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1、SepsisandSepticShock脓毒症及脓毒性休克DefinitionsSystemicInflamatoryResponseSyndrome(SIRS):Thesystemicinflammatoryresponsetoavarietyofsevereclinicalinsults(Forexample,infection).Clinicallyrecognizedbythepresenceof2ormoreofthefollowing:Temperature38oCor90bpmRespiratoryRate20bpmorPaCO212,000,10%immatureformsDe
2、finitionsSepsis：SIRScriteria plus evidenceofinfection,or:WhitecellsinnormallysterilebodyfluidPerforatedviscusRadiographicevidenceofpneumoniaSyndromeassociatedwithahighriskofinfectionDefinitionsSevereSepsis:Sepsisplus1organdysfunction.MODS.SepticShock:sepsiswithhypotensiondespiteadequatefluidresuscit
3、ation,withperfusionabnormalitiesthatcouldinclude,butarenotlimitedto,lacticacidosis,oliguria,and/oracutementalstatus.DefinitionsSevereSepsis:Sepsis criteria + evidence of organ dysfunction, including:CV:SystolicBP90mmHg,MAP70mmHgforatleast1hourdespitevolumeresuscitation,ortheuseofvasopressors.Renal:U
4、rineoutput0.5ml/kgbodyweight/hrfor1hourdespitevolumeresuscitationPulmonary:PaO2/FiO2250ifotherorgandysfunctionpresentor200ifthelungistheonlydysfunctionalorgan.Hematologic:Plateletcount80Kordecreasedby50%in3daysMetabolic:pH1.5xuppernormalNEnglJMed2015;372:1629-38.Of1,171,797patients,atotalof109,663ha
5、dinfectionandorganfailure.Amongthese,96,385patients(87.9%)hadSIRS-positiveseveresepsisand13,278(12.1%)hadSIRS-negativeseveresepsis.InfectionParasiteParasiteVirusVirusFungusFungusBacteriaBacteriaTraumaTraumaBurnsBurnsSepsisSIRSSevereSevereSepsisSepsisSevereSevereSIRSSIRSshockBSIBSIEpidemiology2002年目标
6、：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):625631“SevereSepsis”istheleadingcauseofdeathin(noncoronary)ICU11thleadingcauseofdeathoverall11thleadingcauseofdeathoverallMorethan750,000casesofseveresepsisinUSannually.Morethan750,000casesofseveresepsisinUSannually.IntheUS,morethan500pati
7、entsdieofseveresepsisdailyInEuropeanICUs,sepsisandseveresepsisoccurin30%and37%ofthepatientsseveresepsisasthethirdmostcommoncauseofdeathintheUnitedStatesafterheartdiseaseandmalignanttumorsWhyworryaboutsepsis?Epidemiology Sepsisconsumessignificanthealthcareresources.Sepsisconsumessignificanthealthcare
8、resources. Sepsisaccountsfor40%ICUexpendituresSepsisaccountsfor40%ICUexpenditures InastudyofPatientswhocontractnosocomialinfections,InastudyofPatientswhocontractnosocomialinfections,developsepsisandsurvive:developsepsisandsurvive: ICUstayprolongedanadditional8days.ICUstayprolongedanadditional8days.
9、Additionalcostsincurredwere$40,890/patient.Additionalcostsincurredwere$40,890/patient.sepsisisbecomingmorecommon,especiallyinthehospital,asaresultof:MedicalandtechnologicaladvancesassociatedwithtreatmentsTheincreasingnumberofelderlyordebilitatedpeople,andpatientswithunderlyingdiseasessuchascancer,wh
10、orequiretherapyThewidespreaduseofantibiotics,whichencouragesthegrowthofdrug-resistantmicroorganismsEpidemiologyUSNationalCentreHealthStatisticsJune2011EpidemiologyMortalitySepsis: 30% - 50%Septic Shock: 50% - 60%Mortality：1.InferiorAMI5%2.TraumaISS16-247%3.GIH+lowBP11%4.SepticShock25%5.SevereDKA45mi
11、nutes)inantimicrobialadministration.Tooptimizeidentificationofcausativeorganisms,werecommendatleasttwobloodculturesbeobtainedbeforeantibioticswithatleastonedrawnpercutaneouslyandonedrawnthrougheachvascularaccessdevice,unlessthedevicewasrecently(48hrs)inserted.Get10mLperdraw.MANAGEMENTOFSEVERESEPSISD
12、iagnosisCulturesofothersites(preferablyquantitativewhereappropriate),suchasurine,cerebrospinalfluid,wounds,respiratorysecretions,orotherbodyfluidsthatmaybethesourceofinfectionshouldalsobeobtainedbeforeantibiotictherapyifnotassociatedwithsignificantdelayinantibioticadministration(grade1C).Werecommend
13、thatimagingstudiesbeperformedpromptlyinattemptstoconfirmapotentialsourceofinfection.Samplingofpotentialsourcesofinfectionshouldoccurastheyareidentified;however,somepatientsmaybetoounstabletowarrantcertaininvasiveproceduresortransportoutsideoftheICU.Bedsidestudies,suchasultrasound,areusefulinthesecir
14、cumstances(grade1C).MANAGEMENTOFSEVERESEPSISDiagnosisIfthebloodculturedrawnfromthevascularaccessdeviceturnspositive2hoursbeforetheperipheralbloodculture,datasupportsthatthevascularaccessdeviceisthesourceoftheinfection.Wesuggesttheuseofthe1,3beta-D-glucanassay(2B),mannanandanti-mannanantibodyassaysfo
15、rtheearlydiagnosisofinvasivecandidiasis(Grade2C)MANAGEMENTOFSEVERESEPSISDiagnosisAntibioticTherapyMANAGEMENTOFSEVERESEPSISInitialempiricbroadspectrumantimicrobialtherapy(selectedtocoverallsuspectedorganism)within1hourafterrecognitionofsepticshockandseveresepsiswithoutsepticshockMortalityriseseveryho
16、urwithoutantimicrobialsMANAGEMENTOFSEVERESEPSISAntibioticTherapyWerecommendthatintravenousantibiotictherapybestartedasearlyaspossibleandwithinthefirsthourofrecognitionofsepticshock(1B)andseveresepsiswithoutsepticshock(1D).Appropriateculturesshouldbeobtainedbeforeinitiatingantibiotictherapybutshouldn
17、otpreventpromptadministrationofantimicrobialtherapy(grade1D).MANAGEMENTOFSEVERESEPSISAntibioticTherapyWerecommendthatinitialempiricalanti-infectivetherapyincludeoneormoredrugsthathaveactivityagainstalllikelypathogens(bacterialand/orfungal)andthatpenetrateinadequateconcentrationsintothepresumedsource
18、ofsepsis(grade1B).Werecommendthattheantimicrobialregimenbereassesseddailytooptimizeactivity,topreventthedevelopmentofresistance,toreducetoxicity,andtoreducecosts(grade1C).MANAGEMENTOFSEVERESEPSISAntibioticTherapyWesuggestcombinationtherapyforpatientswithknownorsuspectedPseudomonasinfectionsasacauseo
19、fseveresepsis(grade2D).Wesuggestcombinationempiricaltherapyforneutropenicpatientswithseveresepsis(grade2D).Whenusedempiricallyinpatientswithseveresepsis,wesuggestthatcombinationtherapyshouldnotbeadministeredfor35days.De-escalationtothemostappropriatesingletherapyshouldbeperformedassoonasthesusceptib
20、ilityprofileisknown(grade2D).MANAGEMENTOFSEVERESEPSISAntibioticTherapyWerecommendthatthedurationoftherapytypicallybe710days;longercoursesmaybeappropriateinpatientswhohaveaslowclinicalresponse,undrainablefociofinfection,orimmunologicdeficiencies,includingneutropenia(grade1D).Werecommendthatiftheprese
21、ntingclinicalsyndromeisdeterminedtobeduetoanoninfectiouscause,antimicrobialtherapybestoppedpromptlytominimizethelikelihoodthatthepatientwillbecomeinfectedwithanantibiotic-resistantpathogenorwilldevelopadrug-relatedadverseeffect(grade1D).Usepro-calcitoninlevelorothermarkerstoconsiderdiscontinuationof
22、empiricantibioticforthosewhowasInitiallydiagnosedseptic,buthavenosubsequentevidenceofinfection.MANAGEMENTOFSEVERESEPSISAntibioticTherapyCombineempirialtherapyforneutopenicpatients,MDRDoublecoverP.aeruginosawithextended-spectrumbeta-lactamsandaminoglycosideorfluoroquinolone.ForStreppneumo,usebeta-lac
23、tamandmacrolide.WesuggestSODandSDDtoreducetheincidenceofventilator-associatedpneumoniainhealthcaresettingsinregionswherethismethodologyhasbeenfoundtobeeffective(2B)MANAGEMENTOFSEVERESEPSISAntibioticTherapySourceControlMANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISSourceControlAspecificanatomicaldi
24、agnosisofinfectionrequiringconsiderationforemergentsourcecontrolbesoughtanddiagnosedorexcludedasrapidlyaspossible,andinterventionbeundertakenforsourcecontrolwithinthefirst12hrafterthediagnosisismade,iffeasible(grade1C).Wheninfectedperipancreaticnecrosisisidentifiedasapotentialsourceofinfection,defin
25、itiveinterventionisbestdelayeduntiladequatedemarcationofviableandnonviabletissueshasoccurred(grade2B).MANAGEMENTOFSEVERESEPSISSourceControlWhensourcecontrolinaseverelysepticpatientisrequired,theeffectiveinterventionassociatedwiththeleastphysiologicinsultshouldbeused(eg,percutaneousratherthansurgical
26、drainageofanabscess)(UG).Ifintravascularaccessdevicesareapossiblesourceofseveresepsisorsepticshock,theyshouldberemovedpromptlyafterothervascularaccesshasbeenestablished(UG).FluidTherapyI.MANAGEMENTOFSEVERESEPSIS1.Werecommendcrystalloidsbeusedintheinitialfluidresuscitationinpatients(Grade1A).2.Wesugg
27、estaddingalbuminintheinitialfluidresuscitationregimenofseveresepsisandsepticshockiftheserumalbuminisknownoranticipatedtobelow(Grade2B).3.Werecommendagainsttheuseofhydroxyethylethylstarcheswithmolecularweight140kDaandoradegreeofsubstitution0.4(Grade1B).MANAGEMENTOFSEVERESEPSISFluidTherapyMANAGEMENTOF
28、SEVERESEPSISFluidTherapy4.Werecommendthatinitialfluidchallengeinpatientswithsepsis-inducedtissuehypoperfusionwithsuspicionofhypovolemicbestartedwith1000mLofcrystalloids(toachieveaminimumof30ml/kgofcrystalloidsinthefirst4to6hours).Morerapidadministrationandgreateramountsoffluid,maybeneededinsomepatie
29、nts(Grade1B).5.Werecommendthatafluidchallengetechniqueusingincrementalfluidbolusesbeappliedwhereinfluidadministrationiscontinuedaslongasthehemodynamicimprovementeitherbasedondynamic(e.g.deltapulsepressure,strokevolumevariation)orstatic(egcardiacoutput,arterialpressure,heartrate)variablescontinues(Gr
30、ade1C)(Grade1C).VasopressorsMANAGEMENTOFSEVERESEPSIS1.Werecommendthatvasopressortherapyinitialltargetameanarterialpressure(MAP)of65mmHg(grade1C).2.Werecommendnorepinephrineasthefirstchoicevasopressor(administeredthroughacentralcatheterassoonasoneisavailable)(grade1B).MANAGEMENTOFSEVERESEPSISVasopres
31、sorsMANAGEMENTOFSEVERESEPSISVasopressors3.Werecommendepinephrine(addedorsubstituted)whenanadditionalagentisneededtomaintainadequatebloodpressure(Grade2B).4.Wesuggestvasopressin0.03units/minutecanbeaddedtoorsubstitutedfornorepinephrine(Grade2)5.Wesuggestdopamineasanalternativevasopressoragenttonorepi
32、nephrineinhighlyselectedpatientsatverylowriskofarrhythmiasandwithlowcardiacoutputand/orlowheartrate.(Grade2C).6.Werecommendthatlow-dosedopaminenotbeusedforrenalprotection(grade1A).7.Werecommendthatallpatientsrequiringvasopressorshaveanarterialcatheterplacedassoonaspracticalifresourcesareavailable(gr
33、ade1B).MANAGEMENTOFSEVERESEPSISVasopressorsMANAGEMENTOFSEVERESEPSISVasopressorsSuperiorvenacavaO2sat(ScvO270%)orMixedvenousoxygensaturation(SvO265%).Ifcannotachieveby6hours,adddobutamineinfusiontomax20mcg/Kg/minorPRBCtransfusiontoahematocrit30%toMaximizeoxygencarryingcapacity.CVPusageismostreadilyav
34、ailable,thatswhyweuseit.However,itisconfoundedbypulmonaryHTN,limitationofstaticventricularfillingpressuremeasurementassurrogateofresuscitationIfScvO2isnotavailable,itsoktouselactate-trend-to-normalasasurrogateofresolutionoftissuehypoperfusion.(Non-inferiorityin2RCT)20%decreaseinlactateandScvO270%wit
35、hinfirst2hoursofdiagnosisisassociatedwith9.6%absolutereductioninmortality.InotropicTherapyMANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISInotropicTherapyAtrialofdobutamineinfusionupto20micrograms/kg/minbeadministeredoraddedtovasopressor(ifinuse)inthepresenceof:(a)myocardialdysfunctionassuggestedbye
36、levatedcardiacfillingpressuresandlowcardiacoutput.(b)ongoingsignsofhypoperfusion,despiteachievingadequateintravascularvolumeandadequateMAP(grade1C).Notusingastrategytoincreasecardiacindextopredeterminedsupranormallevels(grade1B).CorticosteroidsI.MANAGEMENTOFSEVERESEPSISI.MANAGEMENTOFSEVERESEPSISAuth
37、orssuggestnotprovidingintravenouscorticosteroidtherapytopatientsforwhomfluidresuscitationandvasopressorscanrestoreanadequatebloodpressure.Forthosewithvasopressor-refractorysepticshock,theyrecommendIVhydrocortisoneinacontinuousinfusiontotaling200mg/24hrsaweakGrade2CWhenhydrocortisoneisgiven,usecontin
38、uousflow(grade2D).I.MANAGEMENTOFSEVERESEPSISNotusingtheACTHstimulationtesttoidentifyadultswithsepticshockwhoshouldreceivehydrocortisone(grade2B).Intreatedpatientshydrocortisonetaperedwhenvasopressorsarenolongerrequired(grade2D).Corticosteroidsnotbeadministeredforthetreatmentofsepsisintheabsenceofsho
39、ck(grade1D).Wesuggestthatpatientswithsepticshockreceivehydrocortisoneratherthanothersteroids(Grade2B).FurtherwerecommendthathydrocortisonealonebeusedinsteadofhydrocortisoneplusFludrocortisone(Grade1B).RecombinantHumanActivatedProteinC(rhAPC)MANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISBloodProduc
40、tAdministrationMANAGEMENTOFSEVERESEPSISMANAGEMENTOFSEVERESEPSISOncetissuehypoperfusionhasresolvedandintheabsenceofextenuatingcircumstances,suchasmyocardialischemia,severehypoxemia,acutehemorrhage,orischemicheartdisease,werecommendthatredbloodcelltransfusionoccuronlywhenhemoglobinconcentrationdecreas
41、esto7.0g/dLtotargetahemoglobinconcentrationof7.09.0g/dLinadults(grade1B).Notusingerythropoietinasaspecifictreatmentofanemiaassociatedwithseveresepsis(grade1B).Freshfrozenplasmanotbeusedtocorrectlaboratoryclottingabnormalitiesintheabsenceofbleedingorplannedinvasiveprocedures(grade2D).MANAGEMENTOFSEVE
42、RESEPSISNotusingantithrombinforthetreatmentofseveresepsisandsepticshock(grade1B).Inpatientswithseveresepsis,administerplateletsprophylacticallywhencountsare10,000/mm3(10x109/L)intheabsenceofapparentbleeding.Wesuggestprophylacticplatelettransfusionwhencountsare20,000/mm3(20x109/L)ifthepatienthasasign
43、ificantriskofbleeding.Higherplateletcounts(50,000/mm350x109/L)areadvisedforactivebleeding,surgery,orinvasiveprocedures(grade2D).Recommendedagainstuseofimmunoglobulins.Needmorestudiesinsepsispatients.SUPPORTIVETHERAPYOFSEVERESEPSISMechanicalVentilationofSepsis-InducedAcuteLungInjury(ALI)/AcuteRespira
44、toryDistressSyndrome(ARDS)SUPPORTIVETHERAPYOFSEVERESEPSISUpdatedBerlinDefinition:ARDS:mild,moderate,severePaO2/FiO2300,200,100.(previouslylabeledALIorARDS)ARDS:targettidalvolumeof6mL/Kgpredictedbodyweight(9%decreaseinallcausemortalitywhenventilatewith6mL/Kgvs12mL/KginARDS);andtargetpassiveinspirator
45、yplateaupressureof30cmH2O.Lowerplateaupressureisassociatedwithlowermortality.ForpatientswithARDSduetoseveresepsis,theauthorsmadeseveralsuggestionsbasedonconsensusopinion/weakevidence:UsinghigherlevelsofPEEP(Grade2C);RecruitmentmaneuversforpatientswithseverehypoxemiawhilereceivinghighPEEPandFiO2(Grad
46、e2C),PronepositioningforpatientswithPaO2/FiO2ratios30cmH2O,itsoktoreducetidalvolumetoaslowas4mL/Kg.Needtomaintainminute-ventilation.Permissivehypercapneawithvolumeassistedorventilationassistedventilationok,aslongastherearenocontraindications,suchasincreasedICP.Bicarbortromethaineinfusionmaybeusefult
47、ofacilitatepermissivehypercapneawithparticularventilatorstrategy.HightidalvolumesandplateaupressuresmaycauseARDS.Nosinglemodeofventilationhasconsistentlyshowadvantageascomparedtoanyothermodeswhenrespectingtheprinciplesoflungprotectiveventilation.UseatleastminimalPEEPtopreventatelectotrauma(failureto
48、keeprecruitedalveoliopen).UsuallyPEEP5cmH2Oisneeded.Minimizingendexpiratoryalveolarcollapsehelpminimizeventilatorinducedlunginjurywhenhighplateaupressuresareinuse.HigherratherthanlowerlevelsofPEEPforsepsis-inducedmoderateorsevereARDS,PaO2/FiO2200mmHghaddecreasedmortalitywithhigherPEEP.SUPPORTIVETHER
49、APYOFSEVERESEPSISRecruitmentmaneuversinsepticpatientswithsevererefractoryhypoxemiaduetoARDS.Pronepositioninginsepsis-inducedARDSpatientwithPaO2/FiO2100mmHg.Othertechniquesarehigh-frequencyoscillatoryventilation,APRV,extracorporealmembraneoxygenation.ConservativefluidstrategyforwithARDSwhodoesnothave
50、tissuehypoperfusion.StudyshowedthattheyusedCVP4mmHgreducedICUstay,butnochangeonmortality.RecommendedagainstbronchodilatorsinpatientwithARDSandnobronchospasm.Rateofdeathbeforedischargeis23%inINHalbuterolgroupvs17.7%inplacebogroup.BALTI-2trial,patientwithIVsalbutamoltreatedpatienthadincreased28daymort
51、ality.Earlyterminationoftrial.HOBelevation30-45degreesinmechanicallyventilatedpatients,decreaseriskofaspirationandVAP.50%ofintubatedpatientinsupinepositiondevelopesVAP,versus9%insemi-recumbentposition.Selectiveoral(chlorhexidine)andGIdecontaminationshouldbeusedtoreduceVAPRecommendedagainstSwan-GanzC
52、atheterSedation,Analgesia,andNeuromuscularBlockadeinSepsisSUPPORTIVETHERAPYOFSEVERESEPSISSUPPORTIVETHERAPYOFSEVERESEPSISContinuousorintermittentsedationbeminimizedinmechanicallyventilatedsepsispatients,targetingspecifictitrationendpoints(grade1B).Neuromuscularblockingagents(NMBAs)beavoidedifpossible
53、inthesepticpatientwithoutARDSduetotheriskofprolongedneuromuscularblockadefollowingdiscontinuation.IfNMBAsmustbemaintained,eitherintermittentbolusasrequiredorcontinuousinfusionwithtrain-of-fourmonitoringofthedepthofblockadeshouldbeused(grade1C).AshortcourseofNMBAofnotgreaterthan48hoursforpatientswith
54、earlysepsis-inducedARDSandaPao2/Fio2180mg/dL.Thisprotocolizedapproachshouldtargetanupperbloodglucose180mg/dLratherthananuppertargetbloodglucose110mg/dL(grade1A).Bloodglucosevaluesbemonitoredevery12hrsuntilglucosevaluesandinsulininfusionratesarestableandthenevery4hrsthereafter(grade1C).Glucoselevelso
55、btainedwithpoint-of-caretestingofcapillarybloodbeinterpretedwithcaution,assuchmeasurementsmaynotaccuratelyestimatearterialbloodorplasmaglucosevalues(UG).RenalReplacementSUPPORTIVETHERAPYOFSEVERESEPSISContinuousrenalreplacementtherapiesandintermittenthemodialysisareequivalentinpatientswithseveresepsi
56、sandacuterenalfailure(grade2B).Usecontinuoustherapiestofacilitatemanagementoffluidbalanceinhemodynamicallyunstablesepticpatients(grade2D).BicarbonateTherapyWerecommendagainsttheuseofsodiumbicarbonatetherapyforthepurposeofimprovinghemodynamicsorreducingvasopressorrequirementsinpatientswithhypoperfusi
57、on-inducedlacticacidemiawithpH7.15(gradeB).II.SUPPORTIVETHERAPYOFSEVERESEPSISDeepVeinThrombosisProphylaxisSUPPORTIVETHERAPYOFSEVERESEPSISPatientswithseveresepsisreceivedailypharmacoprophylaxisagainstvenousthromboembolism(VTE)(grade1B).Thisshouldbeaccomplishedwithdailysubcutaneouslow-molecularweighth
58、eparin(LMWH)(grade1BversustwicedailyUFH,grade2CversusthreetimesdailyUFH).Ifcreatinineclearanceis3daysICUmortalityInhospitalmortalityARR(%)OR(95%CI)Pvalue38.1-31.36.8%52.5-43.09.5%0.69(0.50-0.95)0.020.63(0.46-0.89)0.003OR and p value corrected for type & severity of illnessVan den Berghe et al, N Eng
59、l J Med 2006 354:449研究结果：主要研究终点WuJ,etal.CriticalCare.2013;17(1):R8T1组患者的组患者的28天全因死亡率较对照组降低天全因死亡率较对照组降低9.0%，具有临界，具有临界P值值表4主要结局和预测对照组对照组（n=180)n=180)胸腺肤胸腺肤alal组组（n=181)n=181)P P值值28天死亡率63(35.0%)63(35.0%)47(26.0%)47(26.0%)0.0620.062院内死亡率71(39.4%)71(39.4%)52(28.7%)52(28.7%)0.0320.032ICU内死亡率48(26.7%)48(2
60、6.7%)35(19.3%)35(19.3%)0.0980.098通气时间 中值(IQR)6.0(2.0-14.0)6.0(2.0-14.0)7.0(3.0-13.0)7.0(3.0-13.0)0.7420.742ICU住院时间 中值(IQR)10.5(5.0-20.5)10.5(5.0-20.5)11.0(7.0-20.0)11.0(7.0-20.0)0.2540.254无通气天数* 中值（95%CI）13.0(7.0-18.0)13.0(7.0-18.0)18.0(15.0-21.0)18.0(15.0-21.0)0.0770.077非ICU住院天数* 中值（95%CI）5.0(0.3-1
61、0.7)5.0(0.3-10.7)10.0(6.8-15.0)10.0(6.8-15.0)0.2350.235*：在28天试验期中患者存活且不使用机械通气及ICU的住院天数CI可信区间；IQR：四分位距OtherNewSurvivingSepsisGuidelinesSomeoftheSurvivingSepsiscommitteesotherweakrecommendations/suggestionsincluded:Usingnormalizationoflactatelevelsasanalternategoalinearlygoal-directedtherapyforseveres
62、epsis,ifcentralvenousoxygenationmonitoringisnotavailable(Grade2C).Forpatientsatriskforfungalinfectionasasourceforseveresepsis,checkingoneofthenewerassaysforinvasivecandidiasissuchas1,3-beta-D-glucan,mannan,oranti-mannanELISAantibodytesting(Grade2B/C).Whennoinfectioncanbefoundduringempiricantibiotict
63、herapy,considerusingalowprocalcitoninlevelasasupportivetoolforthedecisiontostopantibiotics(Grade2C). 血浆可溶性髓系细胞触发受体1(solubletrig-geringreceptorexpressedonmyeloidcells，sTREM-1)TREM-1是一个相对分子质量为 30000的糖蛋白，其跨膜信号转导通路在炎症反应级联放大和脓毒症的发生中起着关键作用，感染时在中性粒细胞和单核一巨噬细胞表面表达显著增加，sTREM-1是 TREM-I的可溶形式sTREM-I是诊断细菌感染的可靠指标。
64、研究表明，sTREM-I以 135ng/L为最佳临界值，诊断脓毒症的敏感度为 93.8%，特异度为 84.7%，对脓毒症的早期诊断具有一定价值。一项关于脓毒症患者 28d生存组和死亡组早期血清蛋白表达差异的研究显示，采用双向凝胶电泳、质谱分析检测脓毒症和脓毒性休克患者确诊后 12h内的血液标本发现，生存组补体因子 B、触珠蛋白等血清水平上调，死亡组一 1-B-糖蛋白血清含量更高。 Presepsin（可溶性 CD14亚型，sCD14-ST）是 CD14的 N端片段，往往在细菌感染时产生，是 2004年发现的一种新的生物标志物。 SergeMasson通过从下肢向右心回流300毫升静脉血，PLR相当于一次的液体复苏(CriticalCare2015,19:18)。PLR阳性指标：双腿被动太高4510分钟后，根据医院条件进行下列任何一项检查。达下列指标者为阳性，即病人处于低容量状态，会对输液有效。1）每博输出量增加9%2）脉搏压增加10%3）平均动脉压增加10%4）ETCO2增加5%
