5/3/2017 Systemic Inammatory Response Syndrome: Background, P

Thissiteisintendedforhealthcareprofessionals

SystemicInflammatory
ResponseSyndrome
Updated:Aug16,2016
Author:LewisJKaplan,MD,FACS,FCCM,FCCP
ChiefEditor:MichaelRPinsky,MD,CM,Dr(HC),
FCCP,MCCMmore...

OVERVIEW

Background
In1992,theAmericanCollegeofChestPhysicians
(ACCP)andtheSocietyofCriticalCareMedicine
(SCCM)introduceddefinitionsforsystemic
inflammatoryresponsesyndrome(SIRS),sepsis,
severesepsis,septicshock,andmultipleorgan
dysfunctionsyndrome(MODS).[1]Theideabehind
definingSIRSwastodefineaclinicalresponsetoa
nonspecificinsultofeitherinfectiousor
noninfectiousorigin.SIRSisdefinedas2ormoreof
thefollowingvariables(seePresentationand
Workup):

Feverofmorethan38C(100.4F)orless
than36C(96.8F)

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Heartrateofmorethan90beatsperminute
Respiratoryrateofmorethan20breathsper
minuteorarterialcarbondioxidetension
(PaCO2)oflessthan32mmHg
Abnormalwhitebloodcellcount(>12,000/L
or<4,000/Lor>10%immature[band]forms)

SIRSisnonspecificandcanbecausedbyischemia,
inflammation,trauma,infection,orseveralinsults
combined.Thus,SIRSisnotalwaysrelatedto
infection.(SeePathophysiologyandEtiology.)

Venndiagramshowingoverlapofinfection,bacteremia,
sepsis,systemicinflammatoryresponsesyndrome
(SIRS),andmultiorgandysfunction.

Bacteremia,sepsis,andsepticshock

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Infectionisdefinedas"amicrobialphenomenon
characterizedbyaninflammatoryresponsetothe
microorganismsortheinvasionofnormallysterile
tissuebythoseorganisms."

Bacteremiaisthepresenceofbacteriawithinthe
bloodstream,butthisconditiondoesnotalwayslead
toSIRSorsepsis.Sepsisisthesystemicresponse
toinfectionandisdefinedasthepresenceofSIRS
inadditiontoadocumentedorpresumedinfection.
Severesepsismeetstheaforementionedcriteria
andisassociatedwithorgandysfunction,
hypoperfusion,orhypotension.(SeeEtiology,
Treatment,andMedication.)

Sepsisinducedhypotensionisdefinedas"the
presenceofasystolicbloodpressureoflessthan
90mmHgorareductionofmorethan40mmHg
frombaselineintheabsenceofothercausesof
hypotension."Patientsmeetthecriteriaforseptic
shockiftheyhavepersistenthypotensionand
perfusionabnormalitiesdespiteadequatefluid
resuscitation.MODSisastateofphysiologic
derangementsinwhichorganfunctionisnot
capableofmaintaininghomeostasis.(See
Pathophysiology.)

Althoughnotuniversallyacceptedterminology,
severeSIRSandSIRSshockaretermsthatsome
authorshaveproposed.Thesetermssuggestorgan
dysfunctionorrefractoryhypotensionrelatedtoan
ischemicorinflammatoryprocessratherthantoan
infectiousetiology.

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Complications

Complicationsvarybasedonunderlyingetiology.
Routineprophylaxis,includingdeepveinthrombosis
(DVT)andstressulcerprophylaxis,shouldbe
initiatedwhenclinicallyindicatedinseverelyillbed
riddenpatients,especiallyiftheyrequiremechanical
ventilation.Longtermantibiotics,whenclinically
indicated,shouldbeasnarrowspectrumaspossible
tolimitthepotentialforsuperinfection(suggestedby
anewfever,achangeinthewhitebloodcell[WBC]
count,orclinicaldeterioration).Unnecessary
vascularcathetersandFoleycathetersshouldbe
removedassoonaspossible.(SeePrognosis,
Treatment,andMedication.)

Potentialcomplicationsincludethefollowing:

Respiratoryfailure,acuterespiratorydistress
syndrome(ARDS),andnosocomial
pneumonia
Renalfailure
Gastrointestinal(GI)bleedingandstress
gastritis
Anemia
DVT
Intravenouscatheterrelatedbacteremia
Electrolyteabnormalities
Hyperglycemia
Disseminatedintravascularcoagulation(DIC)

Patienteducation

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Educationshouldideallytargetthepatient'sfamily.
Familymembersneedtounderstandthefluidnature
ofimmuneresponsivenessandthatSIRSisa
potentialharbingerofothermorediresyndromes.

Pathophysiology
Systemicinflammatoryresponsesyndrome(SIRS),
independentoftheetiology,hasthesame
pathophysiologicproperties,withminordifferences
inincitingcascades.Manyconsiderthesyndromea
selfdefensemechanism.Inflammationisthebody's
responsetononspecificinsultsthatarisefrom
chemical,traumatic,orinfectiousstimuli.The
inflammatorycascadeisacomplexprocessthat
involveshumoralandcellularresponses,
complement,andcytokinecascades.Bone[1]best
summarizedtherelationshipbetweenthese
complexinteractionsandSIRSasthefollowing3
stageprocess.

StageI
Followinganinsult,cytokinesareproducedatthe
site.Localcytokineproductionincitesan
inflammatoryresponse,therebypromotingwound
repairandrecruitmentofthereticularendothelial
system.Thisprocessisessentialfornormalhost
defensehomeostasisandifabsentisnotcompatible
withlife.Localinflammation,suchasintheskinand
subcutaneoussofttissues,carriestheclassic
descriptionofrubor,tumor,dolor,calorandfunctio
laesa.

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Rubororrednessreflectslocalvasodilationcaused
byreleaseoflocalvasodilatingsubstanceslikenitric
oxide(NO)andprostacyclin.

Tumororswellingisduetovascularendothelialtight
junctiondisruptionandthelocalextravasationof
proteinrichfluidintotheinterstitium,whichalso
allowsactivatedwhitebloodcellstopassfromthe
vascularspaceintothetissuespacetohelpclear
infectionandpromoterepair.

Dolorispainandrepresentstheimpact
inflammatorymediatorshaveonlocal
somatosensorynerves.Presumably,thispainstops
thehostfromtryingtousethispartofhisorher
bodyasittriestorepairitself.

Caloristheincreasedheatprimarilydueto
increasedbloodflowbutalsoincreasedlocal
metabolismaswhitebloodcellsbecomeactivated
andlocalizetotheinjuredtissue.

Finally,functiolaesaislossoffunction,ahallmarkof
inflammationandacommonclinicalfindingoforgan
dysfunctionwiththeinfectionisisolatedtoaspecific
organ(eg,pneumoniaacuterespiratoryfailure
kidneyacutekidneyinjury).

Importantly,onalocallevel,thiscytokineand
chemokinereleasebyattractingactivated
leukocytestotheregionmaycauselocaltissue
destruction(eg,abscess)orcellularinjury(eg,pus),
whichappeartobethenecessarybyproductsofan
effectivelocalinflammatoryresponse.

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StageII

Smallquantitiesoflocalcytokinesarereleasedinto
thecirculation,improvingthelocalresponse.This
leadstogrowthfactorstimulationandthe
recruitmentofmacrophagesandplatelets.This
acutephaseresponseistypicallywellcontrolledby
adecreaseintheproinflammatorymediatorsandby
thereleaseofendogenousantagoniststhegoalis
homeostasis.Atthisstage,someminimalmalaise
andlowgradefevermaybecomemanifest.

StageIII

Ifhomeostasisisnotrestoredandifthe
inflammatorystimulicontinuetoseedintothe
systemiccirculation,asignificantsystemicreaction
occurs.Thecytokinereleaseleadstodestruction
ratherthanprotection.Aconsequenceofthisisthe
activationofnumeroushumoralcascadesandthe
activationofthereticularendothelialsystemand
subsequentlossofcirculatoryintegrity.Thisleadsto
endorgandysfunction.

Multihittheory

Bonealsoendorsedamultihittheorybehindthe
progressionofSIRStoorgandysfunctionand
possiblymultipleorgandysfunctionsyndrome
(MODS).Inthistheory,theeventthatinitiatesthe
SIRScascadeprimesthepump.Witheach
additionalevent,analteredorexaggerated
responseoccurs,leadingtoprogressiveillness.The

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keytopreventingthemultiplehitsisadequate
identificationofthecauseofSIRSandappropriate
resuscitationandtherapy.

Inflammatorycascade
Trauma,inflammation,orinfectionleadstothe
activationoftheinflammatorycascade.Initially,a
proinflammatoryactivationoccurs,butalmost
immediatelythereafterareactivesuppressinganti
inflammatoryresponseoccurs.ThisSIRSusually
manifestsitselfasincreasedsystemicexpressionof
bothproinflammatoryandantiinflammatoryspecies.
WhenSIRSismediatedbyaninfectiousinsult,the
inflammatorycascadeisofteninitiatedbyendotoxin
orexotoxin.Tissuemacrophages,monocytes,mast
cells,platelets,andendothelialcellsareableto
produceamultitudeofcytokines.Thecytokines
tissuenecrosisfactoralpha(TNF)and
interleukin1(IL1)arereleasedfirstandinitiate
severalcascades.

ThereleaseofIL1andTNF(orthepresenceof
endotoxinorexotoxin)leadstocleavageofthe
nuclearfactorkB(NFkB)inhibitor.Oncethe
inhibitorisremoved,NFkBisabletoinitiatethe
productionofmessengerribonucleicacid(mRNA),
whichinducestheproductionotherproinflammatory
cytokines.

IL6,IL8,andinterferongammaaretheprimary
proinflammatorymediatorsinducedbyNFkB.In
vitroresearchsuggeststhatglucocorticoidsmay
functionbyinhibitingNFkB.TNFandIL1have

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beenshowntobereleasedinlargequantitieswithin
1hourofaninsultandhavebothlocalandsystemic
effects.Invitrostudieshaveshownthatthese2
cytokinesgivenindividuallyproducenosignificant
hemodynamicresponsebutthattheycausesevere
lunginjuryandhypotensionwhengiventogether.
TNFandIL1areresponsibleforfeverandthe
releaseofstresshormones(norepinephrine,
vasopressin,activationofthereninangiotensin
aldosteronesystem).

Othercytokines,especiallyIL6,stimulatethe
releaseofacutephasereactantssuchasCreactive
protein(CRP)andprocalcitonin.Ofnote,infection
hasbeenshowntoinduceagreaterreleaseofTNF
thusinducingagreaterreleaseofIL6andIL8
thantraumadoes.Thisissuggestedtobethe
reasonhigherfeverisassociatedwithinfection
ratherthantrauma.

Theproinflammatoryinterleukinseitherfunction
directlyontissueorworkviasecondarymediatorsto
activatethecoagulationcascadeandthe
complementcascadeandthereleaseofnitricoxide,
plateletactivatingfactor,prostaglandins,and
leukotrienes.

Highmobilitygroupbox1(HMGB1)isaprotein
presentinthecytoplasmandnucleiinamajorityof
celltypes.Inresponsetoinfectionorinjury,asis
seenwithSIRS,HMGB1issecretedbyinnate
immunecellsand/orreleasedpassivelybydamaged
cells.Thus,elevatedserumandtissuelevelsof
HMGB1wouldresultfrommanyofthecausesof
SIRS.
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HMGB1actsasapotentproinflammatorycytokine
andisinvolvedindelayedendotoxinlethalityand
sepsis.[2]Inanobservationalstudyofpatientswith
traumaticbraininjury,multivariateanalysisselected
plasmaHMGB1levelasanindependentpredictor
for1yearmortalityandunfavorableoutcome.[3]
Therapeuticstudiesareunderwaytoevaluate
variousmechanismstoblockHMGB1,withhopesof
improvingoutcomesinSIRSandsepsissyndromes.
[2]

Numerousproinflammatorypolypeptidesarefound
withinthecomplementcascade.Protein
complementsC3aandC5ahavebeenthemost
studiedandarefelttocontributedirectlytothe
releaseofadditionalcytokinesandtocause
vasodilatationandincreasingvascularpermeability.
Prostaglandinsandleukotrienesinciteendothelial
damage,leadingtomultiorganfailure.

Polymorphonuclearcells(PMNs)fromcriticallyill
patientswithSIRShavebeenshowntobemore
resistanttoactivationthanPMNsfromhealthy
donors,but,whenstimulated,demonstratean
exaggeratedmicrobicidalresponse.Thismay
representanautoprotectivemechanisminwhichthe
PMNsinthealreadyinflamedhostmayavoid
excessiveinflammation,thusreducingtheriskof
furtherhostcellinjuryanddeath.[4]

Coagulation

Thecorrelationbetweeninflammationand
coagulationiscriticaltounderstandingthepotential

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progressionofSIRS.IL1andTNFdirectlyaffect
endothelialsurfaces,leadingtotheexpressionof
tissuefactor.Tissuefactorinitiatestheproductionof
thrombin,therebypromotingcoagulation,andisa
proinflammatorymediatoritself.Fibrinolysisis
impairedbyIL1andTNFviaproductionof
plasminogenactivatorinhibitor1.Proinflammatory
cytokinesalsodisruptthenaturallyoccurringanti
inflammatorymediatorsantithrombinandactivated
proteinC(APC).

Ifunchecked,thiscoagulationcascadeleadsto
complicationsofmicrovascularthrombosis,
includingorgandysfunction.Thecomplement
systemalsoplaysaroleinthecoagulationcascade.
Infectionrelatedprocoagulantactivityisgenerally
moreseverethanthatproducedbytrauma.

SIRSversusCARS

Thecumulativeeffectofthisinflammatorycascade
isanunbalancedstatewithinflammationand
coagulationdominating.Tocounteracttheacute
inflammatoryresponse,thebodyisequippedto
reversethisprocessviathecounterinflammatory
responsesyndrome(CARS).IL4andIL10are
cytokinesresponsiblefordecreasingtheproduction
ofTNF,IL1,IL6,andIL8.Infact,this
proinflammatoryandantiinflammatoryactivation
mirrorsotherhomeostaticprocesses,like
coagulation,anticoagulation,complementactivation,
andcomplementsuppression.

Clearly,thenormalhomeostaticprocessesattempt
tokeeptheseverytoxicinflammatoryprocessesin
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check.Inflammationisanessentialcomponentof
hostdefenseandservesaverystronglypositive
survivalfunctioninsuppressingandtheneliminating
localinfectionandtissueinjury.Itisonlywhenthis
localizedaggressiveinjuryprocessgainsaccessto
thewholebodythroughthebloodstreamand
lymphaticsthataSIRSdevelops.

Theacutephaseresponsealsoproduces
antagoniststoTNFandIL1receptors.These
antagonistseitherbindthecytokine,andthereby
inactivateit,orblockthereceptors.Comorbidities
andotherfactorscaninfluenceapatient'sabilityto
respondappropriately.

ThebalanceofSIRSandCARShelpsdeterminea
patient'soutcomeafteraninsult.Someresearchers
believethat,becauseofCARS,manyofthenew
medicationsmeanttoinhibittheproinflammatory
mediatorsmayleadtodeleterious
immunosuppression.

Etiology
Theetiologyofsystemicinflammatoryresponse
syndrome(SIRS)isbroadandincludesinfectious
andnoninfectiousconditions,surgicalprocedures,
trauma,medications,andtherapies.

Thefollowingispartiallistoftheinfectiouscausesof
SIRS:

Bacterialsepsis
Burnwoundinfections
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Candidiasis
Cellulitis
Cholecystitis
Communityacquiredpneumonia[5]
Diabeticfootinfection
Erysipelas
Infectiveendocarditis
Influenza
Intraabdominalinfections(eg,diverticulitis,
appendicitis)
Gasgangrene
Meningitis
Nosocomialpneumonia
Pseudomembranouscolitis
Pyelonephritis
Septicarthritis
Toxicshocksyndrome
Urinarytractinfections(maleandfemale)

Thefollowingisapartiallistofthenoninfectious
causesofSIRS:

Acutemesentericischemia
Adrenalinsufficiency
Autoimmunedisorders
Burns
Chemicalaspiration
Cirrhosis
Cutaneousvasculitis
Dehydration
Drugreaction
Electricalinjuries
Erythemamultiforme
Hemorrhagicshock

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Hematologicmalignancy
Intestinalperforation
Medicationsideeffect(eg,fromtheophylline)
Myocardialinfarction
Pancreatitis[6]
Seizure
SubstanceabuseStimulantssuchascocaine
andamphetamines
Surgicalprocedures
Toxicepidermalnecrolysis
Transfusionreactions
Uppergastrointestinalbleeding
Vasculitis

Epidemiology
OccurrenceintheUnitedStates
Thetrueincidenceofsystemicinflammatory
responsesyndrome(SIRS)isunknownbutprobably
veryhigh,owingtothenonspecificnatureofits
definition.NotallpatientswithSIRSrequire
hospitalizationorhavediseasesthatprogressto
seriousillness.Indeed,patientswithaseasonal
headcoldduetorhinovirususuallyfulfillthecriteria
forSIRS.BecauseSIRScriteriaarenonspecificand
occurinpatientswhopresentwithconditions
rangingfrominfluenzatocardiovascularcollapse
associatedwithseverepancreatitis,[6]anyincidence
figureswouldneedtobestratifiedbasedonSIRS
severity.

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RangelFaustoetalpublishedaprospectivesurvey
ofpatientsadmittedtoatertiarycarecenterthat
revealed68%ofhospitaladmissionstosurveyed
unitsmetSIRScriteria.[7]TheincidenceofSIRS
increasedasthelevelofunitacuityincreased.The
followingprogressionofpatientswithSIRSwas
noted:26%developedsepsis,18%developed
severesepsis,and4%developedsepticshock
within28daysofadmission.

PittetetalperformedahospitalsurveyofSIRSthat
revealedanoverallinhospitalincidenceof542
episodesper1000hospitaldays.[8]Incomparison,
theincidenceintheintensivecareunit(ICU)was
840episodesper1000hospitaldays.Itisnotclear
whatpercentageofpatientswithSIRShavea
primaryinfectiousetiology,allowingthemtobe
classifiedashavingsepsis.However,mostlikelythe
proportionofSIRSpatientsvariesacrosspatient
andhospitalgroups,beinghighestforexamplein
acutecaresettingsandinthosewithimmune
deficiency.

Theetiologyofpatientsadmittedwithseveresepsis
fromacommunityemergencydepartmentwas
evaluatedbyHeffneretal,whodeterminedthat
55%ofpatientshadnegativeculturesandthat18%
werediagnosedwithnoninfectiouscausesthat
mimickedsepsis(SIRS).Manyofthenoninfectious
etiologiesrequiredurgentalternatediseasespecific
therapy(eg,pulmonaryembolism,myocardial
infarction,pancreatitis).OftheSIRSpatientswithout
infection,theclinicalcharacteristicsweresimilarto
thosewithpositivecultures.[9]
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Anotherstudydemonstratedthat62%ofpatients
whopresentedtotheemergencydepartmentwith
SIRShadaconfirmedinfection,while38%didnot.
Withinthesamecohortofpatients,38%ofinfected
patientsdidnotpresentwithSIRS.[10]

Still,AngusetalfoundtheincidenceofsevereSIRS
associatedwithinfectiontobe3casesper1,000
population,or2.26casesper100hospital
discharges.[11]TherealincidenceofSIRS,
therefore,mustbemuchhigherandlikelydepends
somewhatontherigorwithwhichthedefinitionis
applied.

Internationaloccurrence
NodifferenceinthefrequencyofSIRSexistsbased
onworldgeography.

Sexrelateddemographics

ThesexbasedmortalityriskofsevereSIRSis
unknown.Femalestendtohavelessinflammation
fromthesamedegreeofproinflammatorystimuli
becauseofthemitigatingaspectsofestrogen.The
mortalityrateamongwomenwithseveresepsisis
similartothatofmenwhoare10yearsyounger
however,whetherthisprotectiveeffectappliesto
womenwithnoninfectiousSIRSisunknown.

Agerelateddemographics

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Extremesofage(youngandold)andconcomitant
comorbiditiesprobablynegativelyaffectthe
outcomeofSIRS.Youngpeoplemaybeableto
mountamoreexuberantinflammatoryresponsetoa
challengethanolderpeopleandyetmaybeableto
bettermodifytheinflammatorystate(viathe
counterinflammatoryresponsesyndrome[CARS]).
Youngpeoplehavebetteroutcomesforequivalent
diagnoses.

Prognosis
Comstedtetal,inastudyofsystemicinflammatory
responsesyndrome(SIRS)inacutelyhospitalized
medicalpatients,demonstrateda6.9timeshigher
28daymortalityinSIRSpatientsthaninnonSIRS
patients.MostdeathsoccurredinSIRSpatientswith
anassociatedmalignancy.[10]

PrognosisdependsontheetiologicsourceofSIRS,
aswellasonassociatedcomorbidities.The
mortalityratesinthepreviouslymentionedRangel
Faustoetalstudywere7%(SIRS),16%(sepsis),
20%(severesepsis),and46%(septicshock).[7]
ThemediantimeintervalfromSIRStosepsiswas
inverselyrelatedtothenumberofSIRScriteriamet.
MorbidityisrelatedtothecausesofSIRS,
complicationsoforganfailure,andthepotentialfor
prolongedhospitalization.

However,thelargeretrospectivestudyofallof
AustraliaandNewZealandICUcarefrom2000
2012demonstratedaclearprogressivedeclinein

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severesepsisandsepticshockmortalityfrom35%
to18%overthisperiod,withequaltrendsacrossall
agegroupsandtreatmentsettings.[12]Thesedata
suggestthatattentiontodetail,usingbestpractices
andoverallqualitycare,hasnearlyhalvedmortality
fromseveresepsisindependentofanyspecific
treatment.Thus,attentiontooverallpatientstatus
anduseofprovenriskreductionapproaches(eg,
stressulcerprophylaxis,DVTprophylaxis,daily
awakening,andweaningtrialsinventilator
dependentpatients)arecentraltoimproving
outcomefromseveresepsis.

Pittetetalshowedthatcontrolpatientshadthe
shortesthospitalstay,whilepatientswithSIRS,
sepsis,andseveresepsis,respectively,required
progressivelylongerhospitalstays.[8]

AstudybyShapiroetalevaluatedmortalityin
patientswithsuspectedinfectionintheemergency
departmentandfoundthefollowinginhospital
mortalityrates[13]:

SuspectedinfectionwithoutSIRS2.1%
Sepsis1.3%
Severesepsis9.2%
Septicshock28%

Inthestudy,thepresenceofSIRScriteriaalonehad
noprognosticvalueforeitherinhospitalmortalityor
1yearmortality.Eachadditionalorgandysfunction
increasedtheriskofmortalityat1year.Theauthors
concludedthatorgandysfunction,ratherthanSIRS
criteria,wasabetterpredictorofmortality.

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SinningetalevaluatedtheSIRScriteriainpatients
whounderwenttranscatheteraorticvalve
implantation(TAVI)andfoundthatSIRSappeared
tobeastrongpredictorofmortality.Theoccurrence
ofSIRSwascharacterizedbyasignificantly
elevatedreleaseofIL6andIL8,withsubsequent
increaseintheleukocytecount,Creactiveprotein
(CRP),andprocalcitonin.TheoccurrenceofSIRS
wasrelatedto30dayand1yearmortality(18%vs
1.1%and52.5%vs9.9%,respectively)and
independentlypredicted1yearmortalityrisk.[14]

IntheaforementionedHeffneretalstudy,patients
withoutanidentifiedinfectionhadalowerhospital
mortalityratethandidpatientswithaninfectious
etiologyfortheirSIRS(9%vs15%,respectively).[9]

ClinicalPresentation

References

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MediaGallery
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Venndiagramshowingoverlapofinfection,
bacteremia,sepsis,systemicinflammatory
responsesyndrome(SIRS),andmultiorgan
dysfunction.

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ContributorInformationandDisclosures

Author

LewisJKaplan,MD,FACS,FCCM,
FCCPAssociateProfessorofSurgery,Divisionof
Trauma,SurgicalCriticalCare,andEmergency
Surgery,PerelmanSchoolofMedicine,Universityof
PennsylvaniaSectionChief,SurgicalCriticalCare,
PhiladelphiaVeteransAffairsMedicalCenter

LewisJKaplan,MD,FACS,FCCM,FCCPisa
memberofthefollowingmedicalsocieties:
AmericanAssociationfortheSurgeryofTrauma,
AmericanCollegeofSurgeons,Associationfor
AcademicSurgery,AssociationforSurgical
Education,ConnecticutStateMedicalSociety,
EasternAssociationfortheSurgeryofTrauma,
InternationalTraumaAnesthesiaandCriticalCare

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5/3/2017 Systemic Inammatory Response Syndrome: Background, P
Society,SocietyfortheAdvancementofBlood
Management,SocietyofCriticalCareMedicine,
SurgicalInfectionSociety

Disclosure:Nothingtodisclose.

ChiefEditor

MichaelRPinsky,MD,CM,Dr(HC),FCCP,
MCCMProfessorofCriticalCareMedicine,
Bioengineering,CardiovascularDisease,Clinical
andTranslationalScienceandAnesthesiology,Vice
ChairofAcademicAffairs,DepartmentofCritical
CareMedicine,UniversityofPittsburghMedical
Center,UniversityofPittsburghSchoolofMedicine

MichaelRPinsky,MD,CM,Dr(HC),FCCP,MCCM
isamemberofthefollowingmedicalsocieties:
AmericanCollegeofChestPhysicians,American
CollegeofCriticalCareMedicine,American
ThoracicSociety,EuropeanSocietyofIntensive
CareMedicine,SocietyofCriticalCareMedicine

Disclosure:Receivedincomeinanamountequalto
orgreaterthan$250from:Masimo,Edwards
Lifesciences,CheetahMedical<br/>Received
honorariafromLiDCOLtdforconsultingReceived
intellectualpropertyrightsfromiNTELOMEDfor
boardmembershipReceivedhonorariafrom
EdwardsLifesciencesforconsultingReceived
honorariafromMasimo,Incforboardmembership.

Acknowledgements

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HeatherleeBailey,MDAssistantProgramDirector,
AssistantProfessor,DepartmentofEmergency
Medicine,DivisionofCriticalCare,MedicalCollege
ofPennsylvaniaHahnemannUniversity

HeatherleeBailey,MDisamemberofthefollowing
medicalsocieties:AmericanAcademyof
EmergencyMedicine,AssociationforSurgical
Education,SocietyforAcademicEmergency
Medicine,andSocietyofCriticalCareMedicine

Disclosure:Nothingtodisclose.

StevenDBurdette,MD,FIDSAAssociate
ProfessorofMedicine,ProgramDirector,Infectious
DiseasesFellowship,WrightStateUniversity,
BoonshoftSchoolofMedicineInfectiousDisease
AdvisortoTransplantProgram,MiamiValley
HospitalMedicalDirectorofInfectiousDiseases,
GreenMemorialHospital

StevenDBurdette,MD,FIDSAisamemberofthe
followingmedicalsocieties:AlphaOmegaAlpha,
AmericanSocietyforMicrobiology,American
SocietyofTransplantation,InfectiousDiseases
SocietyofAmerica,andTransplantationSociety

Disclosure:CubistHonorariaSpeakingand
teachingMerckHonorariaSpeakingandteaching

JosephFJohnJr,MD,FACP,FIDSA,FSHEA
ClinicalProfessorofMedicine,MolecularGenetics
andMicrobiology,MedicalUniversityofSouth
CarolinaCollegeofMedicineAssociateChiefof

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StaffforEducation,RalphHJohnsonVeterans
AffairsMedicalCenter

Disclosure:Nothingtodisclose.

KlausDieterLessnau,MD,FCCPClinical
AssociateProfessorofMedicine,NewYork
UniversitySchoolofMedicineMedicalDirector,
PulmonaryPhysiologyLaboratoryDirectorof
ResearchinPulmonaryMedicine,Departmentof
Medicine,SectionofPulmonaryMedicine,Lenox
HillHospital

KlausDieterLessnau,MD,FCCPisamemberof
thefollowingmedicalsocieties:AmericanCollegeof
ChestPhysicians,AmericanCollegeofPhysicians,
AmericanMedicalAssociation,AmericanThoracic
Society,andSocietyofCriticalCareMedicine

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MiguelAParilo,MD,FACPAssociateClinical
ProfessorofMedicine,DepartmentofMedicine,
WrightStateUniversity,BoonshoftSchoolof
MedicineMedicalDirector,TheBullFamily
DiabetesCenter

Disclosure:Nothingtodisclose.

FranciscoTalavera,PharmD,PhDAdjunct
AssistantProfessor,UniversityofNebraskaMedical
CenterCollegeofPharmacyEditorinChief,
MedscapeDrugReference

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