现代急诊医学：脓毒症及脓毒性休克

SepsisandSepticShock

脓毒症及脓毒性休克

Definitions SystemicInflamatoryResponseSyndrome(SIRS): Thesystemicinflammatoryresponsetoavarietyofsevereclinicalinsults(Forexample,infection).

Clinicallyrecognizedbythepresenceof2ormoreofthefollowing:Temperature>38oCor<36oCHeartRate>90bpmRespiratoryRate>20bpmorPaCO2<32mmHgWBC>12,000,<4000or>10%immatureformsDefinitionsSepsis：SIRScriteria

plus

evidenceofinfection,or:WhitecellsinnormallysterilebodyfluidPerforatedviscusRadiographicevidenceofpneumoniaSyndromeassociatedwithahighriskofinfectionDefinitionsSevereSepsis:Sepsisplus>1organdysfunction.MODS.SepticShock: sepsiswithhypotensiondespiteadequatefluidresuscitation,withperfusionabnormalitiesthatcouldinclude,butarenotlimitedto,lacticacidosis,oliguria,and/oracutementalstatus.DefinitionsSevereSepsis: Sepsiscriteria+evidenceoforgandysfunction,including:CV:SystolicBP<90mmHg,MAP<70mmHgforatleast1hourdespitevolumeresuscitation,ortheuseofvasopressors.Renal:Urineoutput<0.5ml/kgbodyweight/hrfor1hourdespitevolumeresuscitationPulmonary:PaO2/FiO2<250ifotherorgandysfunctionpresentor<200ifthelungistheonlydysfunctionalorgan.Hematologic:Plateletcount<80Kordecreasedby50%in3daysMetabolic:pH<7.3andplasmalactate>1.5xuppernormalDefinitionsInfection:microbialphenomenoncharacterisedbyaninflammatoryresponsetothepresenceofmicroorganismsortheinvasionofnormallysterilehosttissuebytheseorganismsBacteraemia:thepresenceofbacteriainthebloodstreamSIRSandSepsisSIRS:SystemicInflammatoryResponseSyndromeFever,leucocytosis,organfailureRecognisesdifficultyofalwaysidentifyinginfection,but…Asaresult,highsensitivitybutlowspecificityNEnglJMed2015;372:1629-38.Of1,171,797patients,atotalof109,663hadinfectionandorganfailure.Amongthese,96,385patients(87.9%)hadSIRS-positiveseveresepsisand13,278(12.1%)hadSIRS-negativeseveresepsis.InfectionParasiteVirusFungusBacteriaTraumaBurnsSepsisSIRSSevereSepsisSevereSIRSshockBSIEpidemiology2002年目标：5年内死亡率降低25%2012年现实：严重脓毒症的病死率30-70%CritCareMed.2014Mar;42(3):625–631“SevereSepsis”istheleadingcauseofdeathin(noncoronary)ICU11thleadingcauseofdeathoverallMorethan750,000casesofseveresepsisinUSannually.IntheUS,morethan500patientsdieofseveresepsisdailyInEuropeanICUs,sepsisandseveresepsisoccurin30%and37%ofthepatientsseveresepsisasthethirdmostcommoncauseofdeathintheUnitedStatesafterheartdiseaseandmalignanttumorsWhyworryaboutsepsis?EpidemiologySepsisconsumessignificanthealthcareresources.Sepsisaccountsfor40%ICUexpendituresInastudyofPatientswhocontractnosocomialinfections,developsepsisandsurvive:ICUstayprolongedanadditional8days.Additionalcostsincurredwere$40,890/patient.sepsisisbecomingmorecommon,especiallyinthehospital,asaresultof:MedicalandtechnologicaladvancesassociatedwithtreatmentsTheincreasingnumberofelderlyordebilitatedpeople,andpatientswithunderlyingdiseasessuchascancer,whorequiretherapyThewidespreaduseofantibiotics,whichencouragesthegrowthofdrug-resistantmicroorganismsEpidemiologyMartinetal:NEnglJMed2003:348:1546USNationalCentreHealthStatistics–June2011Martinetal:NEnglJMed2003:348:1546EpidemiologyMortalitySepsis:30%-50%SepticShock:50%-60%Mortality：1.InferiorAMI5%2.TraumaISS16-247%3.GIH+lowBP11%4.SepticShock25%5.SevereDKA<1%Epidemiology†NationalCenterforHealthStatistics,2001.§AmericanCancerSociety,2001.*AmericanHeartAssociation.2000.‡AngusDCetal.CritCareMed.2001.AIDS*ColonCHF†SevereSepsis‡Cases/100,000

AIDS*SevereSepsis‡AMI†BreastCancer§1838732203002210002190004120013426BreastCancer§Forthoseunderage65,13%ofthosehospitalizedforsepticemiaorsepsisdiedinthehospital,comparedwith1%ofthosehospitalizedforotherconditions.Forthoseaged65andover,20%ofsepticemiaorsepsishospitalizationsendedindeathcomparedwith3%forotherhospitalizations.Only2%ofhospitalizationsin2008wereforsepticemiaorsepsis,yettheymadeup17%ofin-hospitaldeathsPatientshospitalizedforsepticemiaorsepsisweremorethaneighttimesaslikelytodieduringtheirhospitalizationTable.Hospitalizationsforsepticemiaorsepsiscomparedwithhospitalizationsforotherdiagnoses,bydischargedisposition,20081Differenceisstatisticallysignificantatthe0.05level.SOURCE:CDC/NCHS,NationalHospitalDischargeSurvey,2008.CharacteristicSepticemiaorsepsisOtherdiagnosesDispositionPercentRoutine13979Transfertoothershort-termfacility1

6

3Transfertolong-termcareinstitution13010Diedduringthehospitalization117

2Otherornotstated

8

6Total100100

Only2% ofhospitalizations in2008wereforsepticemiaorsepsis,yettheymadeup17%ofin-hospital deathsTotalnationwideinpatientannualcostsoftreatingthoseHospitalizedforsepticemiahavebeenrisingandwereestimatedtobe$14.6billionin2008Mortality•25%mortalityforseveresepsisandsepticshockinAustraliaandNZ•Studiessuggestthatmortalitymaybedecreasingwithtimebutisstillunacceptablyhigh•215000deathsannuallyintheUSA•DelayedrecognitionanddelayedappropriateinitialtreatmentincreasemortalityPeakeS,fortheARISEInvestigators:TheoutcomeofsepsisandsepticshockpresentingtotheEmergencyDepartmentinAustraliaandNewZealand.CriticalCare2007,11(Suppl2):P73sepsisismostlikelytodevelopinpeoplewho:Areveryyoung(eg,prematurebabies)orveryoldHaveaweakened("compromised")immunesystem,oftenbecauseoftreatmentssuchaschemotherapyforcancer,steroids(eg,cortisone)forinflammatoryconditions,etc.Havewoundsorinjuries,suchasthosefromburns,acarcrash,orabulletHavecertainaddictivehabits,suchasalcoholordrugsArereceivingcertaintreatmentsorexaminations(eg,intravenouscatheters,wounddrainage,urinarycathetersAremorepronetodevelopsepsisthanothersbecauseofgeneticfactors(ortheir"genes")WHOISATRISK?EpidemiologyPatientswhoareadmittedtothehospitalwithseriousdiseasesareatthehighestriskofdevelopingsepsisbecauseof:TheirunderlyingdiseaseTheirprevioususeofantibioticsThepresenceofdrug-resistantbacteriainthehospitalThefactthattheyoftenrequireanintravenoustube,urinarycatheter,orwounddrainageEpidemiologyWHOISATRISK?Hospital-acquiredinfectionsaregenerallymoredifficulttomanagethanthoseacquiredinthecommunity,because:TheinfectingmicroorganismismoredangeroustothepatientThepatientisoftenalreadysickThemicroorganismmayberesistanttocommontreatmentsduetothewidespreaduseofantibioticsinhospitalsEpidemiologyWHOISATRISK?Hospitalizationratesforsepsisorsepticemiaweresimilarformalesandfemalesandincreasedwithage.EpidemiologySeveresepsisincidenceandmortalityincreasewithageAngusCritCareMed29:1301,2001MortalityIncidenceQ:WhydoSepticPatientsDie?

A:

OrganFailure

EpidemiologyOrgandysfunctionattimeofseveresepsisrecognitionBernardNEJM344:699,2001RelationshipbetweenmortalityonICUand

thenumberoffailedorgansFromBrealey&Singer,2000Where’stheinfection?Epidemiology•Respiratory35%•Urinarytract35%•IntraAbdominal10%•Unknown10%•Meningitis/septicarthritis/skin/vascularaccessdevices10%Where’stheinfection?EpidemiologyWhat’stheinfection?EpidemiologyPathophysiologyHotchkissetal,NEJM2003348:138ImmuneactivationandimmunosuppressioninsepsisPathophysiology•Pathogenicfeaturesofthemicroorganism•Patient’simmuneresponsetothesefeatures•Failureoftheimmunesystemtocontrolaninitiallylocalisedinfection•Exaggeratedimmuneandinflammatoryresponse•Cellulardysfunction•VasodilationandleakycapillariesPathophysiologyInfectionInflammatoryMediatorsEndothelialDysfunctionVasodilationHypotensionVasoconstrictionEdemaMaldistributionofMicrovascularBloodFlowOrganDysfunctionMicrovascularPluggingIschemiaCellDeathBacterialinfectionExcessivehostresponseHostfactorsleadtocellulardamageOrgandamageDeathPathophysiologyCohen,Nature:2002420:885Management•TRAUMAGoldenHour•AMITimeisMuscle•STROKETimeisBrain•SEPSISTimeisLifeManagementDelayedrecognitionDelayedappropriateinitialtreatmentincreasemortalityManagementHowlikelyisitthatthediagnosisofsepsisisbeingmissed?Isit...ExtremelylikelyVerylikelySomewhatlikelyNotverylikelyNotlikelyatallNotsureTotal(n=497)IntensiveCarePhysicians(n=237)Ramsay,CritCare20048:R409.SepsisProject,Sepsispathway,Sepsistoolkit………….Goals：Reducepreventableharmtopatientswithsepsis:Recognise•Flaggingofsepsisriskfactors,signsandsymptomsatTriage•EarlyinvolvementofseniorcliniciansindiagnosisandManagementResuscitate•Appropriatefluidresuscitation•Promptadministrationofantibiotics-firstintravenousantibioticadministeredwithinonehourofrecognitionManagementScreeningforSepsisandPerformanceImprovementRoutinescreeningofpotentiallyinfectedseriouslyillpatientsforseveresepsistoallowearlierimplementationoftherapy(grade1C).Hospital–basedperformanceimprovementeffortsinseveresepsis(UG).InitialResuscitationMANAGEMENTOFSEVERESEPSIS

Werecommendtheprotocolizedresuscitationofapatientwithsepsisinducedshock,definedastissuehypoperfusion(hypotensionpersistingafterinitialfluidchallengeorbloodlactateconcentration≥4mmol/L).ThisprotocolshouldbeinitiatedassoonashypoperfusionisrecognizedandshouldnotbedelayedpendingICUadmission.MANAGEMENTOFSEVERESEPSISInitialResuscitationCentralvenouspressure:8–12mmHgMeanarterialpressure:≥65mmHgUrineoutput≥0.5mL/kg/hCentralvenous(superiorvenacava)ormixedvenousoxygensaturation≥70%or≥65%,respectivelyDuringthefirst6hrsofresuscitation,thegoalsofinitialresuscitationofsepsis-inducedhypoperfusionshouldincludeallofthefollowingasonepartofatreatmentprotocol(grade1C):MANAGEMENTOFSEVERESEPSISInitialResuscitationWesuggestthatduringthefirst6hrsofresuscitationofseveresepsisorsepticshock,ifScvO2orSVO2of70%or65%,respectively,isnotachievedwithfluidresuscitationtothecentralvenouspressuretarget,thentransfusionofpackedredbloodcellstoachieveahematocritof≥30%and/oradministrationofadobutamineinfusion(uptoamaximumof20μg·kg-1·min-1)beusedtoachievethisgoal(grade2C).InpatientswithelevatedlactatelevelsasamarkeroftissueHypoperfusion,wesuggesttargetingresuscitationtonormalizelactateasrapidlyaspossible(grade2C).MANAGEMENTOFSEVERESEPSISInitialResuscitationInitial

Resuscitation

Bundle“Early-Goal

Directed

Therapy”Completed

within

3

hours

of

diagnosis

a.Draw

Lactate

b.2

sets

of

Blood

cultures

(best

done

within

45

minutes)

c.Broad

spectrum

antimicrobials

(best

done

within

1

hour)

d.At

least

30

mL/Kg

crystalloid

fluid

challenge

MANAGEMENTOFSEVERESEPSISInitialResuscitationCompletewithin6hoursofdiagnosis

a.VasopressortokeepMAP≥65mmHgifgoalsnotmetbyfluidchallenge,Norepinephrineisfirstchoice

b.Ifpersistenthypotensiondespitefluidresuscitationorinitiallactate≥4mmol/L:

CVP:goal8-12mmHg;12-15mmHgforpatientswithmechanically-ventilationor↑intra-abdominalpressure(duetocardiacfillingimpediment)ScvO2:goal≥70%(or,SvO2≥65%)

c.Re-measurelactate:

goalisnormalizinglactate

d.(Othertargets:UoP≥0.5mL/Kg/hr,normalizinglactateasamarkerforimprovedtissuehypoperfusion)Initial

Resuscitation

Bundle“Early‐Goal

Directed

Therapy”MANAGEMENTOFSEVERESEPSISInitialResuscitationInitial

Resuscitation

Bundle“Early-Goal

Directed

Therapy”Global

prevalence

of

sepsis

presentation:

a.Hypotensionwithlactate≥4mmol/L(16.6%),Hypotensiononly(49.5%),Lactate≥4mmol/L(5.4%)b.Mortalityis46.1%,36.7%,30%,respectively一项涉及314名严重脓毒症患者的多中心试验。患者的28天死亡率降低了17.7%(生存率，75.2%vs.57.5%，p=0.001)MANAGEMENTOFSEVERESEPSISInitialResuscitationRiversE,NguyenB,HavstadS,etal.NEnglJMed2001;345:1368–1377EarlyGoal-DirectedTherapyCollaborativeGroupofZhejiangProvince[inChinese].ZhongguoWeiZhongBingJiJiuYiXue2010;6:331–33449.2%33.3%0102030405060StandardTherapyN=133EGDTN=130P=0.01**KeydifferencewasinsuddenCVcollapse,notMODSEarlyGoal-DirectedTherapyResults:

28DayMortalitySuddenCVCollapseMODS21%vs10%

p=0.0222%vs16%P=0.27NEJM2001;345:1368-77.MortalityIntensiveCareMed(2014)40:1623–1633ProCESS。Arandomizedtrialofprotocol-basedcareforearlysepticshock.NEnglJMed2014;370(18):1683-1693

60天后，EGDT组有92名（21.1%）患者死亡，标准治疗组有81名（18.2%）患者死亡，常规治疗组86名（18.9%）患者死亡，程序化标准治疗组与常规治疗组相比无显著性差异。同样的，程序化EGDT组与程序化标准治疗组也无显著性差异。另外，三组患者的90天死亡率、1年死亡率及器官支持率均无显著性差异。ProCESSProCESS。Arandomizedtrialofprotocol-basedcareforearlysepticshock.NEnglJMed2014;370(18):1683-1693

NEnglJMed2014;371:1496-506.TheARISEInvestigatorsandtheANZICSClinicalTrialsGroupTrialofearly,goal-directedresuscitationforsepticshockNEnglJMed.

2015Apr2;372(14):1301-11.ProMISe2015.04更新“Timeofpresentation”isdefinedasthetimeoftriageintheemergencydepartmentor,ifpresentingfromanothercarevenue,fromtheearliestchartannotationconsistentwithallelementsofseveresepsisorsepticshockascertainedthroughchartreview.

DOCUMENTREASSESSMENTOFVOLUMESTATUSANDTISSUEPERFUSIONWITH:

EITHER:

•Repeatfocusedexam(afterinitialfluidresuscitation)

includingvitalsigns,cardiopulmonary,capillaryrefill,pulse,andskinfindings.

ORTWOOFTHEFOLLOWING:

•MeasureCVP

•MeasureScvO2

•Bedsidecardiovascularultrasound

•Dynamicassessmentoffluidresponsivenesswithpassivelegraiseorfluidchallenge

Ofnote,the6-hourbundlehasbeenupdated;the3-hourSSCbundleisnotaffected.Revised4/2015bytheSSCExecutiveCommitteeDiagnosisMANAGEMENTOFSEVERESEPSISWerecommendobtainingappropriateculturesbeforeantimicrobialtherapyisinitiatedifsuchculturesdonotcausesignificantdelay(>45minutes)inantimicrobialadministration.Tooptimizeidentificationofcausativeorganisms,werecommendatleasttwobloodculturesbeobtainedbeforeantibioticswithatleastonedrawnpercutaneouslyandonedrawnthrougheachvascularaccessdevice,unlessthedevicewasrecently(48hrs)inserted.Get

≥

10mL

per

draw.MANAGEMENTOFSEVERESEPSISDiagnosisCulturesofothersites(preferablyquantitativewhereappropriate),suchasurine,cerebrospinalfluid,wounds,respiratorysecretions,orotherbodyfluidsthatmaybethesourceofinfectionshouldalsobeobtainedbeforeantibiotictherapyifnotassociatedwithsignificantdelayinantibioticadministration(grade1C).

Werecommendthatimagingstudiesbeperformedpromptlyinattemptstoconfirmapotentialsourceofinfection.Samplingofpotentialsourcesofinfectionshouldoccurastheyareidentified;however,somepatientsmaybetoounstabletowarrantcertaininvasiveproceduresortransportoutsideoftheICU.Bedsidestudies,suchasultrasound,areusefulinthesecircumstances(grade1C).MANAGEMENTOFSEVERESEPSISDiagnosisIf

the

blood

culture

drawn

from

the

vascular

access

device

turns

positive

≥

2

hours

before

the

peripheral

blood

culture,

data

supports

that

the

vascular

access

device

is

the

source

of

the

infection.Wesuggesttheuseofthe1,3beta-D-glucanassay(2B),mannanandanti-mannanantibodyassaysfortheearlydiagnosisofinvasivecandidiasis(Grade2C)MANAGEMENTOFSEVERESEPSISDiagnosisAntibioticTherapyMANAGEMENTOFSEVERESEPSISInitial

empiric

broad

spectrum

antimicrobial

therapy

(selected

to

cover

all

suspected

organism)

within

1

hour

after

recognition

of

septic

shock

and

severe

sepsis

without

septic

shock

Mortality

rises

every

hour

without

antimicrobials

MANAGEMENTOFSEVERESEPSISAntibioticTherapyWerecommendthatintravenousantibiotictherapybestartedasearlyaspossibleandwithinthefirsthourofrecognitionofsepticshock(1B)andseveresepsiswithoutsepticshock(1D).Appropriateculturesshouldbeobtainedbeforeinitiatingantibiotictherapybutshouldnotpreventpromptadministrationofantimicrobialtherapy(grade1D).MANAGEMENTOFSEVERESEPSISAntibioticTherapyWerecommendthatinitialempiricalanti-infectivetherapyincludeoneormoredrugsthathaveactivityagainstalllikelypathogens(bacterialand/orfungal)andthatpenetrateinadequateconcentrationsintothepresumedsourceofsepsis(grade1B).Werecommendthattheantimicrobialregimenbereassesseddailytooptimizeactivity,topreventthedevelopmentofresistance,toreducetoxicity,andtoreducecosts(grade1C).MANAGEMENTOFSEVERESEPSISAntibioticTherapyWesuggestcombinationtherapyforpatientswithknownorsuspectedPseudomonasinfectionsasacauseofseveresepsis(grade2D).Wesuggestcombinationempiricaltherapyforneutropenicpatientswithseveresepsis(grade2D).Whenusedempiricallyinpatientswithseveresepsis,wesuggestthatcombinationtherapyshouldnotbeadministeredfor＞3–5days.De-escalationtothemostappropriatesingletherapyshouldbeperformedassoonasthesusceptibilityprofileisknown(grade2D).MANAGEMENTOFSEVERESEPSISAntibioticTherapyWerecommendthatthedurationoftherapytypicallybe7–10days;longercoursesmaybeappropriateinpatientswhohaveaslowclinicalresponse,undrainablefociofinfection,orimmunologicdeficiencies,includingneutropenia(grade1D).Werecommendthatifthepresentingclinicalsyndromeisdeterminedtobeduetoanoninfectiouscause,antimicrobialtherapybestoppedpromptlytominimizethelikelihoodthatthepatientwillbecomeinfectedwithanantibiotic-resistantpathogenorwilldevelopadrug-relatedadverseeffect(grade1D).Usepro-calcitoninlevelorothermarkerstoconsiderdiscontinuationofempiric

antibioticfor

those

whowas

Initiallydiagnosed

septic,but

haveno

subsequentevidenceofinfection.

MANAGEMENTOFSEVERESEPSISAntibioticTherapyCombineempirialtherapy

for

neutopenicpatients,MDR…

Doublecover

P.aeruginosa

withextended-spectrumbeta-lactamsandaminoglycoside

orfluoroquinolone.For

Streppneumo,use

beta-lactamandmacrolide.

WesuggestSODandSDDtoreducetheincidenceofventilator-associatedpneumoniainhealthcaresettingsinregionswherethismethodologyhasbeenfoundtobeeffective(2B)MANAGEMENTOFSEVERESEPSISAntibioticTherapySourceControlMANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISSourceControlAspecificanatomicaldiagnosisofinfectionrequiringconsiderationforemergentsourcecontrolbesoughtanddiagnosedorexcludedasrapidlyaspossible,andinterventionbeundertakenforsourcecontrolwithinthefirst12hrafterthediagnosisismade,iffeasible(grade1C).Wheninfectedperipancreaticnecrosisisidentifiedasapotentialsourceofinfection,definitiveinterventionisbestdelayeduntiladequatedemarcationofviableandnonviabletissueshasoccurred(grade2B).MANAGEMENTOFSEVERESEPSISSourceControlWhensourcecontrolinaseverelysepticpatientisrequired,theeffectiveinterventionassociatedwiththeleastphysiologicinsultshouldbeused(eg,percutaneousratherthansurgicaldrainageofanabscess)(UG).Ifintravascularaccessdevicesareapossiblesourceofseveresepsisorsepticshock,theyshouldberemovedpromptlyafterothervascularaccesshasbeenestablished(UG).FluidTherapyI.MANAGEMENTOFSEVERESEPSISWerecommendcrystalloidsbeusedintheinitialfluidresuscitationinpatients(Grade1A).Wesuggestaddingalbuminintheinitialfluidresuscitationregimenofseveresepsisandsepticshockiftheserumalbuminisknownoranticipatedtobelow(Grade2B).3.Werecommendagainsttheuseofhydroxyethylethylstarcheswithmolecularweight>140kDaandoradegreeofsubstitution>0.4(Grade1B).MANAGEMENTOFSEVERESEPSISFluidTherapyMANAGEMENTOFSEVERESEPSISFluidTherapy4.Werecommendthatinitialfluidchallengeinpatientswithsepsis-inducedtissuehypoperfusionwithsuspicionofhypovolemicbestartedwith≥1000mLofcrystalloids(toachieveaminimumof30ml/kgofcrystalloidsinthefirst4to6hours).Morerapidadministrationandgreateramountsoffluid,maybeneededinsomepatients(Grade1B).5.Werecommendthatafluidchallengetechniqueusingincrementalfluidbolusesbeappliedwhereinfluidadministrationiscontinuedaslongasthehemodynamicimprovementeitherbasedondynamic(e.g.deltapulsepressure,strokevolumevariation…)orstatic(egcardiacoutput,arterialpressure,heartrate)variablescontinues(Grade1C)(Grade1C).VasopressorsMANAGEMENTOFSEVERESEPSIS1.Werecommendthatvasopressortherapyinitialltargetameanarterialpressure(MAP)of65mmHg(grade1C).2.Werecommendnorepinephrineasthefirstchoicevasopressor(administeredthroughacentralcatheterassoonasoneisavailable)(grade1B).MANAGEMENTOFSEVERESEPSISVasopressorsMANAGEMENTOFSEVERESEPSISVasopressors3.Werecommendepinephrine(addedorsubstituted)whenanadditionalagentisneededtomaintainadequatebloodpressure(Grade2B).4.Wesuggestvasopressin0.03units/minutecanbeaddedtoorsubstitutedfornorepinephrine(Grade2)5.Wesuggestdopamineasanalternativevasopressoragenttonorepinephrineinhighlyselectedpatientsatverylowriskofarrhythmiasandwithlowcardiacoutputand/orlowheartrate.(Grade2C).6.Werecommendthatlow-dosedopaminenotbeusedforrenalprotection(grade1A).7.Werecommendthatallpatientsrequiringvasopressorshaveanarterialcatheterplacedassoonaspracticalifresourcesareavailable(grade1B).MANAGEMENTOFSEVERESEPSISVasopressorsMANAGEMENTOFSEVERESEPSISVasopressorsSuperiorvenacavaO2sat

(ScvO2>70%)orMixed

venousoxygensaturation

(SvO2>

65%).Ifcannotachieveby6hours,adddobutamineinfusion

tomax20mcg/Kg/min

orPRBC

transfusion

to

ahematocrit≥30%toMaximizeoxygencarryingcapacity.CVPusage

ismost

readilyavailable,that’s

why

we

use

it.However,it

isconfounded

bypulmonary

HTN,limitation

ofstaticventricularfillingpressuremeasurementassurrogateofresuscitationIfScvO2

isnotavailable,

it’s

ok

touse

lactate-trend-to-normal

asasurrogateofresolution

of

tissuehypoperfusion.

(Non-inferiority

in2

RCT)20%decrease

in

lactateandScvO2≥70%within

first

2hours

ofdiagnosisisassociated

with9.6%

absolutereduction

in

mortality.

InotropicTherapyMANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISInotropicTherapyAtrialofdobutamineinfusionupto20micrograms/kg/minbeadministeredoraddedtovasopressor(ifinuse)inthepresenceof:(a)myocardialdysfunctionassuggestedbyelevatedcardiacfillingpressuresandlowcardiacoutput.(b)ongoingsignsofhypoperfusion,despiteachievingadequateintravascularvolumeandadequateMAP(grade1C).Notusingastrategytoincreasecardiacindextopredeterminedsupranormallevels(grade1B).CorticosteroidsI.MANAGEMENTOFSEVERESEPSISI.MANAGEMENTOFSEVERESEPSISAuthorssuggest

notprovidingintravenouscorticosteroidtherapy

topatientsforwhomfluidresuscitationandvasopressorscanrestoreanadequatebloodpressure.Forthosewithvasopressor-refractorysepticshock,theyrecommendIVhydrocortisoneinacontinuousinfusiontotaling200mg/24hrs—aweakGrade2CWhenhydrocortisoneisgiven,usecontinuousflow(grade2D).I.MANAGEMENTOFSEVERESEPSISNotusingtheACTHstimulationtesttoidentifyadultswithsepticshockwhoshouldreceivehydrocortisone(grade2B).Intreatedpatientshydrocortisonetaperedwhenvasopressorsarenolongerrequired(grade2D).Corticosteroidsnotbeadministeredforthetreatmentofsepsisintheabsenceofshock(grade1D).Wesuggestthatpatientswithsepticshockreceivehydrocortisoneratherthanothersteroids(Grade2B).FurtherwerecommendthathydrocortisonealonebeusedinsteadofhydrocortisoneplusFludrocortisone(Grade1B).RecombinantHumanActivatedProteinC(rhAPC)MANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISBloodProductAdministrationMANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISOncetissuehypoperfusionhasresolvedandintheabsenceofextenuatingcircumstances,suchasmyocardialischemia,severehypoxemia,acutehemorrhage,orischemicheartdisease,werecommendthatredbloodcelltransfusionoccuronlywhenhemoglobinconcentrationdecreasesto<7.0g/dLtotargetahemoglobinconcentrationof7.0–9.0g/dLinadults(grade1B).Notusingerythropoietinasaspecifictreatmentofanemiaassociatedwithseveresepsis(grade1B).Freshfrozenplasmanotbeusedtocorrectlaboratoryclottingabnormalitiesintheabsenceofbleedingorplannedinvasiveprocedures(grade2D).MANAGEMENTOFSEVERESEPSISNotusingantithrombinforthetreatmentofseveresepsisandsepticshock(grade1B).Inpatientswithseveresepsis,administerplateletsprophylacticallywhencountsare<10,000/mm3(10x109/L)intheabsenceofapparentbleeding.Wesuggestprophylacticplatelet