeofanapparenttreatmenteffectSlide6Copyright2014SCCM/ESICMDowngradingandUpgrading

QuaStrengthofRecommendationStrongRecommendWhenvirtuallyallinformedpatientswouldchoosethesamemanagementstrategyWeak(conditional)SuggestImplythatchoiceswilldifferacrosstherangeofpatientvaluesandpreferencesSlide7Copyright2014SCCM/ESICMStrengthofRecommendationStroFactorsThatInfluenceStrengthofRecommendationSlide8Copyright2014SCCM/ESICMFactorsThatInfluenceStrengtSSC2012Guidelines

InitialResuscitationHemodynamicSupportD.AnnaneInitialResuscitationFluidTherapyVasopressorTherapyInotropicTherapyCopyright2014SCCM/ESICMSSC2012Guidelines

Initial

InitialResuscitationWerecommendtheprotocolized,quantitativeresuscitationofpatientswithsepsis-inducedtissuehypoperfusion(definedashypotensionpersistingafterinitialfluidchallengeorlactate≥4mmol/L).ThisprotocolshouldbeinitiatedassoonashypoperfusionisrecognizedandshouldnotbedelayedpendingICUadmission.Slide10Copyright2014SCCM/ESICMInitialResuscitationWerecomInitialResuscitationDuringthefirst6hours,thegoalsofinitialresuscitationofsepsis-inducedhypoperfusionshouldincludeallofthefollowingasapartofatreatmentprotocol(Grade1C):

Centralvenouspressure8-12mmHgMeanarterialpressure≥65mmHgUrineoutput≥0.5mL/kg/hCentralvenous(superiorvenacava)ormixedvenousoxygensaturation70%or65%,respectivelySlide11Copyright2014SCCM/ESICMInitialResuscitationDuringtInitialResuscitationOnerandomizedsingle-centertrialdemonstratedreducedmortalitywithearlyquantitativeresuscitationforemergencydepartmentpatientspresentingwithsepticshock.

RiversE.NEnglJMed.2001;345:1368-1377.Secondmulticenterrandomizedtrialof314patientswithseveresepsisin8Chinesecentersreporteda17.7%absolutereductionin28-daymortality(survivalrates,75.2%vs.57.5%,P=0.001).

EGDTCollaborativeGroupofZhejiangProvince. ZhongguoWeiZhongBingJiJiuYiXue.2010;6:331-334.Slide12Copyright2014SCCM/ESICMInitialResuscitationOnerandoEarlyGoal-DirectedTherapyintheTreatmentofSevereSepsisandSepticShockControlEGDTRelativeRisk(95%ConfidenceInterval)

P

In-Hospital46.530.50.58(0.38-0.87)0.00928-dayMortality8(0.39–0.87)0.0160-dayMortality56.944.30.67(0.46-0.96)0.03RiversE.NEnglJMed.2001;345:

1368-1377.Slide13Copyright2014SCCM/ESICMEarlyGoal-DirectedTherapyin

InitialResuscitationWesuggest,inpatientswithelevatedlactatelevelsasamarkeroftissuehypoperfusion,targetingresuscitationtonormalizelactateasrapidlyaspossible.(Grade2C)

Slide14Copyright2014SCCM/ESICMInitialResuscitationWesuggeInitialResuscitationOnemulticenterrandomizedtrialdemonstratedthatearlyquantitativeresuscitationbasedonlactateclearance(decreasebyatleast10%)wasnon-inferiortoresuscitationbasedonachievingScvO2of70%ormore.

JonesA.JAMA.2010;303:739–746.Asecondmulticenterrandomizedtrialdemonstratedthatastrategybasedon>20%decreaseinlactatelevelsper2hoursofthefirst8hours,inadditiontoachievementofanScvO2

target,wasassociatedwitha9.6%absolutereductioninmortality.

JansenTC.AmJRespirCritCareMed.2010;182:752–761.Slide15Copyright2014SCCM/ESICMInitialResuscitationOnemultiLactateClearancevsCentralVenousOxygenSaturationasGoalsofEarlySepsisTherapy:MortalityJonesA.JAMA.2010;303:739–746.Slide16Copyright2014SCCM/ESICMLactateClearancevsCentralVEarlyLactate-GuidedTherapyinIntensiveCareUnitPatientsJansenTC.AmJRespirCritCareMed.2010;182:752–761.adjustedHR=0.61;95%CI,0.43-0.87;P=0.006Slide17Copyright2014SCCM/ESICMEarlyLactate-GuidedTherapyi

FluidTherapyWerecommendcrystalloidsbeusedastheinitialfluidofchoiceintheresuscitationofseveresepsisandsepticshock.

(Grade1B)Werecommendagainsttheuseofhydroxy-ethylstarchesforfluidresuscitationofseveresepsisandsepticshock.(Grade1B)

Slide18Copyright2014SCCM/ESICMFluidTherapyWerecommendcry

FluidTherapy-MortalityThreemulticenterrandomizedtrialsshowednosignificantdifferenceinmortalitybetweencrystalloidsandhydroxyethylstarches.

BrunkhorstF.NEnglJMed.2008;358:125-139.

GuidetB.CritCare.2012;16:R94.

MyburghJA.NEnglJMed.2012;367:1901-1911.OnemulticenterrandomizedtrialdemonstratedincreasedmortalityrateswithHES130/0.42fluidresuscitationcomparedtoRingeracetate(51%vs43%.P=0.03).

PernerA.NEnglJMed.2012;367:124-134.

Slide19Copyright2014SCCM/ESICMFluidTherapy-MortalityThreZarychanskiR.JAMA.2013;309:678-688.Meta-analysis:HESversusOtherFluidsMortalityRR,1.09;95%CI,1.02to1.17Slide20Copyright2014SCCM/ESICMZarychanskiR.JAMA.2013;309:

FluidTherapy-KidneyinjuryThreemulticenterrandomizedtrialsshowedasignificantincreaseintheriskofacutekidneyinjurywithhydroxyethylstarchascomparedwithcrystalloids.

BrunkhorstF.NEnglJMed.2008;358:125-139.

PernerA.NEnglJMed.2012;367:124-134.

MyburghJA.NEnglJMed.

2012;367:1901-1911.Onemulticenterrandomizedtrialdidnotfindanincreaseintheriskofacutekidneyinjurywithhydroxyethylstarchascomparedwithcrystalloids.

GuidetB.CritCare.2012;16:R94.Slide21Copyright2014SCCM/ESICMFluidTherapy-KidneyinjuryZarychanskiR.JAMA.2013;309:678-688.Meta-analysis:HESversusOtherFluidsRenalReplacementTherapySlide22Copyright2014SCCM/ESICMZarychanskiR.JAMA.2013;309:

FluidTherapyWesuggesttheuseofalbumininthefluidresuscitationofseveresepsisandsepticshockwhenpatientsrequirerepeatedbolusesofcrystalloids.(Grade2C)Slide23Copyright2014SCCM/ESICMFluidTherapyWesuggesttheuMeta-analysis:AlbuminversusOtherFluidsOutcomesIllustrativecomparativerisks(95%CI)Relativeeffect

(95%CI)No.Ofparticipants

(studies)Qualityoftheevidence

(GRADE)AssumedriskCorrespondingriskControlOtherfluids(maybecrystalloidorcolloid)Short-termmortalityStudypopulationRR0.84

(0.73to0.97)1683

(11studies)⊕⊕⊕⊝

moderate342per1000287per1000

(249to332)Short-termmortality(albuminvscrystalloids)444per1000377per1000

(324to440)RR0.85(0.73to0.98)1402(4studies)⊕⊕⊕⊝

moderate1Short-termmortality(albuminvsothercolloids)342per1000195per1000

(249to396)RR0.81(0.57to1.16)281(7studies)⊕⊕⊕⊝

moderate11Gradereducedforimprecision.Slide24Copyright2014SCCM/ESICMMeta-analysis:Albuminversus

FluidTherapyWerecommendaninitialfluidchallengeinpatientswithsepsis-inducedtissuehypoperfusionwithsuspicionofhypovolemiatoachieveaminimumof30mL/kgofcrystalloids(aportionofthismaybealbuminequivalent).Morerapidadministrationandgreateramountsoffluidmaybeneededinsomepatients.(Grade1C)

Slide25Copyright2014SCCM/ESICMFluidTherapyWerecommendan

FluidTherapyWerecommendthatafluidchallengetechniquebeappliedwhereinfluidadministrationiscontinuedaslongasthereishemodynamicimprovementeitherbasedondynamic(eg,changeinpulsepressure,strokevolumevariation)orstatic(eg,arterialpressure,heartrate)variables

(Ungraded).

Slide26Copyright2014SCCM/ESICMFluidTherapyWerecommendthaVasopressorTherapyWerecommendthatvasopressortherapyinitiallytargetameanarterialpressure(MAP)of65mmHg.(Grade1C)Werecommendnorepinephrineasthefirst-choicevasopressor.(Grade1B)

Slide27Copyright2014SCCM/ESICMVasopressorTherapyWerecommenMeta-analysisofNorepinephrineversusDopamine

OutcomesIllustrativecomparativerisks*(95%CI)Relativeeffect

(95%CI)No.ofparticipants

(studies)Qualityoftheevidence

(GRADE)AssumedriskCorrespondingriskDopamineNorepinephrineShort-termmortalityStudypopulationRR0.91

(0.83to0.99)2043

(6studies)⊕⊕⊕⊝

moderate1,2530per1000482per1000

(440to524)Seriousadverseevents-SupraventriculararrhythmiasStudypopulationRR0.47

(0.38to0.58)1931

(2studies)⊕⊕⊕⊝

moderate1,2229per100082per1000

(34to195)Seriousadverseevents-VentriculararrhythmiasStudypopulationRR0.35

(0.19to0.66)1931

(2studies)⊕⊕⊕⊝

moderate1,239per100015per1000

(8to27)*Theassumedriskisthemediancontrolgroupriskacrossstudies.Thecorrespondingrisk(andits95%confidenceinterval)isbasedontheassumedriskinthecomparisongroupandtherelativeeffectoftheintervention(andits95%CI).

CI:Confidenceinterval;RR:Riskratio;1Strongheterogeneityintheresults(Isquared=85%),howeverthisreflectsdegreeofeffect,notdirectionofeffect.Wehavedecidednottolowertheevidencequality.2EffectresultsinpartfromhypovolemicandcardiogenicshockpatientsinDeBacker,NEJM2010.Wehaveloweredthequalityofevidenceonelevelforindirectness.Slide28Copyright2014SCCM/ESICMMeta-analysisofNorepinephrin

VasopressorTherapyWesuggestepinephrine(addedtoandpotentiallysubstitutedfornorepinephrine)whenanadditionalagentisneededtomaintainadequatebloodpressure.(Grade2B)

Slide29Copyright2014SCCM/ESICMVasopressorTherapyWesuggestMeta-analysisofNorepinephrineversusEpinephrine

OutcomesIllustrativecomparativerisks

(95%CI)Relativeeffect

(95%CI)No.ofparticipants

(studies)Qualityoftheevidence

(GRADE)AssumedriskCorrespondingriskEpinephrineNorepinephrineShort-termmortalityStudypopulationRR0.96

(0.77to1.21)540

(4studies)⊕⊕⊕⊝

moderate1357per1000343per1000

(268to429)Seriousadverseevents-supraventriculararrhythmiasStudypopulationRR1.10

(0.62to1.96)330

(1study)⊕⊕⊝⊝

low1,2118per1000130per1000

(58to198)Seriousadverseevents-ventriculararrhythmiasStudypopulationRR0.64

(0.27to1.51)330

(1study)⊕⊕⊝⊝

low1,275per100048per1000

(-5to95)1Gradereducedforimprecision.2Outcomereportedonlyinoneoffourtrials.Slide30Copyright2014SCCM/ESICMMeta-analysisofNorepinephrin

VasopressorTherapyVasopressinupto0.03units/minutecanbeaddedtonorepinephrinewiththeintentofraisingMAPtotargetordecreasingnorepinephrinedosage.Low-dosevasopressinisnotrecommendedasthesingleinitialvasopressorfortreatmentofsepsis-inducedhypotension,andvasopressindoseshigherthan0.03-0.04units/minuteshouldbereservedforsalvagetherapy(failuretoachieveadequateMAPwithothervasopressoragents).

Slide31Copyright2014SCCM/ESICMVasopressorTherapyVasopressiMeta-analysisofNorepinephrineversusVasopressinOutcomesIllustrativecomparativerisks(95%CI)Relativeeffect

(95%CI)No.ofparticipants

(studies)Qualityoftheevidence

(GRADE)AssumedriskCorrespondingriskVasopressinNorepinephrineShort-termmortalityStudypopulationRR1.12(0.96to1.30)963

(7studies)⊕⊕⊝⊝

low1,2,3,4386per1000433per1000

(371to502)Seriousadverseevents-supraventriculararrhythmiasStudypopulationR.R7.25(2.30to22.90)116

(3studies)⊕⊕⊝⊝

low1,2,3,545per1000325per1000

(103to1000)Seriousadverseevents-ventriculararrhythmiasStudypopulationR.R0.78(0.27to2.22)801

(2studies)⊕⊕⊝⊝

low1,2,3,420per100015per1000

(5to43)Seriousadverseevents-strokeStudypopulationRR1.04(0.07to16.51)778

(1study)⊕⊕⊝⊝

low1,2,3,43per10003per1000

(0to42)Seriousadverseevents-acutecoronaryeventsStudypopulationR.R1.05(0.44to2.50)849

(3studies)⊕⊕⊝⊝

low1,2,3,423per100024per1000

(10to58)Seriousadverseevents-limbischemiaStudypopulationR.R0.54(0.25to1.19)826

(2studies)⊕⊕⊝⊝

low1,2,3,436per100019per1000

(-4to36)1Variationsintypeofmolecule(vasopressinvsterlipressin)andindose.

2Somestudieshavecomparedvasopressinwithnorepinephrine,andsomestudieshavecomparedvasopressinplusnorepinephrineversusnorepinephrine.

3Unclearriskofbiasinsomestudies(methodsforallocationconcealment,blinding).4Imprecisionwithwideconfidenceintervalsspanningharmandbenefit.5Imprecision.Only21events.Slide32Copyright2014SCCM/ESICMMeta-analysisofNorepinephrin

VasopressorTherapyWesuggestdopamineasanalternativevasopressoragenttonorepinephrineonlyinhighlyselectedpatients(eg,patientswithlowriskofarrhythmiasand/orlowheartrate).(Grade2C)Phenylephrineisnotrecommendedexceptincircumstanceswhere:norepinephrineisassociatedwithseriousarrhythmiascardiacoutputisknowntobehighandbloodpressurepersistentlylow,orassalvagetherapywhencombinedinotrope/vasopressordrugsandlow-dosevasopressinhavefailedtoachieveMAPtarget.

(Grade1C)

Slide33Copyright2014SCCM/ESICMVasopressorTherapyWesuggest

VasopressorTherapyWerecommendthatlow-dosedopaminenotbeusedforrenalprotection.(Grade1A)Werecommendthatallpatientsrequiringvasopressorshaveanarterialcatheterplacedassoonaspracticalifresourcesareavailable

Slide34Copyright2014SCCM/ESICMVasopressorTherapyWerecomme

InotropicTherapyWerecommendthatatrialofdobutamineinfusionupto20μg/kg/minbeadministeredoraddedtovasopressor(ifinuse)inthepresenceof:myocardialdysfunctionassuggestedbyelevatedcardiacfillingpressuresandlowcardiacoutput,orongoingsignsofhypoperfusion,despiteachievingadequateintravascularvolumeandadequatemeanarterialpressure.

(Grade1C)Werecommendagainsttheuseofastrategytoincreasecardiacindextopredeterminedsupranormallevels.(Grade1B)

Slide35Copyright2014SCCM/ESICMInotropicTherapyWerecommendSSC2012Guidelines

Infection-RelatedIssues

S.OpalScreeningDiagnosisAntimicrobialtherapySourcecontrolSelectivedecontaminationCopyright2014SCCM/ESICMSSC2012Guidelines

InfectionScreeningforSepsisand

PerformanceImprovement

Werecommendroutinescreeningofpotentiallyinfectedseriouslyillpatientsforseveresepsistoincreasetheearlyidentificationofsepsisandallowimplementationofearlysepsistherapy(Grade1C).Performanceimprovementeffortsinseveresepsisshouldbeusedtoimprovepatientoutcomes(Ungraded).Slide37Copyright2014SCCM/ESICMScreeningforSepsisand

PerfDiagnosis

Werecommendobtainingappropriateculturesbeforeantimicrobialtherapyisinitiatedifsuchculturesdonotcausesignificantdelay(>45minutes)inthestartofantimicrobial(s)administration(Grade1C).Tooptimizeidentificationofcausativeorganisms,werecommendobtainingatleasttwosetsofbloodcultures(bothaerobicandanaerobicbottles)beforeantimicrobialtherapy,withatleastonedrawnpercutaneouslyandonedrawnthrougheachvascularaccessdevice,unlessthedevicewasrecently(<48hours)inserted.Bloodculturescanbedrawnatthesametimeiffromadifferentanatomicsite(Grade1C).Slide38Copyright2014SCCM/ESICMDiagnosisWerecommendobtainiDiagnosis

Culturesofothersites(preferablyquantitativewhereappropriate),suchasurine,cerebrospinalfluid,wounds,respiratorysecretions,orotherbodyfluidsthatmaybethesourceofinfection,shouldalsobeobtainedbeforeantimicrobialtherapyifdoingsodoesnotcausesignificantdelayinantibioticadministration(Grade1C).Wesuggesttheuseofthe1,3β-D-glucanassay(Grade2B),mannanandanti-mannanantibodyassays(Grade2C)

wheninvasivecandidiasisisinthedifferentialdiagnosisofinfection.Slide39Copyright2014SCCM/ESICMDiagnosisCulturesofothersiDiagnosis

Werecommendthatimagingstudiesbeperformedpromptlyinattemptstoconfirmapotentialsourceofinfection.Potentialsourcesofinfectionshouldbesampledastheyareidentifiedandinconsiderationofpatientriskfortransportandinvasiveprocedures(eg,carefulcoordinationandaggressivemonitoringifthedecisionismadetotransportforaCT-guidedneedleaspiration).Bedsidestudies,suchasultrasound,mayavoidpatienttransport(Ungraded).Slide40Copyright2014SCCM/ESICMDiagnosisWerecommendthatimAntimicrobialTherapy

Theadministrationofeffectiveintravenousantimicrobialswithinthefirsthourofrecognitionofsepticshock(Grade1B)andseveresepsiswithoutsepticshock(Grade1C)shouldbethegoaloftherapy.Remark:Althoughtheweightoftheevidencesupportspromptadministrationofantibioticsfollowingtherecognitionofseveresepsisandsepticshock,thefeasibilitywithwhichcliniciansmayachievethisidealstatehasnotbeenscientificallyevaluated.Slide41Copyright2014SCCM/ESICMAntimicrobialTherapyTheadmiSummary:EarlyAntibioticsforSepsis/SepticShockStudiesStudy/yrDesign

(no.)Population/OutcomeLimitationOtherOutcomeEarlyvs.LateQualityofEvidenceKumar2006(1)Multicentern=2154Septicshockonly;survival-HDRetrospectiveTime-responserelationshipORfordeath:1.119/hdelay,P<.0001Moderate-highforshockBarochia2010(2)Meta-analysisn=654s/ss/SS;survival28daysorHDObservationalbefore-aftern=4studies,homogeneous,I2=0%OR0.58(0.33-0.85),P<.0001ModerateFerrer2009(3)Multicenter(n=2796)ss/SS;survival-HDObservationalbefore-afterTime-responserelationshipOR0.67<1h,P<.01OR0.801-3h,nsOR0.873-6h,nsModerateBarie2005(4)Singlecenter(n=331)SurgicalICUs/ss;survival-HDInceptioncohortTime-responserelationshipOR

1.1021(1.003-1.038)/30min,P<.05LowLevy2010(5)Multicenter(n=15,022)ss/SS;survival-HDObservationalbefore-after<1hfromhospitalward,or<3hfromEDOR0.86(0.79-0.93),P<.0001ModerateElSolh2008(6)Singlecenter(n=174)Age>65yr.Septicshock;survival-28daysObservationalmatchedcase-control<4hfromshockonset;indirect-withotherinterventionsHR

0.54(0.33-0.86),P=.01LowGurnani2010(7)Singlecenter(n=118)Septicshock;survival-28daysObservationalbefore-after<4.5hfromshockonsetOR

0.46(0.19-0.84),P<.01byMVRLowNguyen2007(8)Singlecenter(n=330)ss/SS;survival-HDObservationalbefore-after<4hfromonsetOR

0.38(0.18-0.80),P<.05byMVRLowCastellanos-Ortega2010(9)Singlecenter(n=480)Septicshock;survival-HDObservationalbefore-after<1hfromhospitalward,or<3hfromEDOR

0.68(0.43-1.09),P=.109(ns)byMVRLowGaienski2010(10)Singlecenter(n=261)ss/SS;survival-HDObservationalcohortstudyEDtimetoeffectiveantibioticORfordeath1.135/hdelay,P<.05LowLarsen2011(11)Singlecenter(n=345)Pediatricsepticshock-HDObservationalbefore-afterPediatricEDtimetofullbundle,<3hantibioticMortalityreduction8.4to3.5%(P=.07)LowDellingerRP.CritCareMed2013;41:580-637Slide42Copyright2014SCCM/ESICMSummary:EarlyAntibioticsforAntimicrobialTherapy

Werecommendthatinitialempiricanti-infectivetherapyincludeoneormoredrugsthathaveactivityagainstalllikelypathogens(bacterialand/orfungalorviral)andthatpenetrateinadequateconcentrationsintothetissuespresumedtobethesourceofsepsis

(Grade1B).Theantimicrobialregimenshouldbereassesseddailyforpotentialde-escalationtopreventthedevelopmentofresistance,toreducetoxicity,andtoreducecosts(Grade1B).Slide43Copyright2014SCCM/ESICMAntimicrobialTherapyWerecomAntimicrobialTherapy

Wesuggesttheuseoflowprocalcitoninlevelsorsimilarbiomarkerstoassisttheclinicianinthediscontinuationofempiricantibioticsinpatientswhoappearedseptic,buthavenosubsequentevidenceofinfection(Grade2C).Slide44Copyright2014SCCM/ESICMAntimicrobialTherapyWesuggeAntimicrobialTherapy

Empirictherapyshouldattempttoprovideantimicrobialactivityagainstthemostlikelypathogensbaseduponeachpatient’spresentingillnessandlocalpatternsofinfection.Wesuggestcombinationempirictherapyforneutropenicpatientswithseveresepsis(Grade2B)andforpatientswithdifficult-to-treat,multidrug-resistantbacterialpathogenssuchasAcinetobacterandPseudomonasspp.(Grade2B).Slide45Copyright2014SCCM/ESICMAntimicrobialTherapyEmpiricEmpiricCombinationvs.MonotherapyforSepticShockAuthor&locationPublStudyNyearResultsOtherLimitationsQualityImportanceKumarManitoba,CanadaCCM2010Retro-spective,propen-sity-matched,multi-center,cohortstudy1223of4662culture+bacterialsepticshock1996-2007Combinationtherapy:↓28-daymortality36.3%vs29.0%,HR0.77,CI0.67-0.88,P=.0002↓ICUmortality35.7%vs28.8%,OR0.75,95%CI0.63-0.92,P=.0006↓Hospitalmortality47.8%vs37.4%,OR0.69,95%CI0.59-0.81,P<0.0001↑Ventilator-freedays10vs17,P=.008↑pressor-freedays23vs25,P=.007AppliedtoGram-positive

andGram-negativeinfectionsRestrictedtopatientstreatedwithβ-lactams+aminogly-cosides,fluoroquin-olonesormacrolides/clindamy-cinMod-erateHighSlide46Copyright2014SCCM/ESICMEmpiricCombinationvs.MonothCombinationvs.MonotherapyforSepsis(continued)Slide47Copyright2014SCCM/ESICMMicek,Kollef;St.Louis,MOAAC2010Retro-spectivecohortStudy,1center760severesepsisorsepticshock+Gram-negativebacteremia2002-2007Combinationtherapy:↓IIAT22.2%vs36.0%,

P<0.001↑Appropriateinitialtherapyifaminoglycosidesareaddedto:Carbapenem:89.4%to94.2%Cefepime:83.4%to89.9%Piperacillin-tazobactam:79.6%to91.4%Predictorsforhospitalmortality:IIAT:AOR2.30,95%CI1.89-2.80↑APACHEII:AOR1.11,95%CI1.09-1.13238(31.3%)IIAT,withhighermortality(51.7%vs36.4%)β-lactams+aminogly-cosidesorfluoro-quinolones

Mod-erateIm-por-tantCombinationvs.MonotherapyfoCombinationvs.MonotherapyforSepsis(continued)Slide48Copyright2014SCCM/ESICMKumarManitobaCanadaCCM2010Meta-analytic/meta-regressionstudy50random-izedorobserva-tionalstudies1980-2007Combinationtherapy:Nooverallmortality/clinicalbenefit,OR0.856(CI95%,0.71-1.03;P=.0943;I2=45’1%)Substantialbenefitinthemostseverelyill:monotherapyriskofdeath>25%,ORofdeath0.51(95%CI0.41-0.64)

ModerateHighGarnachoRello,SpainCCM2007Retro-spectivemulti-centerobserva-tionalcohortstudy183P.aerugin-osaVAP2002-2006Combinationtherapy:↓likelihoodofinappropriatetherapyequaltomonotherapyifappropriateMonotherapy:↑mortality13.6%(95%CI2.6-29.9)Inappropriateempiricaltherapy↑mortality(AHR0.9,95%CI1.07-3.10)

HighImport-antCombinationvs.MonotherapyfoCombinationvs.MonotherapyforSepsis(continued)Al-HasanKentuckyUSAAAC2009Retro-spectivecohortstudy398GNBbactere-miapatients,β-lactamsmonotherapyvs304β-lactams+fluoroqui-nolonecombina-tionCombinationtherapy:↓28-daymortalityamonglessseverelyillpatients4.2%vs8.8%,AHR0.44,95%CI0.20-0.98,P=0.044Equalincriticallyillpatientscomparedwithmonotherapy25.6%vs27.8%,AHR0.87,95%CI0.47-1.62,P=0.660

Lesscriticallyill,differentthanotherpapersMod-erateMod-erateSlide49Copyright2014SCCM/ESICMCombinationvs.MonotherapyfoCombinationvs.MonotherapyforSepsis(continued)DellingerRP.CritCareMed2013;41:580-637Slide50Copyright2014SCCM/ESICMMartínezMensaSpainAAC2010Retro-spective4863GNBbactere-mia678β-lactams+amino-glycosidecombina-tion

Combinationtherapy:Protectivefactorifshock(OR0.6,95%CI0.4-0.9)orneutropenia(OR0.5,95%CI0.3-0.9)ImprovedappropriateempiricaltherapyifESBL,AmpCorP.aeruginosaNooverallassociationwithprognosis

Restrictedtobactere-miaorneutrope-nia+shockHighHighRodríguezRelloCCM2007Prospec-tiveobserva-tionalcohortSecond-aryanalysis529CAPadmittedatICUCombinationtherapy:↑28-in-ICU-survivalifshock(HR1.69