sepsis课件

WarAgainstSepsisCaseBasedSepsisModule BasedonSurvivingSepsisGuidelines2008 CritCareMed2008Vol 36 No 296 327 SurvivingSepsisCampaignGuidelinesforManagementofSevereSepsis SepticShock AnOverview SurvivingSepsiscampaign AGlobalprogramto Reducemortalityratesinseveresepsis A50yroldsmokerpresentstoemergencywithfeverandacuteshortnessofbreathoftwodaysduration Hehasarespiratoryrateof35 minB Pof90 40 pulse120 minregular Spo288 on10Lnasalcannula Heisalertandcommunicating Hehasbroughtachestx raywhichshowsrightlowerzoneopacity Whatdoesthispatienthave Systemicinflammatoryresponsesyndrome SIRS SepsisSeveresepsisSepticshock SIRSANDSEPSIS Sepsisisdefinedasaninfectionplus 2SIRScriteriaTemperature 38 Cor90beats minRespirations 20 minWBCcount 12 000 mm3or10 immatureneutrophils SIRS Severesepsis MODS Septicshock SIRS Severesepsis Sepsis Infection Other Pancreatitis Trauma Burns Sepsis LevyMM etal CritCareMed 2003 31 1250 1256 CritCareMed2008Vol 36 No 296 327 DEFINITIONS SevereSepsisSepsis sepsis inducedorgandysfunctionorTissuehypo perfusion DEFINITIONS Sepsis inducedhypotensionsystolicbloodpressure SBP 40mmHgOr 2SDbelownormalforageintheabsenceofothercausesofhypotension CritCareMed2008Vol 36 No 296 327 DEFINITIONS Septicshocksepsis inducedhypotensionpersistingdespiteadequatefluidresuscitation CritCareMed2008Vol 36 No 296 327 Sepsis inducedtissuehypo perfusion septicshockanelevatedlactateOroliguria DEFINITIONS CritCareMed2008Vol 36 No 296 327 A50yroldsmokerpresentstoemergencywithfeverandacuteshortnessofbreathoftwodaysduration Hehasarespiratoryrateof35 minB Pof90 40 pulse120 minregular Spo288 on10Lnasalcannula Heisalertandcommunicating Hehasbroughtachestx raywhichshowsrightlowerzoneopacity Whatdoesthispatienthave Systemicinflammatoryresponsesyndrome SIRS SepsisSeveresepsisSepticshock Epidemiology SevereSepsis ComparativeIncidenceandMortality Pathophysiology Inflammation Coagulation ImpairedFibrinolysisInSevereSepsis Endothelium AdaptedfromBernardGR etal NEnglJMed 2001 344 699 709 ActivationofCoagulationinSepsis AdaptedfromBernardGR etal NEnglJMed 2001 344 699 709 ActivationofCoagulationinSepsis RoleofEndogenousAPC AdaptedfromBernardGR etal NEnglJMed 2001 344 699 709 SevereSepsisPathophysiology Spronk P Zandstra D Ince C Bench to bedsidereview Sepsisisadiseaseofthemicrocirculation CriticalCare 2004 8 462 468 SepsisisaDiseaseofthe Microcirculation MicrovascularBloodFlowIsImpairedinSevereSepsis Venousblood Arterialblood SO2 0 98 SO20 94 SO2 0 65 SO2 0 86 SO20 65 SO2 0 83 SO2 0 65 Lactate AnIndicatorofTissuePerfusion SerumlactatelevelsareusedtoassessthediseaseseverityandadequacyofglobaltissueperfusionBy productofanaerobicmetabolismiftissuehypoxiaexistsInterpretationofelevatedbloodlactatelevelsinsepsisislimitedbyseveralimportantfactors1 ProductionofeliminationIncreasingglycolysisInhibitionofpyruvatemetabolismGlobalchanges BakkerJ GrisP ConerfilsM etal SerialBloodLactateLevelsCanPredicttheDevelopmentofMultiplePrganFailureFollowingSepticShock AmJSurg1996 171 221 226 IdentifyingAcuteOrganDysfunctionasaMarkerofSevereSepsis Modifiedfromcriteriapublishedin Balk R Pathogenesisandmanagementofmultipleorgandysfunctionorfailureinseveresepsisandsepticshock CritCareClinics 2000 16 2 337 351 andKleinpell R Theroleofthecriticalcarenurseintheassessmentandmanagementofthepatientwithseveresepsis CritCareNursClinNAm 2003 15 27 34 Cardiovascular TachycardiaHypotensionAlteredCVP PAOP Renal OliguriaAnuria Creatinine Hematologic Platelets PT INR aPTT ProteinC D dimer Hepatic Jaundice Liverenzymes Albumin CNS AlteredconsciousnessConfusion Respiratory Tachypnea PaO2 PaO2 FiO2ratio Metabolic MetabolicAcidosis Lactatelevel LactateClearance SevereSepsisPathophysiology Summary Severesepsisisaninflammatory prothrombotic impairedfibrinolyticprocessassociatedwithalterationsinthemicrovasculatureCoagulopathyisprevalentinseveresepsis MANAGEMENTOFSEPSIS A50yroldsmokerpresentstoemergencywithfeverandacuteshortnessofbreathoftwodaysduration Hehasarespiratoryrateof35 minB Pof90 40 pulse120 minregular Spo288 on10Lnasalcannula Heisalertandcommunicating Hehasbroughtachestx raywhichshowsrightlowerzoneopacity Clarifications RecommendationsgroupedbycategoryandnotbyhierarchyGradingofrecommendationimpliesliteraturesupportandnotpriorityofimportance SponsoringOrganizations InfectiousDiseaseSocietyofAmericaInternationalSepsisForumIndianSocietyofCriticalCareMedicineSocietyofCriticalCareMedicineSurgicalInfectionSocietyCanadianCriticalCareSocietyJapaneseSocietyofCriticalCareMedicineJapaneseAssociationofAcuteMedicineGermanSepsisSocietyLatinAmericanSepsisInstitute AmericanAssociationofCritical careNursesAmericanCollegeofChestPhysiciansAmericanCollegeofEmergencyPhysiciansAmericanThoracicSocietyAustralianandNewZealandIntensiveCareSocietyEuropeanSocietyofClinicalMicrobiologyandInfectiousDiseasesEuropeanSocietyofIntensiveCareMedicineEuropeanRespiratorySociety SurvivingSepsisCampaign 2008Update InternationalefforttoincreaseawarenessandimproveoutcomesinseveresepsisEndorsedbyvariousorganizationsincludingSCCM ACCP ACEP SHM AACCN andESICM CritCareMed2008 36 296 327 ModifiedGRADESystem GradingofEvidence1A Strongrecommendation highqualityevidence1B Strongrecommendation moderatequalityofevidence1C Strongrecommendation lowqualityorverylowqualityevidence2A Weakrecommendation highqualityevidence2B Weakrecommendation moderatequalityevidence2C Weakrecommendation lowqualityorverylowqualityofevidence GuyattG etal Chest2006 129 174 81 InitialResuscitation SevereSepsis InitialResuscitation 1st6hours ShouldbeginassoonasthesyndromeisrecognizedandshouldnotbedelayedpendingICUadmission Elevatedserumlactateconcentrationidentifiestissuehypoperfusioninpatientsatriskwhoarenothypotensive ResuscitationGoals Goalsinthefirst6hours CVP 8 12mmHgMAP 65mmHgUrineoutput 0 5ml kg hr Centralvenous SVC ormixedvenousoxygen SvO2 saturation 70 GRADE1C FigureB page948 reproducedwithpermissionfromDellingerRP Cardiovascularmanagementofsepticshock CritCareMed2003 31 946 955 EGDT TreatmentAlgorithm EGDTsubjectsgotmorefluid blood andvasoactivemedsLessoftenventilatedorgivenPACHospitalmortality30 5 vs 46 5 p 0 009 Riversetal NEJM2001 345 1368 TheImportanceofEarlyGoal DirectedTherapyforSepsisInducedHypoperfusion AdaptedfromTable3 page1374 withpermissionfromRiversE NguyenB HavstadS etal Earlygoal directedtherapyinthetreatmentofseveresepsisandsepticshock NEnglJMed2001 345 1368 1377 Whatwasdone SupplementaloxygenstartedIVlineestablished 1literNSgivenInvestigationssentBloodcultures twosetsSputumforgramstainandcultureCompletebloodcountBloodsugar ureacreatinine LFTABGwithlactateandelectrolytesPT PTTXraychest Afterinitialresuscitation Patienthadpulserate 110 mtBP90 60mmHgCentrallinewasputinontherightsideCVPwas8cmH20 Patientwasgiven500mlofnormalsalineover30mtCVPwas12BPwas80 40mmHgNorepinephrinewasstarted8mcg mttomaintainmeanBPof70mmHgHisPCVwas35Scvo2wasfoundtobe65 Dobutaminewasstartedat6mcg kg mtUrineoutputwas 75ml kg hr Case After2hrsPatientBPagaindroppedto70 40mmHgCVP 10cmH2OSodecidedtogivefluidchallengeof500mlnormalsalineover30mts FluidTherapy Fluidresuscitationwitheithernaturalorartificialcolloidsorcrystalloids Grade1BFluidchallengeinpatientswithsuspectedhypovolemiamaystartwith 1000mlofcrystalloidsor300 500mlofcolloidsover30mins Grade1DRateoffluidadministrationshouldbereducedsubstantiallywhencardiacfillingpressures CVPorPAOP increasewithoutconcurrenthemodynamicimprovementGrade1D SSCGuidelines CritCareMed2008 AlbuminandSalineforFluidResuscitationintheICU SAFETrial RCT 7 000pts in16Australian NZICUsExcludedpts aftercardiacsurgery livertransplantandburns4 albuminorNSNosignificantdifference 28 daymortalityNeworganfailure durationofCRRT ormechanicalventilationICUandHospitalLOSGrade1D NEJM2004 350 2247 2256 FluidChallenge4Aspects WhichfluidWhatrateClinicalEndpointStopfluidifreachedPressureend pointStopfluidifreachedSafetylimits FLUIDCHALLENGE WhenToStop WhenToStart FLUIDCHALLENGEHOWTOGIVEIT Baseline 30mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmHO2 10 16 SPO2 97 ChestExam Clear 500mlnormalsalineover30minutes FLUIDCHALLENGE Baseline 30mts AIM Pulsepermin 130 128 110 MeanBPmmHg 50 55 70 CVPCmHO2 10 11 16 SPO2 97 97 ChestExam Clear Clear 500mlnormalsalineover30minutes FLUIDCHALLENGE Baseline 30mts AIM Pulsepermin 130 128 110 MeanBPmmHg 50 55 70 CVPCmHO2 10 11 16 SPO2 97 97 ChestExam Clear Clear 500mlnormalsalineover30minutes Anotherfluidchallenge FLUIDCHALLENGE 500mlnormalsalineover30mint Baseline AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 Safetylimits SpO2creptsatbase FLUIDCHALLENGE 500mlnormalsalineover30minutes Baseline 10mts 30mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear 125 65 11 97 Continue Clear FLUIDCHALLENGE 500mlnormalsalineover30minutes Baseline 10mts 30mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear continue 125 65 11 97 Continue Clear FLUIDCHALLENGE 500mlnormalsalineover30minutes Baseline 10mts 30mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear 125 65 11 97 Continue Clear 115 75 12 97 Clear FLUIDCHALLENGE 500mlnormalsalineover30minutes Baseline 10mts 30mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear STOP 125 65 11 97 Continue Clear 115 75 12 97 Clear FLUIDCHALLENGE 500mlNormalsalineover30minutes Baseline 10mts Pulsepermin 130 128 MeanBPmmHg 50 60 CVPcmH2O 10 12 Chest Clear Clear AIM 110 70 16 FLUIDCHALLENGE 500mlNornalsalineover30minutes Baseline 10mts 20mts Pulsepermin 130 128 120 MeanBPmmHg 50 60 62 CVPcmH2O 10 12 16 Chest Clear Clear Clear AIM 110 70 16 FLUIDCHALLENGE 500mlNornalsalineover30minutes Baseline 10mts 20mts Pulsepermin 130 128 120 MeanBPmmHg 50 60 62 CVPcmH2O 10 12 16 Chest Clear Clear Clear AIM 110 70 16 STOP FLUIDCHALLENGE Baseline 10mts 20mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear 500mlnormalsalineover30minutes 130 50 11 97 Clear FLUIDCHALLENGE Baseline 10mts 20mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear 500mlnormalsalineover30minutes 130 50 11 97 Clear 128 55 11 86 Creptsatbases FLUIDCHALLENGE Baseline 10mts 20mts AIM Pulsepermin 130 110 MeanBPmmHg 50 70 CVPCmH2O 10 16 SPO2 97 Chest Clear Clear STOP 500mlnormalsalineover30minutes 130 50 11 97 Clear 128 55 11 86 Creptsatbases FLUIDCHALLENGE FLUIDCHALLENGE NoFluidChallenge Diagnosis AppropriateculturesMinimum2bloodcultures1percutaneous1fromeachvascularaccess 48hrsGradeD SevereSepsis PrimarySource Pulmonary 50 Abdomen Pelvis 25 Primarybacteremia 15 Urosepsis 10 Skin 5 Vascular 5 Other 15 MartinGS etal NEJM2003 348 1546 MicrobiologyofSepsis MartinGS etal NEJM2003 348 1546 AntibioticTherapy Beginintravenousantibioticswithinfirsthourofrecognitionofseveresepsis GradeE Durationofhypotensionbeforeinitiationofeffectiveantimicrobialtherapyisthecriticaldeterminantofsurvival KumarA etal CritCareMed2006 34 1589 Grade1B AntibioticTherapy Oneormoredrugsactiveagainstlikelybacterialorfungalpathogens Considermicroorganismsusceptibilitypatternsinthecommunityandhospital GradeD AntibioticTherapy Reassessantimicrobialregimenat48 72hrsMicrobiologicandclinicaldataNarrow spectrumantibioticsNon infectiouscauseidentifiedPreventresistance reducetoxicity reducecostsGradeE SourceControl Evaluatepatientforafocusedinfectionamendabletosourcecontrolmeasuresincludingabscessdrainageortissuedebridement MoverapidlyConsiderphysiologicupsetofmeasureIntravascularaccessdevicesGradeE SourceControl Grade1C Vasopressors Eithernorepinephrineordopamineadministeredthroughacentralcatheteristheinitialvasopressororchoice FailureoffluidresuscitationDuringfluidresuscitationGradeD EffectsofDopamine Norepinephrine andEpinephrineontheSplanchnicCirculationinSepticShock Figure2 page1665 reproducedwithpermissionfromDeBackerD CreteurJ SilvaE VincentJL Effectsofdopamine norepinephrine andepinephrineonthesplanchniccirculationinsepticshock Whichisbest CritCareMed2003 31 1659 1667 Vasopressors Donotuselow dosedopamineforrenalprotection GradeB BellomoR etal Lancet2000 356 2139 2143 Vasopressors Inpatientsrequiringvasopressors placeanarterialcatheterassoonaspossible GradeE CirculatingVasopressinLevelsinSepticShock Figure2 page1755reproducedwithpermissionfromSharsharT BlanchardA PaillardM etal Circulatingvasopressinlevelsinsepticshock CritCareMed2003 31 1752 1758 VasopressinandSepticShock VersuscardiogenicshockDecreasesoreliminatesrequirementsoftraditionalpressorsAsapurevasopressorexpectedtodecreasecardiacoutput VasopressorsVasopressin Notareplacementfornorepinephrineordopamineasafirst lineagentConsiderinrefractoryshockdespitehigh doseconventionalvasopressorsIfused administerat0 01 0 04units minuteinadultsGradeE InotropicTherapy Considerdobutamineinpatientswithmeasuredlowcardiacoutputdespitefluidresuscitation Continuetotitratevasopressortomeanarterialpressureof65mmHgorgreater GradeE InotropicTherapy Donotincreasecardiacindextoachieveanarbitrarilypredefinedelevatedlevelofoxygendelivery GradeAYu etal CCM1993 21 830 838Hayes etal NEJM1994 330 1717 1722Gattinoni etal NEJM1995 333 1025 1032 STEROIDS LowDoseSteroidsinSepticShockStudyDesign AnnaneD etal JAMA2000 283 1038 45 LowDoseSteroidsinSepticShock 28DayMortalityAllPatients AnnaneD etal JAMA2000 283 1038 45 CorticusStudy Multicenter double blind RCT52ICUs March2002 Nov2005 3 yrs Pts 18yrswithsepsisandonsetofshockwithintheprevious72h SBP1hour HydrocortisoneorPlacebo 50mgIVq6hx5days50mgIVq12hondays6to850mgIVq24hondays9to11thenstopped SprungC etal NEJM2008 358 111 24 CorticusStudy ACTH250 gstimulationtestNon responder 9 g dLIntendedsamplesize 800500patientsenrolled499analyzable SprungC etal NEJM2008 358 111 24 ACTHStimulationTest SprungC etal NEJM2008 358 111 24 CORTICUS Conclusions HydrocortisoneRXDidnotdecreasemortalityDeceasedtimetoshockreversalWasassoc withanincreasedincidenceof Superinfections includingnewepisodesofsepsisorsepticshockHyperglycemiaHypernatremia SprungC etal NEJM2008 358 111 24 CorticosteroidTherapy IVhydrocortisoneshouldbegivenonlytoadultsepticshockpatientsafterithasbeenconfirmedthattheirBPispoorlyresponsivetofluidresuscitationandvasopressortherapy CritCareMed2008SSCUpdate Grade2C ConsensusStatement ACTHstimtestshouldnotbeusedtoidentifythesubsetofadultpts withsepticshockwhoshouldreceivehydrocortisone 2B Treatmentregimens 100mghydrocortisoneIVq8h100 200mgbolusofhydrocortisonethen10mg h50mghydrocortisoneIVq6hFulldosehydrocortisonetreatmentshouldbecontinuedfor5 7daysbeforetaperingassumingthereisnorecurrenceofsignsofsepsisorshock 2C MarikPE PastoresSM AnnaneD MeduriGU SprungC etal CritCareMed2008 underreview ConsensusStatement Patientswithsepticshockshouldnotreceivedexamethasoneifhydrocortisoneisavailable 2B Fludrocortisoneisoptionalifhydrocortisoneisused 2C Dosesofcorticosteroidscomparableto 300mgofhydrocortisonedailynotbeusedinsepticshock 1A Case Hisbloodsugarwas170mg Bloodurea94mg andcreatinine2 6mg Serumlactate6mmol ltSerumbilirubinwas3mg AST90U ALT87U HisSpo2droppedto82on10litresofoxygenHisABG pH 7 232 PaO2 58 HCO3 15Patientwasput onassistedventilationVolumecontrol TV 6ml kgidealbodyweightRR 20 mtFio2 1PEEP 10Plateaupressurewaskeptbelow30cmH2o Case ThepossibilityofusingActivatedProteincwasdiscussedwiththefamilyanditwasstartedat24mcg kg hraspatienthadfourorganfailureandnocontraindications Drotrecoginalfa activated rhAPC inSevereSepsis ProcoagulantResponseinSepsis RussellJ NEJM2006 PROWESSTrialDrotrecoginalfa activated 24 g kg hrorplacebofor96hours AdministrationofDrotAAinEarlyStageSevereSepsis ADDRESS International randomized placebo controlledstudytoevaluatetheefficacyofDrotAAforadultswithseveresepsisandlowriskofdeathAPACHEII 25orsingle organfailureN 2640patientsTrialterminatedearlybecauseofaprojectedlackofeffect AbrahamE etal NEJM2005 353 1332 41 ADDRESSTrialDrotrecoginalfa activated 24 g kg hrorplacebofor96hours AbrahamE etal NEJM2005 353 1332 1341 RecombinantHumanActivatedProteinC Recommendedinadultptswithsepsis inducedorgandysfunctionassociatedwithahighriskofdeath APACHEII 25 ormultipleorganfailureandwithnocontraindicationsrelatedtobleedingGrade2BAdultpatientswithseveresepsisandlowriskofdeath APACHEII 20 oroneorganfailure especiallysurgicalpts shouldnotreceiveAPCGrade1A SSCGuidelines CritCareMed2008 SeriousBleedingwithrhAPC ClinicalTrials PROWESS 3 5 vs 2 p 0 06 ADDRESS 3 9 vs 2 2 p 0 01 ENHANCE 6 5 RegistrystudiesreporthigherbleedingratesthanRCTsRiskofbleedinginactualpracticemaybehigher MechanicalVentilationofSepsis InducedALI ARDS Mortality ARDSnetMechanicalVentilationProtocolResults Mortality AdaptedfromFigure1 page1306 withpermissionfromTheAcuteRespiratoryDistressSyndromeNetwork NEnglJMed2000 342 1301 1378 MechanicalVentilationofSepsis InducedALI ARDS Reducetidalvolumeover1 2hrsto6ml kgpredictedbodyweightMaintaininspiratoryplateaupressure 30cmH20GradeB MechanicalVentilationofSepsis InducedALI ARDS MinimumPEEPPreventendexpiratorylungcollapseSettingPEEPFIO2requirementThoracopulmonarycomplianceGradeE TheRoleofPronePositioninginARDS 70 ofpronepatientsimprovedoxygenation70 ofresponsewithin1hour10 daymortalityrateinquartilewithlowestPaO2 FIO2ratio 88 Prone 23 1 Supine 47 2 GattinoniL etal NEnglJMed2001 345 568 73 SlutskyAS NEnglJMed2001 345 610 2 TheRoleofPronePositioninginARDS ConsiderpronepositioninginARDSwhen PotentiallyinjuriouslevelsofF1O2orplateaupressureexistNotathighriskfrompositionalchangesGradeE MechanicalVentilationofSevereSepsis Semirecumbentpositionunlesscontraindicatedwithheadofthebedraisedto45oGradeCDrakulovicetal Lancet1999 354 1851 1858 MechanicalVentilationofSepticPatients Useweaningprotocolandaspontaneousbreathingtrial SBT atleastdailyGradeAEly etal NEJM1996 335 1864 1869Esteban etal AJRCCM1997 156 459 465Esteban etal AJRCCM1999 159 512 518 MechanicalVentilationofSepticPatients SBToptionsLowlevelofpressuresupportwithcontinuouspositiveairwaypressure5cmH2OT piece PriortoSBT ArousableHemodynamicallystable withoutvasopressoragents NonewpotentiallyseriousconditionsLowventilatoryandend expiratorypressurerequirementsRequiringlevelsofFIO2thatcouldbesafelydeli