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Sepsisinadults

Updated2017Mar2912:05:00PM:PhenoTestBCKitFDAapprovedtorapidlyidentifyorganismsthatcausebloodstream
infectionsandtoprovideantibioticsensitivityinformationon18selectedantibioticsforsubsetofidentifiedorganisms(FDAPress
Release2017Feb23)viewupdate Showmoreupdates

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RelatedSummaries:
Sepsistreatmentinadults
Sepsisinchildren
Sepsistreatmentinchildren
Lateonsetneonatalsepsis
Glucosecontrolincriticalcare

GeneralInformation

Description:
severeorgandysfunctioncausedbydysregulatedhostresponsetodocumentedorsuspectedinfection(4)
Definitions:
definitionsofsepsischangedconsiderablyin2016withpublicationoftheThirdConsensusDefinitionsforSepsisandSepticShock
(Sepsis3)(4)
2016definitionsarebasedonpredictionsrulefororgandysfunctionandmortality
priordefinitionswerebasedonfulfillmentofsystemicinflammatoryresponsesyndrome(SIRS)
2016consensusdefinitions(Sepsis3):
sepsislifethreateningorgandysfunctioncausedbydysregulatedhostresponsetoinfection(4)
organdysfunctionacutechangeintotalSequentialOrganFailureAssessment(SOFA)score2pointsconsequenttoinfection(4)
assumebaselineSOFAscoreof0inpatientswithoutknownpreexistingorgandysfunction
SOFAscore2pointsassociatedwithoverallmortalityriskofabout10%ingeneralhospitalpopulationwithsuspected
infection
septicshock(4)
sepsiswithunderlyingcirculatoryandcellular/metabolicabnormalitiessevereenoughtosubstantiallyincreasemortality
clinicallydefinedaspersistenthypotensionrequiringvasopressorstomaintainmeanarterialpressure(MAP)65mmHgand
serumlactatelevel2mmol/L(18mg/dL)despiteadequatevolumeresuscitation
associatedwithhospitalmortality40%
quickSOFA(qSOFA)criteria(4)
maybeusedatbesidetoidentifypatientswithsuspectedinfectionlikelytohaveprolongedICUstayortodieinhospital
incorporatesrespiratoryrate22perminute,alteredmentation,andsystolicbloodpressure100mmHg
septicshockdefinitionofhypotensionrequiringvasopressortherapyandserumlactate2mmol/Lafteradequate
fluidresuscitationmayidentifypatientswithsepsisathighestmortalityrisk
basedonsystematicreview,Delphiconsensusreport,andcohortstudies
systematicreviewidentified92sepsisepidemiologystudies
44studiesreportedsepticshockoutcomesin166,479patients
septicshockassociatedcrudemortality46.5%(95%CI42.7%50.3%),resultslimitedbysignificantheterogeneity
Delphiprocesswith19expertsdiscussedsystematicreview,surveys,andbelowcohortstudiestoreachconsensusonvariables
relatedtomortality

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patientsdividedinto6groupsbasedon3identifiedvariables(hypotension[meanarterialpressure<65mmHg]afterfluids,
needforvasopressortherapy,serumlactatelevel)
hypotensionafterfluidsandvasopressortherapywithserumlactatelevels>2mmol/L
hypotensionafterfluidsandvasopressortherapywithserumlactatelevels2mmol/L
hypotensionafterfluidsandnovasopressorsandserumlactatelevels>2mmol/L
serumlactatelevels>2mmol/Landnohypotensionafterfluidsandnovasopressors
serumlactatelevelsbetween24mmol/Landnohypotensionbeforefluidsandnovasopressors
hypotensionafterfluidsandnovasopressorsandserumlactatelevels2mmol/L
variablesevaluatedusingpatientdatafromSurvivingSepsisCampaign(SSC),UniversityofPittsburgMedicalCenter(UPMC),
andKaiserPermanenteNorthernCalifornia(KPNC)
patientswithhypotensionafterfluidsandvasopressortherapywithserumlactatelevels>2mmol/Lhadsignificantlyhigher
mortality(42.3%,95%CI41.2%43.3%)comparedtoothergroupsinriskadjustedcomparisonsinanalysisof18,840
patientsfromtheSSCdatabase
similarresultsinanalysesofUPMCandKPNSdatabases
ReferenceJAMA2016Feb23315(8):775
2003consensusdefinitions:
DynaMedcommentary
2016consensusdefinitionsofsepsisandsepticshock(Sepsis3)havereplacedthe2003consensusdefinitions
updated2016definitionsandclinicalcriteriaclarifytheprior2003descriptionsandfacilitatemoretimelyrecognitionand
managementofpatientswithsepsisandpatientsatriskofsepsis
systemicinflammatoryresponsesyndrome(SIRS)
2of
temperature>38.3degreesC(100.9degreesF)or<36degreesC(96.8degreesF)
heartrate>90beats/minute
respiratoryrate>20breaths/minuteorarterialpartialpressureofcarbondioxide(PaCO2)<32mmHg
whitebloodcellcount(WBC)>12,000/mm3orWBC<4,000/mm3or>10%immatureneutrophils(bands)
aboveabnormalitiesshouldrepresentchangefrombaselinewithoutotherknowncause(suchasleukopeniadueto
chemotherapy)
ReferenceCritCareMed2003Apr31(4):1250
whilecommonlyused,thesedefinitionsareoverlysensitiveandnonspecific,andmaynotcorrelatewellwithoutcomes
(IntensiveCareMed2003Apr29(4):530)
sepsisSIRSduetodocumentedorsuspectedinfection(2,3)
severesepsissepsisplusevidenceofacuteorgandysfunctionortissuehypoperfusion(anyofbelowoccurringduetoinfection)
(1)

sepsisinducedhypotensiondefinedas1of
systolicbloodpressure<90mmHg
meanarterialpressure<70mmHg
systolicbloodpressuredecrease>40mmHg
systolicbloodpressure>2standarddeviationsbelownormalforageinabsenceofothercausesofhypotension
elevatedlacticacid(lactate)level
urineoutput<0.5mL/kg/hourfor>2hoursdespiteadequatefluidresuscitation
acutelunginjurywithpartialpressureofarterialoxygen/fractionofinspiredoxygen(PaO2/FiO2)<250inabsenceofpneumonia
acutelunginjurywithPaO2/FiO2<200inpresenceofpneumonia
creatinine>2mg/dL(176.8mcmol/L)
bilirubin>2mg/dL(34.2mcmol/L)
plateletcount<100,000/mcL
coagulopathy(INR>1.5)
septicshocksepsisinducedhypotensionafteradequatefluidresuscitation(1)
strictadherencetoSIRScriteriamayexcludepatientswithinfection,organfailure,andhighmortalityrate
basedonretrospectivecohortstudy
109,663patientswithinfectionand1organfailurefromtheAustraliaandNewZealandIntensiveCareSociety(ANZICS)
AdultPatientDatabase(APD)from2000to2013wereevaluated
patientdatawasgatheredaspartofroutinequalityassurancebenchmarking
infectionrelateddiagnosesmadeaccordingtoAPACHEIIIatadmission
organfailuredefinedasSequentialOrganFailureAssessment(SOFA)score3
87.9%ofpatientshad2criteriaforSIRS(definedasSIRSpositivesepsis),while12.1%had<2criteriaforSIRS(definedas
SIRSnegativesepsis)
inhospitalmortality
24.5%inpatientswithSIRSpositivesepsis
16.1%inpatientswithSIRSnegativesepsis(p<0.001vs.SIRSpositivesepsis)

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inadjustedanalysis,mortalityincreasedlinearlywitheachadditionalSIRScriteria
oddsratio1.13(95%CI1.111.15)foreachadditionalcriteria
notransitionalincreaseinmortalityriskat2SIRScriteria
ReferenceNEnglJMed2015Apr23372(17):1629
Epidemiology

Incidence/Prevalence:
populationincidenceofseveresepsisabout1caseper1,000,with10%ofintensivecareunitpatientsaffected
basedonreviewof14studiesfrommultiplecountries
ReferenceCritCare2004Aug8(4):222fulltext
UnitedStates
incidenceofsepsisincreasedfrom83to240per100,000populationinUnitedStatesbetween1979and2000
basedonretrospectivecohortstudy
dischargedataonabout750millionhospitalizationsover22yearsevaluated
10,319,418casesofsepsisreported
incidenceofsepsisper100,000populationincreasedfrom82in1979to240in2000
inhospitalmortalitydecreasedfrom27.8%to17.9%
ReferenceNEnglJMed2003Apr17348(16):1546fulltext
sepsismayaccountfor>34%ofinhospitaldeathsinUnitedStates
basedonnationwidecohortof6,555,621hospitalizedadultsinUnitedStatesin2010
4.3%haddiagnosedsepsisand10.9%haddiagnosedorsuspectedsepsis(infectionandacuteorganfailure)
totalinhospitalmortality21.9%
proportionoftotalinhospitalmortalityrelatedtosepsis
34.7%fordiagnosedsepsis
52%fordiagnosedorsuspectedsepsis
consistentresultsinadditionalcohortwith482,828adultshospitalizedinCaliforniain20102012
ReferenceJAMA2014Jul2312(1):90
ageadjustedsepsismortalityinUnitedStatesabout60per100,000persons
basedon20032012CompressedMortalityFiledatainformationon3,108contiguouscountiesintheUnitedStates(excludes
HawaiiandAlaska)
ageadjustedrateofdeathassociatedwithinfection59.6per100,000persons
sepsismortalityhighestinSouthernUnitedStates,particularlyMississippiValley,MiddleGeorgia,andCentralAppalachia
ReferenceCritCareMed2016Jul44(7):1380,commentarycanbefoundinAnnTranslMed2016Aug4(15):295
27%ofadmissionstointensivecareunitsdiagnosedwithseveresepsiswithin24hoursofadmissioninEngland,
Wales,andNorthernIreland
basedoncohortstudyof343,860admissionsto172adultcriticalcareunitsinEngland,Wales,andNorthernIreland19952005
ReferenceCritCare200610(2):R42fulltext
Likelyriskfactors:
immunesystemdeficiencydueto(2)
functionalorsurgicalasplenia
hematologicmalignancy
infectiousdiseases,suchasHIV
immunosuppressingdrugs,suchashighdosecorticosteroidsandmarrowsuppressingchemotherapy
presenceofmalignancyassociatedwithincreasedriskofsepsis
basedonretrospectivecohortstudy
854millionacutecarehospitalizationsand8.9millionpatientswithcancerfrom1979to2001evaluated
1,781,445casesofsepsisoccurredinpatientswithcancer(meanannualincidencerate1,465per100,000cancerpatients)
cancerassociatedwithincreasedriskofsepsis(relativerisk[RR]9.77,95%CI9.679.88)
factorsassociatedwithincreasedriskofsepsisamongpatientswithcancer
AfricanAmericanrace(RR1.28,95%CI1.161.4)
othernonwhiteraces(RR1.47,95%CI1.221.72)
malegender(RR1.17,95%CI1.11.23)
authorsnoteracialandgenderdisparitieslikelyrelatedtosocioeconomicstatusandaccesstocareassimilargapsexistfor
multipleotherchronicmedicalconditions
ReferenceChest2006Jun129(6):1432
Possibleriskfactors:
geneticconditionsconferringsusceptibilitymayinclude(2)
interleukin1b511homozygosity
mannosebindinglectindeficiency
terminalcomplementcomponentdeficiency
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agammaglobulinemia
conditionsassociatedwithdefectsinphagocytosisorleukocytetrafficking
chronicgranulomatousdisease
myeloperoxidasedeficiency
ChediakHigashisyndrome
lazyleukocytesyndrome
leukocyteadhesionmoleculedeficiency
Jobsyndrome(hyperimmunoglobulinE[IgE]syndrome)
EtiologyandPathogenesis

Causes:
infectionwithbacteria,fungus,virus,orparasites (1,2,3)
grampositivebacteriaresponsibleformajorityofsepsiscases,andincidenceofcasescausedbygrampositive
bacteriaandfungalorganismsappearstobeincreasing
basedonretrospectivecohortstudy
dischargedataonabout750millionhospitalizationsover22yearsevaluated
10,319,418casesofsepsisreported
casesofsepsisin2000
grampositivebacteriain52.1%
gramnegativebacteriain37.6%
polymicrobialinfectionin4.7%
anaerobesin1%
fungiin4.6%
between1979and2000
incidenceofgrampositiveinfectionincreasedby26.3%peryear
numberofcasescausedbyfungalorganismsincreasedby20.7%
ReferenceNEnglJMed2003Apr17348(16):1546fulltext
Pathogenesis:
pathogenstimulateshostdefensecells,resultinginsystemicinflammationandactivationofproinflammatorymediators,ultimately
leadingtotissuedamage
primarysourceofinfectionmostcommonlylung,abdomen,orurinarytract
exactpathogenesisunknownfactorsinvolvedmayinclude
surgeofproinflammatorycytokines
delayedapoptosisofneutrophils
declineinlymphocytesduetoapoptosis
dysfunctionofcoagulationandinappropriatedepositionofintravascularfibrin
ReferenceAnnuRevPathol20116:19
proinflammatorymediatorsreportedtobeinvolvedinsepsisinclude(2)
tumornecrosisfactoralpha(TNFalpha)
interleukins
macrophagemigrationinhibitoryfactor(MIF)
solubletriggeringreceptorexpressedonmyeloidcells(sTREM1)
highmobilitygroupboxprotein(HMGB1)
plateletactivatingfactor(PAF)
prostaglandins
leukotrienes
thromboxane
tissuefactor
elevatedcortisolreportedincriticallyillpatientsduetoreducedmetabolicbreakdown(NEnglJMed2013Apr18368(16):1477),
editorialcanbefoundinNEnglJMed2013Apr18368(16):1547
reviewofpathogenesisofvasodilatoryshockcanbefoundinNEnglJMed2001Aug23345(8):588
HistoryandPhysical

History:
Chiefconcern(CC):
symptomshighlyvariableandmayinclude(1,2)
fever
hypothermia
tachypnea
abdominalpainwithvomitingordiarrhea
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lethargy,whichmaybeprofound
alteredmentalstatus
additionalpresentingsymptomsvarywithsourceofinfectionorpresenceofsystemicinflammatoryresponsesyndrome(SIRS)(2)
Physical:
signsofinflammation(1)
fever>38.3degreesC(100.9degreesF)orhypothermiawithcoretemperature<36degreesC(96.8degreesF)
temperatureabnormalities,includingfever,maynotbepresentinallpatients
fever>41.1degreesC(106degreesF)morelikelyresultofnoninfectiouscause
ReferenceLancetInfectDis2002Mar2(3):137
tachycardiawithheartrate>90beats/minuteor>2standarddeviationsabovenormalvalueforage
significantedemaorpositivefluidbalance(>20mL/kgover24hours)
signsofendorganhypoperfusion(1)
hypotension
systolicbloodpressure<90mmHg
meanarterialpressure<70mmHg
systolicbloodpressuredecrease>40mmHginadults
systolicbloodpressure>2standarddeviationsbelownormalvalueforage
tachypnea
withouthypoxiaconsidercompensatoryrespiratoryalkalosisformetabolicacidosis(lacticacidosis)
withhypoxiaconsiderpneumoniawithacutelunginjury/acuterespiratorydistresssyndrome(ALI/ARDS)orpulmonary
edemaorpulmonaryembolism
tachyarrhythmias(suchasatrialfibrillationwithrapidventricularresponse[RVR])cancontributetohypotension
decreasedurineoutput(<0.5mL/kg/hour)
mottlingoftheskinordecreasedcapillaryrefill(>2seconds)
alteredmentalstatus
additionalphysicalfindingsvarywithsourceofsepsis (2)
assessfor
meningismusorabnormalcranialnerveexam
increasedworkofbreathing,basilarcrackles,focalconsolidation,pleuraleffusion,dullnesstopercussion,focallydiminishedair
movement,splinting
regularityofrhythmandpresenceofheartmurmursoradventitialheartsounds,assessvolumestatus,peripheralpulses,and
perfusion
localizedabdominaltenderness,organomegaly,peritonealsigns(suchasreboundorguarding),andascites
rash,petechiae,embolicphenomena(suchasJanewaylesions)
presenceofindwellingcatheters,prostheses,orhardwareandevaluatesites
Diagnosis

Makingthediagnosis:
evaluatepatientsforsymptomsorsignsofsepsisorsepticshock
documentedorsuspectedinfection
someofthefollowing
generalparameters
feverwithcoretemperature>38.3degreesC(100.9degreesF)
hypothermiawithcoretemperature<36degreesC(96.8degreesF)
heartrate>90beats/minuteor>2standarddeviationsabovenormalvalueforage
tachypnea>30breaths/minute
alteredmentalstatus
significantedemaorpositivefluidbalance(>20mL/kgover24hours)
hyperglycemia(plasmaglucose>110mg/dL[7.7mmol/L])inabsenceofdiabetes
inflammatoryparameters
leukocytosiswithwhitebloodcellcount>12,000/mm3
leukopeniawithwhitebloodcellcount<4,000/mm3
normalwhitebloodcellcountwith>10%immatureforms
plasmaCreactiveprotein>2standarddeviationsabovenormalvalue
plasmaprocalcitonin>2standarddeviationsabovenormalvalue
hemodynamicparameters
arterialhypotension
systolicbloodpressure<90mmHg
meanarterialpressure<70mmHg
systolicbloodpressuredecrease>40mmHginadultsor>2standarddeviationsbelownormalvalueforage

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mixedvenousoxygensaturation>70%oncepatienthasbeenfluidrepletedbacktoeuvolemia
cardiacindex>3.5L/minute/m2(exceptinchildrenforwhomvaluesarenormally3.55L/minute/m2)
organdysfunctionparameters
arterialhypoxemia(partialpressureofarterialoxygen/fractionofinspiredoxygen[PaO2/FIO2]<300)
acuteoliguria(urineoutput<0.5mL/kg/houror45mmol/Lforatleast2hours)
creatinineincrease0.5mg/dL(44.2mcmol/L)
coagulationabnormalities(INR>1.5oractivatedpartialthromboplastintime[aPTT]>60seconds)
ileus(absentbowelsounds)
thrombocytopenia(plateletcount<100,000/mm3)
hyperbilirubinemia(totalbilirubin>4mg/dL[70mmol/L])
alteredsensorium/mentalstatus
tissueperfusionparameters
lactatelevel>3mmol/L(3mEq/L)
decreasedcapillaryrefillormottling
ReferenceIntensiveCareMed2003Apr29(4):530
2016consensusdefinitionsofsepsisuseclinicalcriteriatomakediagnosis (4)
sepsislifethreateningorgandysfunctioncausedbydysregulatedhostresponsetoinfection
organdysfunctionacutechangeintotalSequentialOrganFailureAssessment(SOFA)score2pointsconsequentto
infection
assumebaselineSOFAscoreof0inpatientswithoutknownpreexistingorgandysfunction
SOFAscore2pointsassociatedwithoverallmortalityriskofabout10%ingeneralhospitalpopulationwithsuspected
infection
septicshock
sepsiswithunderlyingcirculatoryandcellular/metabolicabnormalitiessevereenoughtosubstantiallyincreasemortality
clinicallydefinedaspersistenthypotensionrequiringvasopressorstomaintainmeanarterialpressure(MAP)65mmHg
andserumlactatelevel2mmol/L(18mg/dL)despiteadequatevolumeresuscitation
associatedwithhospitalmortality40%
quickSOFA(qSOFA)criteria
maybeusedatbesidetoidentifypatientswithsuspectedinfectionlikelytohaveprolongedICUstayordieinhospital
incorporatesrespiratoryrate22perminute,alteredmentation,andsystolicbloodpressure100mmHg
Differentialdiagnosis:
overhalfofallfebrileepisodesinintensivecareunit(ICU)maybeduetononinfectiouscauses(LancetInfectDis2002
Mar2(3):137)
differentialdiagnosisofsystemicinflammatoryresponseincludes (3)
multipletrauma
fullthicknessburn
acutepancreatitis
drugreactions
othercausesofhypotension
hypovolemicshock
cardiogenicshockincludingpericardialtamponade
neurogenicshock
noninfectiousdistributiveshock
adrenocorticalinsufficiency
anaphylacticshock
Testingoverview:
routinebloodtestssuchas
completebloodcountwithdifferential
comprehensivemetabolicpanel(electrolytes,glucose,liverfunctiontests,albumin)
serumlactate
arterialbloodgas(particularlyinpatientswithhypoxia)
bloodcultures(2sets)
ifindwellingline(s)presentandlineinfectionsuspectedobtainperipheralculturesaswellasculturesfromalllines
coagulationstudies
amylaseandlipase
urinalysisandurineculture(onceavailable)
sputumGramstainandcultureinthosewithproductivecough
microbiologiccultures

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SurvivingSepsisCampaignrecommendsperformingroutinecultures(includingbloodcultures)obtainedbeforestarting
antibioticsaslongassamplecollectiondoesnotsubstantiallydelayantibiotics(SCCMBestpracticestatement),including(5)
2setsofbloodcultures(bothaerobicandanaerobicbottles)
1bloodcultureshouldbepercutaneously(orperipherally)drawn
1bloodculturefromeachvascularaccessdeviceinplacefor>48hours
othersitesasclinicallyindicated,suchasurine,cerebrospinalfluid,wounds,respiratorysecretions,andotherbodyfluids
pairedquantitativebloodculturemaybemostaccuratetestfordiagnosisofintravasculardevicerelatedbloodstreaminfection
(level2[midlevel]evidence)
differentialtimetopositivebloodcultures>2hoursbetweensimultaneouscatheterandperipheralbloodculturesmaypredict
catheterrelatedsepsis(level2[midlevel]evidence)
Clinicalpredictionrules:
qSOFAandLODSscoresappeartohavehigherpredictiveperformanceforinhospitalmortalityinpatientsoutsideof
theICUcomparedtoSOFAandSIRScriteria,whileSOFAandLODSscoresappeartohavehighestperformancefor
patientsintheICU(level2[midlevel]evidence)
basedondiagnosticcohortstudy
148,907patientswithsuspectedinfection(89%inintensivecareunits[ICU]s)evaluatedbetween2010and2012at12
hospitalsinUnitedStates
74,453patientsincludedinderivationcohort
74,454patientsincludedinvalidationcohort
overallhospitalmortality4.3%inderivationandvalidationcohorts
quickSequential[Sepsisrelated]OrganFailureAssessment(qSOFA)scorederivedusingfactorssignificantlyassociatedwith
mortalityinderivationcohort(totalscore03points,with1pointeachforsystolichypotension[100mmHg],tachypnea[
22perminute),oralteredmentation)
qSOFAscorecomparedto3otherclinicalcriteria(SequentialOrganFailureAssessment[SOFA],systemicinflammatory
responsesyndrome[SIRS]criteria,andLogisticOrganDysfunctionSystem[LODS])usingvalidationcohort
forpredictinginhospitalmortalityinpatientsintheICU
qSOFAassociatedwithlowerpredictivevalidity(cstatistic0.66)comparedtoSOFA(cstatistic0.74,p<0.001)orLODS(c
statistic0.75,p<0.001)
qSOFAassociatedwithhigherpredictivevalidity(cstatistic0.66)comparedtoSIRScriteria(cstatistic0.64,p=0.01)
SIRSassociatedwithlowerpredictivevaliditycomparedtoSOFAorLODS(p<0.001forboth)
SOFAassociatedwithsimilarpredictivevaliditycomparedtoLODS
forpredictinginhospitalmortalityinpatientsnotintheICU
qSOFAassociatedwithsimilarpredictivevalidity(cstatistic0.81)comparedtoLODS(cstatistic0.81,nosignificant
difference)
qSOFAassociatedwithhigherpredictivevalidity(cstatistic0.81)comparedtoSOFA(cstatisic0.79,p<0.001)orSIRS(c
statistic0.76,p<0.001)
SOFAassociatedwithhigherpredictivevaliditythanSIRS(p<0.001)
qSOFAassociatedwithsimilarperformancein4outsidedatasetswith706,399patientsevaluatedinandoutofhospitals
ReferenceJAMA2016Feb23315(8):762,correctioncanbefoundinJAMA2016May24315(20):2237
qSOFAhassimilarperformanceasSOFAandbetterperformancethanSIRSandseveresepsiscriteriaforpredicting
inhospitalmortalityinpatientswithsuspectedinfectioninemergencydepartment(level2[midlevel]evidence)
basedonvalidationcohortstudy
879adults(medianage67years,53%male)presentingto30emergencydepartmentswithclinicallysuspectedinfectionwere
followeduntilhospitaldischargeordeath
43%hadrespiratorytractinfection
patientswereassessedusingdifferentsepsisdefinitions
25%hadqSOFAscore2
34%hadSOFAscore2
74%had2SIRScriteria
20%fulfilledpreviouscriteriaforseveresepsis(2SIRSelementsplusbloodlactate>2mmol/L)
inhospitalmortality
8%overall
3%inpatientswithqSOFAscore<2
24%inpatientswithqSOFAscore2(p<0.05vs.qSOFAscore<2)
performanceofsepsisdefinitionsforpredictionofinhospitaldeath
Predictor Sensitivity Specificity PPV NPV cstatistic
qSOFA 70% 79% 24% 97% 0.8

SOFA 73% 70% 18% 97% 0.77

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Predictor Sensitivity Specificity PPV NPV cstatistic


SIRScriteria 93% 27% 11% 98% 0.65

Previousseveresepsis 47% 82% 20% 94% 0.65


criteria

Abbreviations:NPV,negativepredictivevaluePPV,positivepredictivevalueqSOFA,quickSequentialOrganFailure
AssessmentSIRS,systemicinflammatoryresponsesyndromeSOFA,SequentialOrganFailureAssessment.
qSOFA>2associatedwithincreasedriskofinhospitalmortalitycomparedtoscore<2(adjustedhazardratio6.2,95%CI
3.810.3)
previouscriteriaforseveresepsisassociatedlowerriskofinhospitalmortality(adjustedHR3.5,95%CI2.25.5),showing
poorerriskstratification
ReferenceJAMA2017Jan17317(3):301,editorialcanbefoundinJAMA2017Jan17317(3):267
SOFAscorehadhigherdiscriminationforinhospitalmortalitythanqSOFAscoreorSIRScriteriainpatientsadmitted
tointensivecarewithinfectionrelateddiagnoses(level1[likelyreliable]evidence)
basedonvalidationcohortstudy
184,875adults(meanage63years,55%male)admittedtoICUwithinfectionrelateddiagnosisfromAustralianandNew
ZealandIntensiveCareSociety(ANZICS)AdultPatientDatabasewereassessed
mostcommondiagnosiswasbacterialpneumonia(17.7%)
18.7%diedinhospitaland55.7%diedinhospitalorhadICUstay3days
baselineSOFAscoreof0wasassumedforallpatients
patientswereassessedusingdifferentsepsisdefinitions
90.1%hadincreaseinSOFAscore2
54.4%hadqSOFAscore2
86.7%had2SIRScriteria
inhospitalmortality
20.2%withSOFAscore2vs.4.4%withSOFAscore<2(p<0.001)
22.8%withqSOFAscore2vs.13.6%withqSOFAscore<2(p<0.001)
19.9%with2SIRScriteriavs.9.8%with<2SIRScriteria(p<0.001)
performanceofsepsisdefinitionsforpredictionofinhospitalmortality
SOFAhadmoderatediscrimination(cstatistic0.75)(p<0.001vs.qSOFAorSIRS)
qSOFAhadmodestdiscrimination(cstatistic0.61)
SIRScriteriahadmodestdiscrimination(cstatistic0.59)
consistentresultsforpredictionofinhospitalmortalityorICUstay3days
ReferenceJAMA2017Jan17317(3):290,editorialcanbefoundinJAMA2017Jan17317(3):267
Bloodtests:
Generalfindings:
bloodtestsroutinelyperformedinclude(1)
completebloodcountwithdifferential
comprehensivemetabolicpanel(electrolytes,glucose,liverfunctiontests,albumin)
serumlactate
arterialbloodgas(particularlyinpatientswithhypoxia)
bloodcultures(2sets)
ifindwellingline(s)presentandlineinfectionsuspectedobtainperipheralculturesaswellasculturesfromalllines
coagulationstudies
amylaseandlipase
urinalysisandurineculture(onceavailable)
sputumGramstainandcultureinthosewithproductivecough
procalcitoninandplasmaCreactiveprotein(CRP)mayalsobeconsidered(5)
generalfindingsmayinclude(1)
evidenceofinflammation
leukocytosiswithwhitebloodcellcount>12,000/mm3
leukopeniawithwhitebloodcellcount<4,000/mm3
normalwhitebloodcellcountwith>10%immatureforms
plasmaCRP>2standarddeviationsabovenormalvalue
plasmaprocalcitonin>2standarddeviationsabovenormalvalue(useofthisassayisinvestigational)
hyperglycemia(plasmaglucose>110mg/dLor7.7mmol/L)intheabsenceofdiabetes
serumlactate>1mmol/L(9mg/dL)
betablockeruseassociatedwithlowerinitialbloodlactatelevelsinpatientswithseveresepsisorsepticshock,
despitesimilardiseaseseverityandmortalityinthesepatients

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basedonretrospectivecohortstudy
260adultswithseveresepsisorsepticshockwereevaluated
25%hadpreviousbetablockertherapy
comparingpatientswithhistoryofbetablockertherapyvs.patientswithouthistoryofbetablockers
initialbloodlactatelevels3.9mmol/Lvs.5.6mmol/Linpatients(p=0.0006,significanceremainedafteradjustingfor
mortality,PredispositionInsultResponseofOrganfailurescore,andsourceofinfection)
meanSequentialOrganFailureAssessment(SOFA)score5vs.5.3(notsignificant)
28daymortality35%vs.49%(p=0.08)
ReferenceCritCareMed2015Dec43(12):2616
organdysfunctionparameters
arterialhypoxemia(partialpressureofarterialoxygen/fractionofinspiredoxygen[PaO2/FIO2]<300)
creatinineincrease0.5mg/dL(44.2mcmol/L)
coagulationabnormalities(INR>1.5oractivatedpartialthromboplastintime[aPTT]>60seconds)
thrombocytopenia(plateletcount<100,000/mm3)
hyperbilirubinemia(totalbilirubin>4mg/dL[70mmol/L])
Bloodcultures:
pairedquantitativebloodculturesmaybemostaccuratemethodofdiagnosingintravasculardevicerelated
bloodstreaminfection(level2[midlevel]evidence)
basedonsystematicreviewlimitedbyheterogeneity
systematicreviewof51studiesassessing8methodsfordiagnosingintravasculardevicerelatedbloodstreaminfection
referencestandardwascathetersegmentcultureorbloodculture
overallsensitivityandspecificityfor8methodsofdiagnosis(significantheterogeneitypresentinallanalysesofsensitivity)
pairedquantitativebloodculturehadsensitivity87%(95%CI83%91%),specificity98%(95%CI97%99%)inanalysisof
10studies
intravasculardevicedrawnquantitativebloodculturehadsensitivity77%(95%CI69%85%),specificity90%(95%CI
88%92%)inanalysisof7studies
quantitativecathetersegmentculturehadsensitivity83%(95%CI78%88%),specificity87%(95%CI85%89%)in
analysisof14studies
acridineorangeleukocytecytospinhadsensitivity72%(95%CI60%84%),specificity91%(95%CI86%96%)inanalysis
of5studies
intravasculardevicedrawnqualitativebloodculturehadsensitivity87%(95%CI80%94%),specificity83%(95%CI
78%88%)inanalysisof7studies
semiquantitativecathetersegmentculturehadsensitivity85%(95%CI81%89%),specificity82%(95%CI80%84%)in
analysisof19studies
differentialtimetopositivityhadsensitivity85%(95%CI78%92%),specificity81%(95%CI75%87%)inanalysisof10
studies
qualitativecathetersegmentculturehadsensitivity72%(95%CI66%78%),specificity90%(95%CI83%97%)inanalysis
of6studies
ReferenceAnnInternMed2005Mar15142(6):451,correctioncanbefoundinAnnInternMed2005May3142(9):803,
commentarycanbefoundinACPJClub2005NovDec143(3):77
differentialtimetopositivebloodcultures>2hoursbetweensimultaneouscatheterandperipheralbloodcultures
maypredictcatheterrelatedsepsis(level2[midlevel]evidence)
basedonretrospectivecohortstudy
64cancerpatientswithsamemicroorganismsculturedfromsimultaneouscentralandperipheralbloodsampleswereevaluated
catheterrelatedsepsisconsideredestablishedin28,ruledoutin14,andindeterminatein22
centralsampletimetopositivity>2hoursearlierthanperipheralsamplepositivityhadsensitivity96.4%andspecificity100%
fordiagnosisofcatheterrelatedsepsis
ReferenceJClinMicrobiol1998Jan36(1):105fulltext
systematicreviewof16diagnosticstudiesevaluatingrapidmolecularandphenotypictechniquesusingpositivebloodculturescan
befoundinClinMicrobiolRev2016Jan29(1):59fulltext
PhenoTestBCKitFDAapprovedtorapidlyidentifyorganismsthatcausebloodstreaminfectionsandtoprovideantibioticsensitivity
informationon18selectedantibioticsforsubsetofidentifiedorganismsFDAPressRelease2017Feb23
Biomarkers:
biomarkers(1,3betaDglucan,galactomannan,procalcitonin)maybeusedtosupportandsupplementclinicalassessment(5)
1,3betaDglucanassay
administrationof>30galbuminwithin2daysof1,3betaDglucanassaymayincreaserateoffalsepositives
(level2[midlevel]evidence)
basedonretrospectivecohortstudywithoutvalidation

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267patients(meanage61.5years)inintensivecareunitatriskfordevelopinginvasivecandidiasiswereassessedusing
serum1,3betaDglucanlevelsandbloodcultures(referencestandard)
receiveroperatingcharacteristiccurvesidentifiedoptimalcutoffvalueof1,3betaDglucan95.9pg/mL,whichhad
sensitivity82.9%
specificity56.7%
administrationof>30gofalbuminwithin2daysof1,3betaDglucanassayassociatedwithincreasedfalsepositiveresults
(p<0.05)
azoleuse,IVimmunoglobulin,andredbloodcellinfusionhadnosignificanteffecton1,3betaDglucanassayresults
ReferenceEurJClinMicrobiolInfectDis2015Feb34(2):357
DynaMedcommentary authorsstatethatfalsepositivesmayoccurduetouseofcellulosefiltersduringalbumin
production.IVimmunoglobulinmayundergosametypeofproductionbutrateoffalsepositivenotshowntobestatistically
significant(p=0.083).
procalcitonin
procalcitoninmayaidindiagnosisofsepsis,butdiagnosticaccuracyoftheassayvarieswidelybetweenstudies
(level2[midlevel]evidence)
basedonsystematicreviewwithheterogeneity
systematicreviewof30studiesevaluatingdiagnosticaccuracyofprocalcitoninforsepsisin3,244patientswithsystemic
inflammatoryresponsesyndrome(SIRS)
overallprevalenceofsepsis57%
20%hadseveresepsis
38%hadsepticshock
inanalysisofall30studies
pooledsensitivity77%(95%CI72%81%)
pooledspecificity79%(95%CI74%84%)
resultslimitedbyheterogeneity
subgroupanalysesevaluatingpatientsaccordingtopopulation,admissioncategory,diseaseseverity,procalcitoninassay,or
referencestandardcouldnotaccountforheterogeneity
ReferenceLancetInfectDis2013May13(5):426
procalcitoninmaynotdifferentiatesepsisfromnoninfectiouscausesofsystemicinflammatoryresponsesyndrome
incriticallyilladults(level2[midlevel]evidence)
basedonsystematicreviewwithpublicationbias
systematicreviewof18studiesofdiagnosticaccuracyofprocalcitoninforsepsiswithwelldefinedreferencestandardsand
microbiologiccultureconfirmationincluding2,097patients
only8studieshaddiagnosisofsepsis/SIRSindependentofresultofprocalcitonintest
prevalenceofsepsisrangedfrom31%to88%
sensitivityofprocalcitoninrangedfrom55%to97%
specificityofprocalcitoninrangedfrom48%to93%
metaanalysisof14phase2studieswith1,602patients
pooledpositivelikelihoodratio3.03(95%CI2.513.65)
poolednegativelikelihoodratio0.43(95%CI0.370.48)
pooleddiagnosticoddsratio7.79(95%CI5.8610.35)
1studyaccountedformostofheterogeneity
metaanalysisof4phase3studieswith495patientsnotpossibleduetohighdegreeofheterogeneity
ReferenceLancetInfectDis2007Mar7(3):210,commentarycanbefoundinLancetInfectDis2007Aug7(8):498
procalcitoninmaybebetterthanCreactiveproteinasdiagnostictestforsepsis(level3[lackingdirect]evidence)
basedonindirectcomparisonsinsystematicreview
systematicreviewof33studiesevaluatingprocalcitoninorCRPlevelsfordiagnosisofinfectioncomplicatedbysystemic
inflammationinadultsincriticalcareoraftersurgeryortrauma
procalcitoninhadglobaloddsratio15.7(95%CI9.127.1)inmetaanalysisof25studieswith2,966patients
CRPhadglobaloddsratio5.4(95%CI3.29.2)inmetaanalysisof15studieswith1,322patients
ReferenceCritCareMed2006Jul34(7):1996,commentarycanbefoundinCritCareMed2007Feb35(2):679
Treatment

Treatmentoverview:
rapiddeliveryofcareandfrequentpatientassessmentarecriticaltoimprovingoutcomesinpatientswithsepsis
immediatemanagement(first1015minutes)
assessforsepticshockinpatientswithsystemicinflammatoryresponsesyndrome(SIRS)
systolicbloodpressure<90mmHg,meanarterialpressure(MAP)<70mmHg
endorganhypoperfusion
alteredmentalstatus

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tachypnea
withouthypoxiaconsidercompensatoryrespiratoryalkalosisformetabolicacidosis(lacticacidosis)
withhypoxiaconsiderpneumoniawithacutelunginjury/acuterespiratorydistresssyndrome(ALI/ARDS)orpulmonary
edemaorpulmonaryembolism
tachycardia
decreasedurineoutput(UOP)(<0.5mL/kg/hour)
slowcapillaryrefill(>2seconds)
performfocusedphysicalexamconcurrentlytoidentifypotentiallocalizingsource
meningismusorcranialnerveabnormalitiesonneurologicexamination
increasedworkofbreathing,basilarcrackles,focalconsolidation,pleuraleffusion,splintingonpulmonaryexamination
regularityandpresenceofmurmursoradventitialheartsounds,volumestatus,peripheralpulses,andperfusionon
cardiovascularexamination
localizedtenderness,organomegaly,peritonealsigns,ascitesonabdominalexamination
rash,petechiae,embolicphenomena,ormottlingofskinonperipheralexamination
presenceofindwellingcatheters,prostheses,orhardware
obtaindiagnostictestingtoidentifyorganhypoperfusionandpotentialsourceofinfectionattimeofexam
bloodtests
completebloodcountwithdifferential,comprehensivemetabolicpanel,amylaseandlipase,lactate,coagulationstudies,
andarterialbloodgas(ABG)ifdevelopinghypoxia
bloodcultures(2sets)beforeantibioticsprovidingthisdoesnotdelaystartsubstantially(SCCMBestpractice
statement)ideallyatleast1peripherallyand1fromanyindwellingcatheter
urinalysisandurineculture
sputumGramstainandcultureifconcernforpneumonia
earlymanagement(initiatewithin1hourofpresentation)
initiateresuscitationandtreatmentimmediately(SCCMBestpracticestatement)
forinitialresuscitationofsepsisinducedhypoperfusion,givecrystalloid(normalsalineorlactatedRingersolution)30
mL/kgwithinfirst3hours(1Lisabout15mL/kgfor70kg[154.3lbs]patient)(SCCMStrongrecommendation,Lowquality
evidence)
considertailoringcrystalloidchoicetoaidincorrectionofelectrolyteimbalancesonceknown
consideralbuminincirrhoticormalnourishedpatientswithhypoalbuminemia
assessfluidresponsivenessatbedsidebasedonphysicalfindings,bloodpressureandheartrate(staticvariables),central
venouspressure(CVP),arterialwaveform,inferiorvenacava(IVC)diametervariation(dynamicvariables)
involumeresponsivepatients,repeatIVfluidbolusesifhypotensionrecursorlactateiselevated
initiatebroadspectrumantibioticsassoonaspossible(SCCMStrongrecommendation,Moderatequalityevidence)
ensureantibioticsaregivenwithin1hourofdevelopmentofhypotension
startingantibioticswithin1hourassociatedwithlowermortalityinpatientswithseveresepsisorsepticshock(level2
[midlevel]evidence)
eachhourofdelayofantimicrobialtherapyafteronsetofhypotensioninsepticshockassociatedwithincreasedmortality
(level2[midlevel]evidence)
antibioticselectionshouldbebasedonpresumedsource,patient'spriormicrobiologydata,andlocalresistancepatterns
designateorderinwhichantibioticsshouldbegiven(typicallyagentswithactivityagainstgramnegativeorganismsgiven
first)ifcandidemiasuspectedstartappropriateantifungaltherapy
planforsourcecontrol(forexample,ifintravascularcatheter/accessdeviceisapotentialsource,removepromptly)
considerimagingwithgoalforinterventionwithin12hoursifneeded(forexample,abscessdrainage)
resuscitationphase(first6hours)
continuevolumeresuscitationifhypotensionortissuehypoperfusionpersistsdespiteinitialresuscitationefforts
continuedfluidresuscitationshouldbeguidedbyfrequentreassessmentofhemodynamicstatus(SCCMBestpractice
statement)including
clinicalexamination
physiologicvariables(heartrate,bloodpressure,arterialoxygensaturation,respiratoryrate,temperature,urineoutput)
otherinvasiveandnoninvasivemonitoringasavailable
dynamicvariablessuggestedoverstaticvariablesforpredictionoffluidresponsiveness(SCCMWeakrecommendation,Low
qualityevidence)
furtherhemodynamicassessment(suchascardiacfunctionmonitoring)recommendedtodeterminetypeofshockif
diagnosisisnotclearafterclinicalassessment(SCCMBestpracticestatement)
targetmeanarterialpressureof65mmHginpatientswithsepticshockrequiringvasopressors(SCCMStrong
recommendation,Moderatequalityevidence)
initiatevasopressortherapyviacentralaccessifhypotensionortissuehypoperfusionpersistsdespiteadequatevolume
resuscitation

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norepinephrineisstandardfirstlinepressorforcentraladministration(SCCMStrongrecommendation,Moderatequality
evidence)
consideradditionofvasopressin(upto0.03units/minute)ifnorepinephrinerequirementisrising(SCCMWeak
recommendation,Moderatequalityevidence)
epinephrinemayalsobeaddedtovasopressintoraisemeanarterialpressure(SCCMWeakrecommendation,Lowquality
evidence)
considerdobutamineforongoinghypoperfusiondespiteadequateintravascularvolumerepletionandvasopressoruse(SCCM
Weakrecommendation,Lowqualityevidence),butreduceordiscontinueincaseofworseninghypotensionorarrhythmia
considercorticosteroidsinpatientswithsepticshockonlyifhemodynamicstabilitynotachievedwithadequatefluid
resuscitationandvasopressorsupport(SCCMWeakrecommendation,Lowqualityevidence)
typicaldosingishydrocortisone200mg/dayIVascontinuousinfusion(SCCMWeakrecommendation,Lowqualityevidence)
or
50mgIVevery6hours(commondoseusedintrialsofpatientswithsepsis)
adjunctivecare
transfusionifhemoglobin(Hgb)<7g/dL(assumingabsenceofmyocardialischemia,severehypoxemia,acutehemorrhage,or
ischemicheartdisease)(SCCMStrongrecommendation,Highqualityevidence)
glucosecontrolwithinsulindriptokeepserumglucose180mg/dL(10mmol/L)and110mg/dL(6.1mmol/L)(SCCM
Strongrecommendation,Highqualityevidence)
forintubatedpatients,minimizesedation(SCCMBestpracticestatement)anduseweaningprotocol(SCCMStrong
recommendation,Moderatequalityevidence)
renalreplacementtherapywithintermittenthemodialysisorcontinuousvenovenoushemofiltration(lattermaybeeasierto
manageinhemodynamicallyunstablepatients)maybeneededinpatientswithacutekidneyinjury(SCCMWeak
recommendation,Moderatequalityevidence)
deepveinthrombosis(DVT)prophylaxisisrecommended(SCCMStrongrecommendation,Moderatequalityevidence)
stressulcerprophylaxiswithhistamine2receptorantagonistorprotonpumpinhibitorrecommendedforpatientswithrisk
factorsforgastrointestinalbleeding(SCCMStrongrecommendation,Lowqualityevidence)
nutritioninitiateenteralnutritionearlyinpatientswhocanbefedenterally(SCCMStrongrecommendation,Moderatequality
evidence)
seeSepsistreatmentinadultsfordetails
ComplicationsandPrognosis

Complications:
disseminatedintravascularcoagulation(DIC)(AnnuRevPathol20116:19)
acuterespiratorydistresssyndrome(ARDS)(5)
acuterenalfailure(5)
cardiomyopathy(CurrCardiolRev2011Aug7(3):163)
hypoxichepatitis(ischemichepatitisor"shockliver")(LiverInt2012Aug32(7):1039 EBSCOhostFullText)
multipleorgandysfunction/failure(4,5)
criticalillnessmyopathyandpolyneuropathy(LancetNeurol2011Oct10(10):931)
sepsisassociatedencephalopathy(NatRevNeurol2012Oct8(10):557)
about15%ofsepsispatientsadmittedtoICUmayacquirenewinfection,mostcommonlycatheterrelated
bloodstreaminfectionandpneumonia
basedonprospectivecohortstudy
1,504patients(medianage62years)with1,719intensivecareunit(ICU)admissionslasting>48hourswereevaluated
patientswithinfectiononsetfrom24to48hoursafteradmissionwereexcluded
334ICUacquiredinfectionsoccurredduring232admissions(13.5%),withmostcommoninfections
catheterrelatedbloodstreaminfection(26.3%ofinfections)
pneumonia(25.4%ofinfections)
abdominalinfection(15.3%ofinfections)
factorsassociatedwithincreasedriskofICUacquiredinfectioninmultivariateanalysisincluded
initiationofmechanicalventilationduringadmission(hazardratio[HR]6.22,95%CI1.5425.17)
centralvenouscatheterplacementduringadmission(HR2.63,95%CI1.534.53)
AcutePhysiologyandChronicHealthEvaluation(APACHE)IVscore100205(HR1.86,95%CI1.182.92)
chronicrespiratoryinsufficiency(HR1.44,95%CI1.052.99)
malesex(HR1.31,95%CI11.73)
ICUmortality
20.9%overall
35.8%inpatientswithICUacquiredinfection
15.5%inpatientswithoutICUacquiredinfection(p<0.001vs.patientswhoacquiredinfection)
ReferenceJAMA2016Apr12315(14):1469,editorialcanbefoundinJAMA2016Apr12315(14):1457

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adrenalfailurecommoninsepticshock
basedonprospectivecohortstudy
102patients>18yearsoldwithsepticshockandnoprevioussteroidusewereevaluated
23patients(22.5%)hadadrenalfailuredefinedasbaselineserumcortisol10mcg/dL(275.9nmol/L)orincreaseinserum
cortisolof9mcg/dL(248.3nmol/L)1hourafterbeinggivencorticotropin249mcg
ReferenceCritCare200610(5):R149fulltext
multipleorganfailureassociatedwithincreasedmusclelossincriticallyilladults
basedonprospectivecohortstudy
63patients(meanage55years)inintensivecareunitwithcriticalillness(49.2%withsepsisand25.4%withtrauma)were
followedupto10days
multipleorganfailurein75%
musclelossassessedbyultrasoundofrectusfemoris
meanmusclelossat7daysafterintensivecareadmission15.7%inpatientswithmultipleorganfailurevs.3%inpatientswith
singleorganfailure(p<0.001)
ReferenceJAMA2013Oct16310(15):1591,correctioncanbefoundinJAMA2014Jan12311(6):625,editorialcanbefound
inJAMA2013Oct16310(15):1569
Prognosis:
Mortality:
inhospitalmortality
inhospitalmortality11.7%19.5%inpatientswithhealthcareassociatedsepsisinUnitedStates
basedonretrospectivecohortstudy
69millionhospitaldischargesinUnitedStatesfrom1998to2006evaluated
inhospitalmortality
19.5%inanalysisof108,610patientswithhealthcareassociatedsepsisfollowinginvasivesurgery
11.7%16%inanalysisof384,640patientswithsepsisclassifiedashealthcareassociatedwhodidnothaveinvasive
surgery
ReferenceArchInternMed2010Feb22170(4):347,editorialcanbefoundinArchInternMed2010Feb22170(4):353
inhospitalmortality18.4%inpatientswithseveresepsisin2012inAustraliaandNewZealand,downfrom35%
in2000
basedonretrospectivecohortstudy
101,064patientswithseveresepsisinintensivecareunitsinAustraliaandNewZealandfrom20002012wereanalyzed
inhospitalmortalityin12,512patientswithseveresepsisin2012
18.4%overall
14.2%inpatientswithoutsepticshock
22%inpatientswithsepticshock
14%inpatientswithoutcomorbidities(asdefinedbyAcutePhysiologyandChronicHealthEvaluation)
26.4%inpatientswithcomorbidities
in2000,inhospitalmortalitywas35%overallinpatientswithseveresepsis
ReferenceJAMA2014Apr2311(13):1308,editorialcanbefoundinJAMA2014Apr2311(13):1295
hospitalmortalityincreaseswithincreasingstageofsepsis
basedonprospectivecohortstudy
3,608intensivecareunitpatientsinEuropeanSepsisStudycategorizedashavinginfectionwithorwithoutsystemic
inflammatoryresponsesyndrome(SIRS),severesepsis,orsepticshockonfirstdayofinfection
crudeoverallhospitalmortality40%
mortalitybysepsisstage
25.5%in584patientswithinfectionwithoutSIRS
25.5%in1,063patientswithsepsis(infectionwithSIRS)
40.9%in827patientswithseveresepsis
60.5%in1,134patientswithsepticshock
ReferenceAmJRespirCritCareMed2003Jul1168(1):77
DynaMedcommentary mortalityhasdeclinedsincethetimeofthisstudythe90daymortalitywasestimatedatabout
45%amonghospitalizedpatientswithseveresepsisorsepticshockbetween2008and2013(CritCareMed2017
Feb45(2):241)
sepsisassociatedwithincreasedriskoflatemortality
basedoncohortstudy
3,029adults65yearsoldintheUnitedStatesHealthandRetirementStudybetween1998and2008wereevaluatedforlate
mortality(mortalitybetween31daysand2years)
960patientshospitalizedwithsepsis
777adultsnotcurrentlyhospitalized

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788patientshospitalizedwithnonsepsisinfection
504patientshospitalizedwithacutesterileinflammatorycondition
patientswithsepsiswerematchedonbaselinecharacteristicstoadultsinothercohorts
inpatientswithsepsis
30daymortality25.4%(95%CI22.7%28.1%)
90daymortality35.3%(95%CI32.3%38.2%)
180daymortality41.3%(95%CI38.3%44.3%)
1yearmortality48.5%(95%CI45.4%51.6%)
2yearmortality56.5%(95%CI53.5%59.6%)
patientswithsepsisassociatedwithincreasedlatemortalitycomparedto
adultsnotinhospital(absoluteincrease22.1%,95%CI17.5%26.7%)
patientshospitalizedfornonsepsisinfection(absoluteincrease10.4%,95%CI5.4%15.4%)
patientshospitalizedforsterileinflammatoryconditions(absoluteincrease16.2%,95%CI10.2%22.2%)
ReferenceBMJ2016May17353:i2375fulltext
6monthmortalityabout33%inpatientswithseveresepsiswholivedindependentlypriortohospitalization
basedoncohortanalysisofdatafrom2randomizedtrials
2,130patientswithseveresepsisfromACCESSandPROWESSSHOCKtrialswereevaluated612monthsaftersepsis
hospitalization
allpatientswerelivingathomeindependentlypriortosepsishospitalization
outcomesat6months
mortality32.8%
inabilitytoliveindependentlyinabout40%
qualityoflifemeasuredat6monthsin1,060patients
mobilityproblemsin37%
problemsperformingusualactivitiesin42.7%
problemsperformingselfcareactivitiesin20.5%
outcomesat1yearinpatientsfromACCESStrial
1yearmortality37.2%
inabilitytoliveindependentlyin31%
qualityoflifemeasuredat1yearin448patientsinACCESSstudy
mobilityproblemsin31.7%
problemsperformingusualactivitiesin32.3%
problemsperformingselfcareactivitiesin14.7%
factorsassociatedwithincreasedriskofmobilityandselfcareproblemsat6monthsinmultivariateanalysesincludedolder
age,ventilatorsupportfor>14days,anddialysisfor>14days
ReferenceCritCareMed2016Aug44(8):1461
Timetoappropriatetherapy:
longertimetoantimicrobialtherapyassociatedwithincreasedmortality(level2[midlevel]evidence)
eachhourofdelayofantimicrobialtherapyassociatedwithincreasedinhospitalmortalityinpatientswithsevere
sepsisandsepticshock(level2[midlevel]evidence)
basedonretrospectivecohortstudy
28,150patientswithseveresepsisandsepticshockfromJanuary2005toFebruary2010in165intensivecareunits(ICUs)
inEurope,theUnitedStates,andSouthAmericaevaluated
17,990patientswhoreceivedantibioticsandhaddataavailableontimingofadministrationwereincludedinanalysis
overallinhospitalmortality29.7%
timetofirstantibioticdefinedasdifferencebetweentimeofpresentationandfirstantibioticadministration

AssociationBetweenTimetoFirstAntibioticandMortality:

TimetoFirstAntibiotic HospitalMortality AdjustedOddsRatio


01hours 32% 1(reference)

12hours 28.1% 1.07(95%CI0.971.18)

23hours 28.6% 1.14(95%CI1.021.26)

34hours 29.8% 1.19(95%CI1.041.35)

45hours 32.5% 1.24(95%CI1.061.45)

56hours 36.6% 1.47(95%CI1.221.76)

>6hours 39.6% 1.52(95%CI1.361.7)

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inlogisticregressionanalysisadjustedforsepsisseverityscore,ICUadmissionsource,andgeographicregion,hospital
mortalityrisksteadilyincreasedfrom24.6%inpatientsreceivingantibioticswithinfirsthourto33.1%inpatientswith>6
hourdelay
ReferenceCritCareMed2014Aug42(8):1749,editorialcanbefoundinCritCareMed2014Aug42(8):1931,commentary
canbefoundinCritCareMed2014Dec42(12):e802,CritCareMed2015Mar43(3):e102
startingappropriateantibioticswithin1hourassociatedwithlowermortalityinpatientswithseveresepsisor
septicshock(level2[midlevel]evidence)
basedonretrospectivecohortstudy
261patientswithseveresepsisorsepticshockatacademictertiarycarecenterhadearlygoaldirectedtherapystartedin
emergencydepartment
inhospitalmortality31%
mediantimefromtriagetoantibiotics119minutes,mediantimefromqualificationforearlygoaldirectedtherapyto
antibiotics42minutes
timefromtriagetoappropriateantibiotics1hourassociatedwithlowermortality(19.5%vs.33.2%,p=0.02)
timefromqualificationtoappropriateantibiotics1hourassociatedwithlowermortality(25%vs.38.5%,p=0.03)
ReferenceCritCareMed2010Apr38(4):1045,editorialcanbefoundinCritCareMed2010Apr38(4):1211,commentary
canbefoundinCritCareMed2011Apr39(4):923
eachhourofdelayofantimicrobialtherapyafteronsetofhypotensioninsepticshockassociatedwithincreased
mortality(level2[midlevel]evidence)
basedonretrospectivecohortstudy
2,154adultswithsepticshockin14intensivecareunitsand10hospitalsinUnitedStatesandCanadaevaluated
survivalrate79.9%ifeffectivetreatmentadministeredwithin1hourofdocumentedhypotension
delayofeffectivetherapyassociatedwithincreasedriskofinhospitalmortality
adjustedoddsratio1.119perhourdelay(95%CI1.1031.136)
survivaldecreased7.6%witheachhoureffectivetreatmentwasdelayed
ReferenceCritCareMed2006Jun34(6):1589,editorialcanbefoundinCritCareMed2006Jun34(6):1819,commentary
canbefoundinCanJAnaesth2006Nov53(11):1157
delayingantibioticadministrationuntilshockrecognitionassociatedwithincreasedmortality(level2[midlevel]
evidence)
basedonsecondaryanalysisofrandomizedtrialwithoutblinding
291patientsfromEMShockNettrialwithseveresepsisandevidenceofhypoperfusionorsepticshockwhoreceivedfirstdose
ofantibioticsafterpresentationtohospitalwereanalyzed
inhospitalmortality19%
59%receivedantibioticsaftershockrecognition
mortality23.8%inpatientswhoreceivedantibioticsaftershockrecognitionvs.11.8%inpatientswhoreceivedantibiotics
beforeshockrecognition(p<0.05,NNH8)
nosignificantincreaseinmortalitywithhourlydelaysinantibioticadministrationupto6hoursaftertriage
ReferenceCritCareMed2011Sep39(9):2066fulltext,editorialcanbefoundinCritCareMed2011Sep39(9):2184,
commentarycanbefoundinCritCareMed2012Mar40(3):1035
similartrendinmortalityfoundinsystematicreviewof11studies(including4above)evaluatingtimingofantibiotic
administrationin16,178adultswithseveresepsisorsepticshock,althoughstatisticalsignificancenotmetthismayberelated
toexclusionofalargenumberofpatientswhodidhaveexplicitenoughrecordsontiming(CritCareMed2015Sep43(9):1907)
norandomizedtrialsidentifiedcomparingearly(<1hourafterpresentationtoemergencydepartment)vs.late
administrationofbroadspectrumantibioticsinadultswithseveresepsis
basedonCochranereview
ReferenceCochraneDatabaseSystRev2010Oct6(10):CD007081
delayedinitiationofeffectiveantimicrobialtherapyassociatedwithincreasedriskofhospitalmortality(level2[mid
level]evidence)
basedonretrospectivecohort
5,715adults(meanage63years)withsepticshockhadappropriatenessofinitialtherapyevaluated
appropriateantimicrobialtherapyinitiatedin80.1%
overallsurvival43.7%
survivalrate52%withpromptstartingofappropriatetherapyvs.10.3%withdelayedinitiationofeffectiveantimicrobialtherapy
(adjustedoddsratio8.99,p<0.0001)
ReferenceChest2009Nov136(5):1237
Factorsassociatedwithmortality:
newonsetatrialfibrillationinpatientswithseveresepsisassociatedwithincreasedriskofinhospitalstrokeand
mortality
basedonretrospectivecohortstudy
3,144,787hospitalizedadultsevaluatedforseveresepsisandnewonsetatrialfibrillation(AF)

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severesepsisdefinedbyvalidatedICD9ClinicalModification(ICD9CM)code995.92andnewonsetAFdefinedasAFthat
occurredduringhospitalstay
49,082patientshadseveresepsis
severesepsisassociatedwithincreasedriskofdevelopingAFcomparedtopatientswithoutseveresepsis(5.9%vs.0.65%,p
<0.001)
comparingseveresepsiswithvs.withoutnewonsetAF
inhospitalstroke2.6%vs.0.6%(p<0.001)
inhospitalmortality56%vs.39%(p<0.001)
ReferenceJAMA2011Nov23306(20):2248fulltext,editorialcanbefoundinJAMA2011Nov23306(20):2264
blackraceassociatedwithincreasedriskofsepsisseverityandmortality
basedonretrospectivecohortstudy
2,261,857infectionrelatedhospitaldischargesevaluated
16.8%hadseveresepsis
comparingageandsexstandardizedratesinblackpatientsvs.whitepatients
severesepsis9.4per1,000populationvs.5.6per1,000population(p<0.001)
mortality1.8per1,000populationvs.1per1,000population(p<0.001)
authorsstatethatmultiplefactors,suchasaccesstomedicalcare,smokingstatus,alcoholconsumption,andnutritionalstatus
maycontributetodifferencesamongraces
ReferenceJAMA2010Jun23303(24):2495
commentaryindicatesthatdifferencesinHIVinfectionbetweenracesmayalsohavecontributedtoincreasedriskofsepsis
(JAMA2010Oct13304(14):1556)
cardiovascularfailure,preexistingterminalillness,respiratorycompromise,tachycardia,anddecreasedplatelet
countassociatedwithincreasedmortalityinelderlypatientsadmittedintoemergencydepartmentforinfection
basedonsecondaryanalysisofderivationandvalidationstudy
3,940patients>65yearsoldpresentingtoemergencydepartmentwhowereadmittedtohospitalwithsuspectedinfection
includedinderivationcohort,2,015similarpatientsincludedinvalidationcohort
mortality6%inderivationcohort,7%invalidationcohort
mortalityriskfactorsidentifiedinderivationcohort
cardiovascularfailure(systolicbloodpressure[SBP]<90mmHgdespitefluidchallengeorlactate4mmol/L[36mg/dL])
(oddsratio[OR]9,95%CI4.717)
preexistingterminalillness(OR5.7,95%CI2.215)
respiratorycompromise(breathingrate>20breaths/minuteorhypoxemia)(OR4,95%CI1.79.4)
tachycardia(heartrate120beats/minute)(OR3.2,95%CI1.66.3)
plateletcount<150,000/mm3(OR2.7,95%CI1.35.6)

MortalitybyNumberofRiskFactors:

NumberofRiskFactors DerivationCohort Validation


Cohort
0 0.51% 2%

1 3.1% 6.8%

2 14% 13.9%

3 47% 27.4%
ReferenceJAmGeriatrSoc2009Jul57(7):1184 EBSCOhostFullText,commentarycanbefoundinJAmGeriatrSoc
2010Jan58(1):194 EBSCOhostFullText
riskofinhospitalmortalitymaydifferbyinfectionsourceinadultswithsepticshock
basedonretrospectivecohortstudy
7,974adults(meanage63years)withsepticshockwereevaluated
overallinhospitalmortality52%
inanalysesadjustedforpredisposinganddownstreamfactors
increasedriskofinhospitalmortalitysignificantlyassociatedwithischemicbowelandcentralnervoussysteminfections,
disseminatedinfections,andotherintraabdominalinfections
decreasedriskofinhospitalmortalitysignificantlyassociatedwithobstructiveuropathyassociatedurinarytractinfection,
enterocolitis/diverticulitis,pyelonephritis,cholecystitis/cholangitis,andintravascularcatheterinfections
ReferenceAmJRespirCritCareMed2014May15189(10):1204,editorialcanbefoundinAmJRespirCritCareMed2014
May15189(10):1156
thrombocytopeniaatonsetofsepsisin Staphylococcusaureus bacteremiaassociatedwithincreasedriskof30day
mortality

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basedonretrospectivecohortstudy
1,052adultswithS.aureus bacteremiaevaluated
thrombocytopenia(plateletcount<150x109/L)atonsetofsepsisin22.3%
30dayallcausemortalityin56.2%withthrombocytopeniavs.34.4%withoutthrombocytopenia(p<0.001)
increasedriskofmortalityproportionaltodegreeofthrombocytopenia
ReferenceMayoClinProc2011May86(5):389fulltext
higherlactateclearanceassociatedwithreducedmortalityinpatientswithseveresepsisorsepticshock
basedonsystematicreviewlimitedbyclinicalheterogeneity
systematicreviewof3randomizedtrialsand12observationalstudiesevaluatinglactateclearanceincriticallyillpatients
definitionoflactateclearancevariedbetweenstudies
overallmortality23%54.3%in5studieswithpatientswithseveresepsisorsepticshock
higherlactateclearanceassociatedwithreducedmortalityinanalysisof5studieswith627patientswithsepsisorsepticshock
riskratio0.41,95%CI0.280.6
resultlimitedbysignificantheterogeneity
ReferenceCritCareMed2014Sep42(9):2118,editorialcanbefoundinCritCareMed2014Sep42(9):2149
severehyperglycemiaatadmissionassociatedwithincreased30daymortalityinpatientswithsepsis
basedonprospectivecohortstudy
987patientshospitalizedwithsepsiswhohadadmissionglucoselevels>70mg/dLevaluated
519(52.6%)hadnormalglucoselevel(glucoselevel71140mg/dL)
267(27.1%)hadmildhyperglycemia(glucoselevel144199mg/dL)
201(20.4%)hadseverehyperglycemia(glucoselevel200mg/dL)
severehyperglycemiaassociatedwithincreased30daymortality
overall(adjustedhazardratio[HR]1.66,95%CI1.242.23)
inpatientswithoutdiabetes(adjustedHR1.65,95%CI1.122.42)
inpatientswithdiabetes(adjustedHR1.91,95%CI1.013.62)
mildhyperglycemianotassociatedwithincreased30daymortality
ReferenceCritCareMed2016Jul44(7):1338,commentarycanbefoundinJThoracDis2016Jul8(7):E575,JThoracDis
2016Jul8(7):E621,JThoracDis2016Jul8(7):E567,JThoracDis2016Jul8(7):E581
solidorgantransplantassociatedwithreducedmortalityinpatientswithbacteremicsepsis
basedoncohortstudy
123solidorgantransplantrecipientswithcultureprovensepsiswerecomparedto246nontransplantpatientswithsepsis
inmultivariateanalysisadjustingforclinicalpresentation,illnessseverity,andinfectiontype,solidorgantransplantassociated
withdecreasedmortality
at28days(hazardratio[HR]0.22,95%CI0.090.54)
at90days(HR0.43,95%CI0.20.89)
ReferenceClinInfectDis2015Jan1560(2):216
Predictionmodels:
predictionmodelsbasedonpredisposition,insult/infection,response,andorgandysfunction(PIRO)
whilebothmodelsdetailedbelowgobythePIROacronym,scoringmethodsdiffer
PIROriskmodelpredictshospitalmortalityinpatientswithseveresepsis(level1[likelyreliable]evidence)
basedonprognosticcohortstudywithindependentderivationandvalidationcohorts
PIROriskmodelderivedfrom840patientsinplaceboarmofPROWESStrial
PIROriskmodelvalidatedin10,610patients>18yearsoldwithseveresepsisinPROGRESSglobalregistry,excluding
patientstreatedwithdrotrecoginalfa(activatedproteinC)
PIROscoredeterminedby4factors
Predispositionranges04points
0pointsifage<46years
1pointifage4664yearswithnochronicliverdisease
2pointsifage6485yearswithnochronicliverdiseaseandnocongestivecardiomyopathy
3pointsifage4664yearswithchronicliverdiseaseorage6485yearswithcongestivecardiomyopathy
4pointsifage>85yearsorage6485yearswithchronicliverdisease
Insult/Infectionranges04points
0pointsifgramnegativecommunityacquiredurinarytractinfection
1pointifnongramnegativecommunityacquiredurinarytractinfection
2pointsifcommunityacquiredinfectionotherthanurinarytractinfection,ornosocomialgrampositiveinfection
3pointsifnongrampositivenosocomialinfectionornonabdominalnosocomialfungalinfection
4pointsifabdominalnosocomialfungalinfection
Responseranges01points
0pointsifnotachycardiaand/ornotachypnea
1pointiftachycardiaplustachypnea

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Organdysfunctionranges04points
0pointsif2organfailures
1pointifhepaticfailureplus2otherorganfailures
2pointsif3organfailures(otherthanhepaticfailure)
3pointsif4organfailures
4pointsif5organfailures
hospitalmortalitybyPIROscore
PIROScore HospitalMortalityinValidationCohort
03points 20.6%

4points 31%

5points 40.1%

6points 48.5%

7points 56.8%

8points 63.9%

9points 72.2%

1013points 79.9%

Abbreviations:PIRO,Predisposition,Insult/infection,Response,andOrgandysfunction.
ReferenceCritCareMed2009Apr37(4):1329
PIROstagingscorepredictshospitalmortalityinemergencydepartmentpatientswithsuspectedinfection(level1
[likelyreliable]evidence)
basedonprognosticcohortstudywithindependentderivationandvalidationcohorts
derivationcohortincluded2,132patients>18yearsoldwhowereadmittedtoemergencydepartmentwithsuspected
infection
validationcohort1included4,618similarpatientsandvalidationcohort2included1,004similarpatients
PIROstagingscoredevelopedbasedon4factorsinderivationcohort
predisposition
0pointsifage65years
1pointifage6580years
2pointsifage>80years
1pointifchronicobstructivepulmonarydisease(COPD)
2pointsifliverdisease
2pointsifnursinghomeresident
1pointifmalignancywithoutmetastases
2pointsifmalignancywithmetastases
infection
4pointsifpneumonia
0pointsifskin/softtissueinfection(SSTI)
2pointsifanyotherinfection
response
3pointsifrespiratoryrate>20breaths/minute
1pointifbands>5%
2pointsifheartrate>120beats/minute
organfailure
2pointsifbloodureanitrogen(BUN)>20mg/dL
3pointsifrespiratoryfailure/hypoxemia
3pointsiflactate>4mmol/L(36mg/dL)
4pointsifSBP<70mmHg
2pointsifSBP7090mmHg
0pointsifSBP>90mmHg
2pointsifplateletcount<150,000/mm3
predictiveperformanceforhospitalmortalityinvalidationcohorts
PIROScore MortalityinValidationCohort1 MortalityinValidationCohort2
<5points 0.3% 0.3%

59points 3% 3.7%

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PIROScore MortalityinValidationCohort1 MortalityinValidationCohort2


1014points 10.4% 8.4%

1519points 20.1% 32%

20points 38.9% 40%

Abbreviations:PIRO,Predisposition,Insult/infection,Response,andOrgandysfunction.
ReferenceCritCareMed2011Feb39(2):322,editorialcanbefoundinCritCareMed2011Feb39(2):408
MortalityinEmergencyDepartmentSepsis(MEDS)scorepredicts28daymortalityinpatientswithsystemic
inflammatoryresponsesyndrome(level1[likelyreliable]evidence)
basedonvalidationcohortstudy
385patientsaged18100yearswhopresentedtoemergencydepartment,metcriteriaforSIRS,andwereadmittedtohospital,
evaluated
scorebasedon
terminalillness(6points)
tachypneaorhypoxemia(3points)
septicshock(3points)
plateletcount<150,000cells/mm3(3points)
bandcountaspercentageoftotalwhitebloodcellcount>5%(3points)
age>65years(3points)
lowerrespiratoryinfection(2points)
nursinghomeresidence(2points)
alteredmentalstatus(2points)
mortalitybyMEDSscore
MEDSScore MortalityRate
04points 0.6%(95%CI0%3%)

57points 5%(95%CI1%13%)

812points 19%(95%CI11%29%)

1315points 32%(95%CI15%54%)

>15points 40%(95%CI12%74%)

Abbreviations:MEDS,MortalityinEmergencyDepartmentSepsis.
ReferenceCritCareMed2008Feb36(2):421,editorialcanbefoundinCritCareMed2008Feb36(2):625,commentarycan
befoundinCritCareMed2008Sep36(9):2715
PIROscoremayhavebetterperformancethanMEDSscoreforpredictionof30daymortalityinemergency
departmentpatientswithsepsis,septicshock,orinfectionwithoutorganfailure(level2[midlevel]evidence)
basedonvalidationcohortstudywithborderlinestatisticalsignificance
240patientsinemergencydepartmentwithsepsis,septicshock,orinfectionwithoutorgandysfunctionwereevaluatedby
PIRO,MEDS,andSequentialOrganFailureAssessment(SOFA)scores
30daymortality20%
forpredictionof30daymortality
PIROscorehadnonsignificantlybetterpredictiveperformancecomparedtoMEDSscore(p=0.064)
PIROscorehadbetterpredictiveperformancecomparedtoSOFAscore(p=0.01)
nosignificantdifferenceinpredictiveperformancecomparingMEDSscoretoSOFAscore
ReferenceAcadEmergMed2014Nov21(11):1257
risk,injury,failure,loss,andendstagekidneydisease(RIFLE)classesmaypredicthospitalmortalityinpatientswith
sepsis(level2[midlevel]evidence)
basedonretrospectivecohortstudy
182patientswithsepsisadmittedtoinfectiousdiseaseintensivecareunitevaluated
68patients(37.4%)hadacuterenalfailure
RIFLEclassificationmaybebasedonglomerularfiltrationrate(GFR)orurineoutputcriteria
riskofrenaldysfunction
GFRcriteriaincreasedserumcreatinine1.5foldorGFRdecrease>25%
urineoutputcriteriaurineoutput<0.5mL/kg/hourfor6hours
injurytokidney
GFRcriteriaincreasedserumcreatinine2foldorGFRdecrease>50%
urineoutputcriteriaurineoutput<0.5mL/kg/hourfor12hours
failureofkidneyfunction
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GFRcriteriaincreasedserumcreatinine3foldorGFRdecrease>75%orserumcreatinine>4mg/dL(350mcmol/L)in
settingofacuteincreaseofatleast0.5mg/dL(44mcmol/L)
urineoutputcriteriaurineoutput<0.3mL/kg/hourfor24hours(oliguria)oranuriafor12hours

RIFLEClassandHospitalMortality:

RIFLEClass NumberofPatients HospitalMortality


Norenalfailure 114 9.6%

Risk 11 27.3%

Injury 21 28.6%

Failure 36 55%

Abbreviation:RIFLE,Risk,Injury,Failure,Loss,andEndstagekidneydisease.
ReferenceCritCare2007Apr511(2):408fulltext
AdherencetoSurvivingSepsisCampaignguidelines:
SurvivingSepsisCampaignguidelinesassociatedwithreducedmortality(level2[midlevel]evidence)
basedon3observationalstudies
compliancewithSurvivingSepsisCampaignguidelinesassociatedwithdecreasedmortality(level2[midlevel]
evidence)
basedonprospectivecohortstudy
29,470patientstreatedforseveresepsisorsepticshockevaluatedforcompliancewithresuscitationandmanagement
bundlesfromSurvivingSepsisCampaignguidelinesfrom2005to2012
forresuscitationbundle
highcompliancein61%
hospitalmortality29%inhighcompliantgroupvs.38.6%inlowcompliantgroup(p<0.001)
formanagementbundle
highcompliancein53%
hospitalmortality32.3%inhighcompliantgroupvs.33.4%inlowcompliantgroup(p=0.04)
ReferenceCritCareMed2015Jan43(1):3
SurvivingSepsisCampaignguidelinesbasededucationassociatedwithreducedmortality(level2[midlevel]
evidence)
basedonbeforeandafterstudyofpatientsinintensivecareunitsinSpain
854patientsevaluatedpreinterventionand1,465patientsevaluatedpostintervention
interventionwasnationaleducationalprogrambasedonSurvivingSepsisCampaignguidelines
hospitalmortalityreducedfrom44%preinterventionto39.7%postintervention(p=0.04)
ReferenceJAMA2008May21299(19):2294,editorialcanbefoundinJAMA2008May21299(19):2322,commentarycan
befoundinJAMA2008Oct15300(15):1762
noncompliancewithSurvivingSepsisCampaignguidelinesassociatedwithincreasedmortality(level2[midlevel]
evidence)
basedonprospectivecohortstudywithoutassessmentofpatientcharacteristicsbetweengroups
101consecutiveadultstreatedforseveresepsisorsepticshockevaluatedforcompliancewith6hourand24hoursepsis
carebundlesfromSurvivingSepsisCampaignguidelines
for6hourbundle
rateofcompliance52%
hospitalmortality23%incompliantgroupvs.49%innoncompliantgroup(p=0.01)
for24hourbundle
rateofcompliance30%
hospitalmortality29%incompliantgroupvs.50%innoncompliantgroup(notsignificant)
ReferenceCritCare20059(6):R764fulltext,editorialcanbefoundinCritCare20059(6):653
Biomarkers:
increasingbloodlactateassociatedwithincreased28daymortalityinpatientswithsepticshock
basedonretrospectivecohortstudy
665patientswithsepticshockwhohadarteriallactatemeasuredwithinmean18hoursafteronsetwereanalyzed
septicshockdefinedby2diagnosticcriteriaforSIRS,provenorsuspectedinfection,1neworgandysfunctionbyBrussels
criteria,andhypotensiondespiteadequatefluidresuscitation
28daymortalitybyquartileofbloodlactateconcentration
Quartile MedianLactate 28dayMortality* HazardRatio(vs.Quartile
Concentration 1)

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1 1.1mmol/L(9.91mg/dL) 27% Notapplicable

2 1.8mmol/L(16.22mg/dL) 41% 1.78

3 3mmol/L(27mg/dL) 38% 1.65

4 6.7mmol/L(60.37mg/dL) 59% 3.5

*Estimatedfromfigure.
similartrendformortalitywasobservedinsecondcohortof469patientswhohadarteriallactatemeasuredwithin4hoursof
onset
ReferenceShock2012Jul38(1):4
otherbiomarkersmayaidinprognosisbutareexperimentalandstillconsideredtobeinpreclinicalphasesofdevelopment
decisiontreeusingmultiplebiomarkershasmoderatepredictiveperformancefor28daymortalityinadultswith
septicshock(level1[likelyreliable]evidence)
basedonprognosticcohortstudywithindependentderivationandvalidation
derivationcohortincluded672adultspresentingtointensivecareunitwithsepticshockandvalidationcohortincluded209
similaradults
28daymortality31%inderivationcohortand42%invalidationcohort
decisiontreederivedusingserumbiomarkersandotherriskfactorssignificantlyassociatedwith28daymortalityinderivation
cohort(refertofulltextfordetails)
CCchemokineligand3
CCchemokineligand4
heatshockprotein70kDa1B
interleukin1alpha
interleukin8
granzymeB
lactate
age
presenceofchronicdisease
forpredictionof28daymortalityinvalidationcohort,decisiontreehad
sensitivity85%
specificity60%
positivepredictivevalue61%
negativepredictivevalue85%
ReferenceCritCareMed2014Apr42(4):781,editorialcanbefoundinCritCareMed2014Apr42(4):974
elevatedcardiactroponinlevelsassociatedwithincreasedriskofmortalityinadultswithsepsis
basedonsystematicreviewofobservationalstudies
systematicreviewof17studiesreportingtroponinlevels(troponinIand/ortroponinT)in1,857adultswithsepsis,severe
sepsis,orsepticshock
60.5%ofpatientshadelevated(positive)troponin
elevatedtroponinassociatedwithincreasedriskofmortalityinanalysisofalltrials(riskratio1.91,95%CI1.652.22)
similarresultsinanalysisofstudiesthatincludedonlypatientswithsepticshockoronlypatientswithsepsis,studiesusing
onlytroponinTlevels,andstudiesusingonlytroponinIlevels
ReferenceHeartLung2015JanFeb44(1):75
reviewofsepsisbiomarkerscanbefoundinCritCare201014(1):R15fulltext
Morbidity:
readmissionwithin90daysinabout43%afterhospitalizationforseveresepsis
basedonretrospectivecohortstudywith2,617patients50yearsold(meanage79years)inUnitedStatesdischargedfrom
hospitalfollowingepisodeofseveresepsis
readmissionwithin90daysin42.6%
mostcommoncausesofreadmission
sepsisin6.4%
congestiveheartfailurein5.5%
pneumoniain3.5%
acuterenalfailurein3.3%
rehabilitationin2.8%
respiratoryfailurein2.5%
ReferenceJAMA2015Mar10313(10):1055
severesepsisinelderlypersonsassociatedwithincreasedriskofcognitiveimpairmentandfunctionaldisability(level
2[midlevel]evidence)

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basedonretrospectivecohortstudy
9,223persons50yearsoldfromMedicaredatabasehadbaselinecognitiveandfunctionalassessmentandwerefollowedfor
8years
5.7%survivedepisodesofseveresepsisandhad1followupassessment
prevalenceofmoderatetoseverecognitiveimpairmentincreased10.6%afterseveresepsis(oddsratio3.34,95%CI1.53
7.25)
severesepsisassociatedwithincreasedfunctionaldisability
mean1.57disabilities(95%CI0.992.15)forpersonswithnolimitationsbeforesepsis
mean1.5newdisabilities(95%CI0.872.12)forpersonswithmildtomoderatelimitationsbeforesepsis
ReferenceJAMA2010Oct27304(16):1787fulltext,editorialcanbefoundinJAMA2010Oct27304(16):1833
priorbacteremiaorsepsisassociatedwithincreased5yearriskofcardiovascularevents
basedonretrospectivecohortstudy
47,009patientshospitalized2timesbetween2008and2012evaluated(156,380totalhospitalizations)
bacteremiaoccurredin4,923hospitalizations(3.1%)among3,932patients
sepsisoccurredin5,544hospitalizations(3.5%)among4,474patients
firstcardiovascularevent(stroke,transientischemicattack,ormyocardialinfarction)occurredin3,501hospitalizations
(2.2%)
factorsassociatedwithincreasedriskoffirstcardiovasculareventinmultivariateanalysis
priorbacteremia(oddsratio[OR]1.52,95%CI1.211.9)
priorsepsisofanyseverity(OR2.39,95%CI1.883.03)
priorsepsis(OR1.99,95%CI1.52.63)
priorseveresepsis(OR3.6,95%CI2.595)
priorsepticshock(OR4.55,95%CI3.585.78)
ReferenceClinInfectDis2016Aug1563(4):495
PreventionandScreening

Prevention:
selectivedecontaminationofdigestivetractandselectiveoropharyngealdecontamination
selectivedecontaminationofdigestivetractassociatedwithdecreaseinmultipleorgandysfunctionsyndromebut
notmortality(level2[midlevel]evidence)
basedonsystematicreviewofmostlymoderatequalitytrials
systematicreviewof7randomizedtrialsevaluatingeffectofselectivedecontaminationofdigestivetractwithparenteraland
enteralantibiotics(vs.placeboorstandardtherapy)onmultipleorgandysfunctionsyndromein1,270criticallyillpatients
selectivedecontaminationgroupassociatedwithdecreasedrateofmultipleorgandysfunctionsyndromeinanalysisof7
studies(oddsratio0.5,95%CI0.340.74)
nosignificantdifferencebetweengroupsin
totalmortalityinanalysisof7studies
multipleorgandysfunctionsyndromerelatedmortalityinanalysisof5studies
ReferenceCritCareMed2010May38(5):1370,editorialcanbefoundinCritCareMed2010May38(5):1386
selectivedigestivedecontaminationaspneumoniaprophylaxisreducesriskofICUmortalityincriticallyillpatients
(level1[likelyreliable]evidence)
basedonsystematicreview
systematicreviewof145randomizedtrialsassessingpneumoniaprophylaxisin37,156criticallyilladultpatientshospitalized
inintensivecareunits(ICUs)
anypneumoniaprophylacticinterventionassociatedwithreducedriskofICUmortality(riskratio0.95,95%CI0.920.99)
digestivedecontaminationassociatedwithreducedriskofmortalityinsubgroupanalysisof10,227patients(riskratio0.84,
95%CI0.760.92)
otherdigestiveorcircuitstrategiestopreventhospitalacquiredpneumonianotassociatedwithreducedriskofmortalityin
subgroupanalyses
ReferenceClinInfectDis2015Jan160(1):64
selectivedigestivetractdecontaminationorselectiveoropharyngealdecontaminationmayreduceriskof
bacteremiaandmightreducemortalityinICUpatientswithorwithoutmechanicalventilation(level2[midlevel]
evidence)
basedonclusterrandomizedtrialwithoutblindingandwithbaselinedifferences
13surgicalandnonsurgicalICUswererandomizedtoprovide1of3treatmentsfor5,939patientswithexpecteddurationof
mechanicalventilation>48hoursorexpectedICUstay>72hours
selectiveoropharyngealdecontaminationincludingtobramycin,colistin,andamphotericinBinoropharynx
selectivedigestivetractdecontaminationincludingselectiveoropharyngealdecontaminationantibioticsinoropharynxand
stomachpluscefotaximeIVfor4days
standardcare

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atbaseline,patientsinselectivedecontaminationgroupsweremoreseverelyillthancontrolswithhigherratesofmechanical
ventilationandadmissiontononsurgicalICUs
92%stayedinICU>72hours

Outcomes:

StandardCare SelectiveOropharyngeal SelectiveDigestiveTract


Decontamination Decontamination
Bacteremia 13% 9%(NNT25)* 7%(NNT17)*

28daymortality 27.5% 26.6% 26.9%

Endotrachealaspirate 15% 10%(NNT20)* 8%(NNT15)*


cultureswithhighlyresistant
microorganisms(insubgroup
with>3dayICUstay)

Abbreviation:ICU,intensivecareunit.

*p<0.05vs.standardcare.
nosignificantdifferencesincrude28daymortality
selectiveoropharyngealdecontaminationandselectivedigestivedecontaminationeachassociatedwithsignificantreduction
in28daymortalitycomparedtostandardcareafteradjustmentforage,sex,acutephysiology,andchronichealthevaluation
(APACHEII)score,intubationstatus,medicalspecialty,studysite,andstudyperiod
References
NEnglJMed2009Jan1360(1):20
LancetInfectDis2011May11(5):372,editorialcanbefoundinLancetInfectDis2011May11(5):337,commentarycan
befoundinLancetInfectDis2012Mar12(3):179
bathingwithchlorhexidineimpregnatedwashclothmaydecreaseriskofhospitalacquiredbloodstreaminfection
(level2[midlevel]evidence)
basedonclusterrandomizedcrossovertrialwithoutintentiontotreatanalysis
12intensivecareandbonemarrowtransplantationunitswererandomizedtobathingwithnorinsechlorhexidine2%
impregnatedwashclothvs.nonantimicrobialwashclothdailyfor6monthsfollowedbycrossovertootherinterventionfor
additional6months
washclothswereusedonallbodysurfacesexcludingface
3unitswithdrewfromtrialorhadlowcomplianceandwereexcludedfromanalyses
7,727patientswhosignedtrialconsentwereincludedinanalyses
primarybloodstreaminfectiondefinedashospitalacquiredbloodstreaminfectiondetected>48hoursafteradmissionwithout
attributablesecondarysourceofinfection
comparingchlorhexidineimpregnatedwashclothvs.nonantimicrobialwashcloth
hospitalacquiredbloodstreaminfections(at>48hoursfromadmission)4.78per1,000patientdaysvs.6.6per1,000
patientdays(p=0.007)
primarybloodstreaminfections3.61per1,000patientdaysvs.5.24per1,000patientdays(p=0.006)
centralcatheterassociatedbloodstreaminfections1.55per1,000catheterdaysvs.3.3per1,000catheterdays(p=0.004)
Staphylococcusaureus
multidrugresistantorganismcolonizations(withmethicillinresistant orvancomycinresistant
Enterococcus )5.1per1,000patientdaysvs.6.6per1,000patientdays(p=0.03)
skinreactionsin2%vs.3.4%(nopvaluereported)
ReferenceNEnglJMed2013Feb7368(6):533,correctioncanbefoundinNEnglJMed2013Jun13368(24):2341
tunnelinginternaljugularcatheterization(separatingcutaneouspuncturesitefromvenouspuncturesiteby>8cm)
decreasesriskofsepsis(level2[midlevel]evidence)
basedonrandomizedtrialwithoutintentiontotreatanalysis
241intensivecareunitpatientsrequiringjugularvenouscatheterfor>48hoursrandomizedtotunneledvs.nontunneled
catheters
tunnelingassociatedwith
decreasedcatheterrelatedsepsis(oddsratio[OR]0.33,95%CI0.130.83)
decreasedcatheterrelatedsepticemia(OR0.23,95%CI0.070.81)
ReferenceJAMA1996Nov6276(17):1416
antimicrobialcoatingsthatappeartoreduceriskofcentralvenouscatheterrelatedbloodstreaminfectioninclude
minocyclinerifampicin(level1[likelyreliable]evidence),chlorhexidinesilversulfadiazine,silver,andheparin(level2
[midlevel]evidence),butantimicrobialcoatingsdonotappeartoreduceriskofsepsisormortality(level2[mid
level]evidence)

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basedonCochranereviewoftrialswithmethodologiclimitations(forcatheterrelatedbloodstreaminfection[CRBSI]with
coatingsotherthanminocyclinerifampicinandforsepsisoutcome)
systematicreviewof57randomizedtrialscomparingantimicrobialcoatedcentralvenouscatheters(CVC)vs.nonantimicrobial
coatedcathetersoralternativeantimicrobialcoatingsinadultsrequiringCVCinhospitalsetting
reviewincluded2highqualitytrialsevaluatingeffectofminocyclinerifampicincoatingsonCRBSI(neithertrialevaluatedeffect
onsepsisormortality)
remainingtrialshad1limitationincluding
unclearornoallocationconcealment
unclearornoblinding
comparingantimicrobialcoatedCVCtostandardCVC
foroutcomeofCRBSI
significantreductionwith
minocyclinerifampicincatheters(riskratio[RR]0.26,95%CI0.130.49)inanalysisof4trialswith1,335catheters
chlorhexidinesilversulfadiazineimpregnatedcatheters(RR0.73,95%CI0.570.94)inanalysisof19trialswith4,886
catheters
silverimpregnatedcatheters(RR0.56,95%CI0.380.82)inanalysisof6trialswith1,587catheters
heparincoatedcatheters(RR0.27,95%CI0.080.95)in1trialwith240catheters
nosignificantdifferencewithsilverplatinumcarbonimpregnatedcathetersinanalysisof4trialswith1,320catheters
nosignificantdifferencesin
sepsisinanalysisof12trialswith3,686catheters
mortalityinanalysisof10trialswith2,643adults
minocyclinerifampicinimpregnatedcathetersassociatedwithdecreasedriskofCRBSIcomparedtochlorhexidinesilver
sulfadiazineimpregnatedcatheters(RR0.11,95%CI0.020.58)inanalysisof2trialswith812catheters
ReferenceCochraneDatabaseSystRev2016Mar16(3):CD007878
intensiveglucosecontrolincriticalcare
intensiveglucosecontrolassociatedwithreducedriskforsepsis(level2[midlevel]evidence)
effectofintensiveglucosecontrolonmortalityhasbeeninconsistent(increased,decreased,ornosignificanteffect)across
randomizedtrialsandsystematicreviews
seeGlucosecontrolincriticalcarefordetails
Socitfranaised'anesthsieetderanimation/Socitderanimationdelanguefranaiseguidelineonpreventionofhospital
acquiredsepsisinintensivecareunitcanbefoundinAnnFrAnesthReanim2009Oct28(10):912[French]
Screening:
hospitalsandhospitalsystemsshouldhaveperformanceimprovementprogramforsepsisthatincludesscreeningforsepsisin
acutelyill,highriskpatients(SCCMBestpracticestatement)
QualityImprovement

Medicare/JointCommissionNationalHospitalInpatientQualityMeasures:
SEP1EarlyManagementBundle,SevereSepsis/SepticShock
measuredasproportionofpatientswithdiagnosisofsepsis,severesepsisorsepticshockwhoreceivedallofthefollowing
initiallactatemeasured
bloodculturesobtainedpriortostartingantibioticsandreceivedwithin6hoursofpresentationofseveresepsis
broadspectrumorotherantibioticsadministered
repeatlactatelevelsperformedonlyifinitiallactateleveliselevated
ifsepticshockpresentreceivedresuscitationwith30mL/kgcrystalloidfluidswithin3hoursofpresentation
ifhypotensionpersistsafterfluidadministration,receivedvasopressorswithin6hoursofpresentation
ifhypotensionpersistsafterfluidadministrationorinitiallactate4mmol/L,reassessmentofvolumestatusandtissue
perfusionreceivedwithin6hoursofpresentationofsepticshock
StudySummariesOnQualityImprovement:
SurvivingSepsisCampaignbasedperformanceimprovementprogrammayreducemortalityinseveresepsis(level2
[midlevel]evidence)
basedonbeforeandafterstudy
15,022patientswithseveresepsisorsepticshockat165institutionsinEurope,SouthAmerica,andUnitedStateswere
analyzedover39monthperiodduringprogramimplementation
improvementprogrambasedonSocietyofCriticalCareMedicine(SCCM)SurvivingSepsisCampaignguidelinesandincluded
initialcarebundle(first6hoursafterpresentation)
serumlactatemeasured
bloodculturesobtainedpriortoantibioticadministration
broadspectrumantibioticsadministeredwithin3hoursforemergencydepartmentadmissionsand1hourforintensive
careunitadmissions
ifhypotensiondevelopsand/orlactate>4mmol/L(36mg/dL)
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deliverinitialminimumof20mL/kgofcrystalloid(orcolloidequivalent)
applyvasopressorsforhypotensionnotrespondingtoinitialfluidresuscitationtomaintainmeanarterialpressure>65
mmHg
ifpersistenthypotensiondespitefluidresuscitation(septicshock)and/orlactate>4mmol/L(36mg/dL)
achievecentralvenouspressure>8mmHg
achievecentralvenousoxygensaturation>70%
managementbundle(first24hoursafterpresentation)
lowdosesteroidsadministeredforsepticshock
drotrecoginalfa(activatedproteinC)administeredforsepsisinducedorgandysfunction
glucosecontrolmaintained>lowerlimitofnormal<150mg/L(8.3mmol/L)
inspiratoryplateaupressuresmaintained<30cmH2Oformechanicallyventilatedpatients
comparingfirstquarterofimplementationvs.2yearsofimplementation
compliancewithinitialcarebundle10.9%vs.31.3%(p<0.0001)
compliancewithmanagementbundle18.4%vs.36.1%(p=0.008)
mortality37%vs.30.8%(p=0.001,NNT17)
inadjustedanalysis,improvementprogramassociatedwithabsolute5.4%(95%CI2.5%8.4%)decreaseinmortalityoverfirst
2yearsofimplementation
specifictargetsassociatedwithreducedhospitalmortalityafteradjustmentforbaselinecharacteristics
administrationofbroadspectrumantibiotics
obtainingbloodculturesbeforeantibiotics
maintainingbloodglucosecontrol
drotrecoginalfa(activatedproteinC)infirst24hoursamongpatientswithshock
achievingplateaupressurecontrol(<30cmH2O)amongpatientsneedingmechanicalventilation
ReferenceIntensiveCareMed2010Feb36(2):222fulltext,editorialcanbefoundinIntensiveCareMed2010Feb36(2):187
DynaMedcommentary drotrecoginalfa(activatedproteinC)(Xigris)hasbeenWITHDRAWNfromallmarketsduetofailureto
showsurvivalbenefitforpatientswithseveresepsisandsepticshock(FDAMedWatch2011Oct25)
hospitalvolumenotassociatedwithinhospitalmortalityorseverityofillnessinadultswithseveresepsisadmitted
tocriticalcareunitsinUnitedKingdom(level2[midlevel]evidence)
basedonretrospectivecohortstudy
30,727adultswithseveresepsisadmittedto170criticalcareunitsinUnitedKingdomduring20082009analyzed
noassociationfoundbetweenhospitalvolumeandinhospitalmortality,acuteseverityofillness,orreceiptofmechanical
ventilation
ReferenceBMJ2012May29344:e3394fulltext,editorialcanbefoundinBMJ2012May29344:e3494
GuidelinesandResources

Guidelines:
Internationalguidelines:
InternationalSurvivingSepsisCampaignguidelineonmanagementofsepsisandsepticshockcanbefoundinIntensiveCareMed
2017Mar43(3):304,commentarycanbefoundinJAMA2017Feb28317(8):807
SocietyofCriticalCareMedicineandtheEuropeanSocietyofIntensiveCareMedicinethirdinternationalconsensusdefinitionsfor
sepsisandsepticshock(Sepsis3)canbefoundinJAMA2016Feb23315(8):801fulltext,commentarycanbefoundinJAMA
2016Jul26316(4):456
DepartmentofHealthofIreland(AnRoinnSlinte)nationalclinicaleffectivenessguidelineonsepsismanagementcanbefoundat
AnRoinnSlinte2015MayPDF,accreditedbyUnitedKingdomNationalInstituteforHealthandCareExcellence
consensusrecommendationsfromAustraliaonnursingmeasuresinsepsisandsepticshockwithcommentaryfromGerman
perspectivecanbefoundinKinderkrankenschwester2012Oct31(10):422[German]
UnitedStatesguidelines:
AmericanSocietyforMicrobiology(ASM)/CentersforDiseaseControlandPrevention(CDC)LaboratoryMedicineBestPractices
(LMBP)guidelineoneffectivenessofpracticestoincreasetimelinessofprovidingtargetedtherapyforinpatientswithbloodstream
infectionscanbefoundinClinMicrobiolRev2016Jan29(1):59fulltextoratNationalGuidelineClearinghouse2017Mar13:50486
SocietyofCriticalCareMedicine(SCCM)practiceparametersonhemodynamicsupportofsepsisinadultpatientscanbefoundin
CritCareMed2004Sep32(9):1928
AmericanThoracicSociety/InfectiousDiseasesSocietyofAmerica(ATS/IDSA)guidelinesonthemanagementofadultswith
hospitalacquired,ventilatorassociated,andhealthcareassociatedpneumoniacanbefoundinAmJRespirCritCareMed2005
Feb15171(4):388
EasternAssociationforSurgeryofTrauma/SocietyofCriticalCareMedicine(EAST/SCCM)clinicalpracticeguidelineonredblood
celltransfusioninadulttraumaandcriticalcarecanbefoundinCritCareMed2009Dec37(12):3124PDF,correctioncanbe
foundinCritCareMed2010Jul38(7):1621,commentarycanbefoundinCritCareMed2010Aug38(8):1755
AmericanCollegeofEndocrinology/AmericanDiabetesAssociation(ACE/ADA)consensusstatementoninpatientdiabetesand
glycemiccontrolcanbefoundinEndocrPract2006JulAug12(4):458
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6/4/2017 DynaMed

AbingtonMemorialHospital(AMH)guidelineonsepsisforemergencytraumacentercanbefoundinHealthcareBenchmarksQual
Improv2011Mar18(3):27
UnitedKingdomguidelines:
NationalInstituteforHealthCareExcellence(NICE)guidanceonsepsis:recognition,diagnosisandearlymanagementcanbe
foundatNICE2016Jul:NG51PDForatNationalGuidelineClearinghouse2017Jan9:50412
RoyalCollegeofGynecologists(RCOG)guidelineonbacterialsepsisinpregnancycanbefoundatRCOG2012AprPDForat
NationalGuidelineClearinghouse2012Oct29:36901
RCOGguidelineonbacterialsepsisfollowingpregnancycanbefoundatRCOG2012AprPDForatNationalGuideline
Clearinghouse2012Oct29:36902
Canadianguidelines:
VentilatorAssociatedPneumonia(VAP)GuidelinesCommitteeandCanadianCriticalCareTrialsGroupcomprehensiveevidence
basedclinicalpracticeguidelineonventilatorassociatedpneumoniadiagnosisandtreatmentcanbefoundinJCritCare2008
Mar23(1):138
Europeanguidelines:
GermanSepsisSociety/GermanInterdisciplinaryAssociationforIntensiveandEmergencyCareMedicine(DSG/DIVI)guidelineon
prevention,diagnosis,treatment,andfollowupcareofsepsiscanbefoundinAnaesthesist2010Apr59(4):347,GerMedSci2010
Jun288:Doc14fulltext,orinInternist(Berl)2010Jul51(7):925[German]
Asianguidelines:
JapaneseSocietyofChemotherapyCommittee/JapaneseAssociationforAnaerobicInfectionResearchguidelineonanaerobic
infections(individualfields):bloodstreaminfectionswithanaerobicbacteriacanbefoundinJInfectChemother2011Jul17Suppl
1:47
Mexicanguidelines:
GruposdeDesarrollodelasInstitucionesPblicasdelSistemaNacionaldeSaluddeMxico(SecretaradeSalud,Instituto
MexicanodeSeguroSocia/InstitutodeSeguridadyServiciosSocialesparalosTrabajadoresdelEstado/SecretariadelaDefensa
Nacional/SecretariadeMarina/SistemaNacionalparaelDesarrolloIntegraldelaFamilia/PetroleosMexicano)
(IMSS/ISSSTE/SEDENA/SEMAR/DIF/PEMEX)guasdeprcticaclnicaendiagnsticoytratamientodesepsisgraveychoque
spticoeneladultosepuedenencontrarenSecretaradeSaludMxico2009PDF[Spanish]
CentralandSouthAmericanguidelines:
BrazilianAssociationofCriticalCareMedicine/BrazilianSocietyofInfectiousDiseases(AssociaodeMedicinaIntensiva
Brasileira/SociedadeBrasileiradeInfectologia[AMIB/SBI])guidelineonsepsis:hemodynamicresuscitationcanbefoundinRev
AssocMedBras2010SepOct56(5):497fulltext[Portuguese]
Reviewarticles:
reviewcanbefoundinBMJ2007Oct27335(7625):879fulltext
reviewcanbefoundinNEnglJMed2006Oct19355(16):1699,correctioncanbefoundinNEnglJMed2006Nov
23355(21):2267,commentarycanbefoundinNEnglJMed2007Mar15356(11):1179
reviewofsepsis:pathophysiologyandclinicalmanagementcanbefoundinBMJ2016May23353:i1585
reviewofidentifyingpatientswithsepsisinhospitalwardscanbefoundinChest2016Jun30earlyonline
reviewofadvancesindiagnosisandtreatmentofsepticshockcanbefoundinJAMA2015Aug18314(7):708,correctioncanbe
foundinJAMA2015Oct6314(13):1404
reviewofeffectofHIVinfectiononhostresponsetobacterialsepsiscanbefoundinLancetInfectDis2015Jan15(1):95
reviewofsepticshockcanbefoundinNEnglJMed2013Oct31369(18):1726
reviewofseveresepsisandsepticshockcanbefoundinNEnglJMed2013Aug29369(9):840,correctioncanbefoundinN
EnglJMed2013Nov21369(20):2069
reviewofcareofasplenicpatientcanbefoundinNEnglJMed2014Jul24371(4):349
reviewofpathogenesisofsepsiscanbefoundinAnnuRevPathol20116:19
reviewofbloodculturebaseddiagnosisofbacteremiacanbefoundinClinMicrobiolInfect2015Apr21(4):313
reviewofearlyrecognitionandmanagementofsepsisinadults:thefirstsixhourscanbefoundinAmFamPhysician2013Jul
188(1):44
reviewofseveresepsisandsepticshockinpregnancycanbefoundinObstetGynecol2012Sep120(3):689
reviewofhospitalacquiredinfectionsduetogramnegativebacteriacanbefoundinNEnglJMed2010May13362(19):1804
reviewofnormalmaternalphysiologicparametersinrelationshiptosystemicinflammatoryresponsesyndrome(SIRS)criteriacan
befoundinObstetGynecol2014Sep124(3):535
MEDLINEsearch:
tosearchMEDLINEfor(Sepsisinadults)withtargetedsearch(ClinicalQueries),clicktherapy,diagnosis,orprognosis
PatientInformation
handoutfromNationalInstituteofGeneralMedicalSciences
handoutfromKidsHealth

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handoutfromCentersforDiseaseControlandPreventionPDF
handoutfromClevelandClinic
handoutfromPatientUKPDF
technicalinformationfromPatientPlusPDF
handoutonbacteremiaandsepticshockfromTheMerckManualofMedicalInformationHomeEdition
ICD9/ICD10Codes
References

Generalreferencesused:
1.DellingerRP,LevyMM,RhodesA,etalSurvivingSepsisCampaignGuidelinesCommittee,PediatricSubgroup.SurvivingSepsis
Campaign:InternationalGuidelinesforManagementofSevereSepsisandSepticShock:2012.CritCareMed.2013Feb41(2):580
637,alsopublishedinIntensiveCareMed2013Feb39(2):165
2.LeverA,MackenzieI.Sepsis:definition,epidemiology,anddiagnosis.BMJ.2007Oct27335(7625):87983fulltext
3.MartinGS.Sepsis,severesepsisandsepticshock:changesinincidence,pathogensandoutcomes.ExpertRevAntiInfectTher.
2012Jun10(6):7016
4.SingerM,DeutschmanCS,SeymourCW,etalTheThirdInternationalConsensusDefinitionsforSepsisandSepticShock
(Sepsis3).JAMA.2016Feb23315(8):80110fulltext,commentarycanbefoundinJAMA2016Jul26316(4):456
5.RhodesA,EvansLE,AlhazzaniW,etalSurvivingSepsisCampaign:InternationalGuidelinesforManagementofSepsisand
SepticShock:2016.IntensiveCareMed2017Mar43(3):304
Recommendationgradingsystemsused:
SocietyofCriticalCareMedicine(SCCM)usesGradingofRecommendations,Assessment,Development,andEvaluation(GRADE)
strengthofrecommendation
Strongbenefitsclearlyoutweighrisksandburdens(orviceversa)formost,ifnotall,patients
Weakbenefitsandriskscloselybalancedand/oruncertain
BestpracticestatementrecommendationnotconducivetoGRADEprocess
qualityofevidence
Highrandomizedtrialswithoutfactorsthatreducequalityofevidence,orwelldoneobservationalstudieswithverylarge
magnitudeofeffect
Moderatedowngradedrandomizedtrialsorupgradedobservationalstudies
Lowwelldoneobservationalstudies,orrandomizedtrialswithmanylimitations
Verylowcaseseriesorexpertopinion
ReferenceSCCMSurvivingSepsisCampaign2016internationalguidelineonmanagementofseveresepsisandsepticshock
(IntensiveCareMed2017Mar43(3):304)
DynaMededitorialprocess:
DynaMedtopicsarecreatedandmaintainedbytheDynaMedEditorialTeamandProcess.
Alleditorialteammembersandreviewershavedeclaredthattheyhavenofinancialorothercompetinginterestsrelatedtothis
topic,unlessotherwiseindicated.
DynaMedprovidesPracticeChangingDynaMedUpdates,withsupportfromourpartners,McMasterUniversityandF1000.
Specialacknowledgements:
ParitoshPrasad,MD(AssistantProfessorofPulmonaryDiseasesandCriticalCare,UniversityofRochesterSchoolofMedicine
NewYork,UnitedStates)
AllenShaughnessy,PharmD,MMedEd,FCCP(ProfessorofFamilyMedicineandDirectorofMasterTeacherFellowship,Tufts
UniversityFamilyMedicineResidencyCambridgeHealthAllianceMassachusetts,UnitedStates)
AlanEhrlich,MD(ExecutiveEditorClinicalAssociateProfessorofFamilyMedicine,UniversityofMassachusettsMedicalSchool
Massachusetts,UnitedStates)
EditorialTeamroledefinitions
TopicEditorsdefinethescopeandfocusofeachtopicbyformulatingasetofclinicalquestionsandsuggestingimportant
guidelines,clinicaltrials,andotherdatatobeaddressedwithineachtopic.TopicEditorsalsoserveasconsultantsforthe
internalDynaMedPlusEditorialTeamduringthewritingandeditingprocess,andreviewthefinaltopicdraftspriortopublication.

SectionEditorshavesimilarresponsibilitiestoTopicEditorsbuthaveabroaderrolethatincludesthereviewofmultipletopics,
oversightofTopicEditors,andsystematicsurveillanceofthemedicalliterature.

RecommendationsEditorsprovideexplicitreviewofDynaMedPlusOverviewandRecommendationssectionstoensurethatall
recommendationsaresound,supported,andevidencebased.Thisprocessisdescribedin"SynthesizedRecommendation
Grading."

DeputyEditorsareemployeesofDynaMedandoverseeDynaMedPlusinternalpublishinggroups.Eachisresponsibleforall
contentpublishedwithinthatgroup,includingsupervisingtopicdevelopmentatallstagesofthewritingandeditingprocess,final
reviewofalltopicspriortopublication,anddirectionofaninternalteam.

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Mar29,citedplaceciteddatehere][about25screens].Availablefromhttp://search.ebscohost.com/login.aspx?
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