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    SIRS, SEPSIS, AN DM O D S

    Amjad Bani Hani

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    Objectives

    To know defnitions o SIRS, sepsis,septic shock, MODS

    To become amilia with theepidemiolo!" o sepsis

    To lean basic pathoph"siolo!"#in$ammation, cadio%asc&laph"siolo!"' o SIRS and sepsis

    B&t frst, a eal case(

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    Case presentation

    )*+"ea+old male

    l&+like s"mptoms o -da"

    In .R Temp */01 2&lse -*3 Blood pess&e 435*3 Respiations *6 2etechial ash 7hest, 78, Abdominal

    e9am nomal

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    Case presentation - 2

    :aboato" pH 406/, 2aO6 ;6,

    2a7O6 6/

    In%esti!ations pendin!

    Blood, &ine c&lt&es Oall" int&bated and

    placed on mechanical%entilation

    7ental %eno&scathete inseted 7eota9ime 6 ! i%

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    Case presentation - 3

    In I7=(

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    Case Presentation - 4

    .al" !am stain on blood e%ealed!am ne!ati%e ods

    2atient stated on( H"docotisone -33 m! i% >;h Recombinant acti%ated potein 7

    6)!5k!5ho& o /? ho&s

    .nteal n&tition %ia nasojej&nal eedin!t&be

    2oph"la9is o stess &lces, deep%eno&s thomboses

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    Case Presentation - Resolution

    2atient !ad&all" stabili@ed and impo%ed withcomplete esol&tion o o!an d"s&nction o%e 1 da"s

    inal c&lt&es confmed dia!nosis asmenin!ococcemia

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    Infection: Part of a biggerpicture

    Inection( 2esence o o!anisms in a

    closed space o locationwhee not nomall" o&nd

    Adapted om( Bone R7 et al0 Chest.-//6-3-(-?))+110Opal SM et al0 Crit Care Med0 63336;(S;-+60

    Inection

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    SIRS: System ic Inflam m atory ResponseSynrom e

    SIRS( A clinicalesponse aisin! om anonspecifc ins&ltmaniested b"

    6 o the ollowin!( Tempeat&e*;7 o *?7

    HR /3 beats5min

    Respiations 635min CB7 co&nt-6,3335m: o),3335m: o -3Eimmat&e ne&tophils

    Adapted om( Bone R7 et al0 Chest.-//6-3-(-?))+110Opal SM et al0 Crit Care Med0 63336;(S;-+60

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    Sepsis: ! ore "#an $ust Inflam m ation

    Sepsis( Fnown o s&spected

    inection SIRS citeia

    Adapted om( Bone R7 et al0 Chest.-//6-3-(-?))+110

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    Severe Sepsis: %cute Organ&ysfunction

    Se%ee Sepsis GSepsis with si!ns oacuteo!and"s&nction in an" o

    the ollowin! s"stems( 7adio%asc&la #septicshock'

    Renal Respiato"

    Hepatic Hemostasis 7

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    Sepsis: % Com ple' &isease

    Adapted om( Bone R7 et al0 Chest.-//6-3-(-?))+110

    Opal SM et al0 Crit Care Med0 63336;(S;-+60

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    $argon 2((2: PIRO

    InectionIn$ammation

    2h"siolo!icBiochemical

    SevereSepsis

    Specifc O!anSe%eit"

    Predisposition

    Insult Response

    Organ Dysfunction

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    Preisposition

    2e+e9istin! disease 7adiac, 2&lmona", Renal HI8

    A!e #e9temes o a!e'

    ende #males'

    enetics T

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    Response

    2h"siolo!" Heat ate Respiation

    e%e Blood pess&e 7adiac o&tp&t CB7

    H"pe!l"cemia

    Makes oIn$ammation T

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    Organ &ysfunction

    Lungs

    Kidneys

    CVS

    CNS

    PNS

    Coagulation

    GI

    Liver

    Endocrine

    Skeletal Muscle

    Adult es!iratory "istress Syndro#e

    Acute $u%ular Necrosis

    S&ock

    Meta%olic ence!&alo!at&y

    Critical Illness Polyneuro!at&y

    "isse#inated Intravascular

    Coagulo!at&y

    Gastro!aresis and ileus

    C&olestasis

    Adrenal insu''iciency

    &a%do#yolysis

    Specifc therapyexists

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    ! agnitue of t#e Problem

    .stimated 6-1,333 deaths om =S-//1 data

    Hi!h cost o mana!ement #I7= cae,dia!nostic testin!, d&!s' .stimated 63 da" :OS 66,333 cost

    Repesents /0*E o all deaths

    .>&als deaths ate ac&te m"ocadialinaction

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    "#e Incience of Sepsis in t#e

    )nite States

    The incidence o sepsis has

    inceased /-0* pecent o%e thelast ten "eas0

    This "ea, se%ee sepsis will likel"

    take 6-1,333 li%es0

    Sepsis is the leadin! ca&se odeath in the non+coona" I7=0

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    Se%ee sepsis takes moe li%esthan beast, colon5ectal,panceatic, and postate cance

    combined0

    One o e%e" thee patients who

    de%elop se%ee sepsiswill die within a month0

    So&ce( Societ" o 7itical 7ae

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    Severe Sepsis is deadly

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    Severe Sepsis is Com m on

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    Severe Sepsis is increasing

    in incidence

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    Sepsis: &efining a &isease Continuum

    A clinical esponseaisin!om a nonspecifcins&lt, incl&din! 6 othe ollowin!( Tempeat&e J*;o7 o

    K*?o7 HR J/3 beats5min Respiations J635min CB7 co&nt

    J-6,3335mm*oK),3335mm*o-3E immat&e

    ne&tophils

    SIRS G s"stemic in$ammato" esponses"ndome0

    Bone et al0 Chest.-//6-3-(-?))0

    SIRS with a pes&med oconfmed inectio&spocess

    SepsisSIRSInection5Ta&ma SevereSepsis

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    Sepsis: &efining a &isease Continuum

    Bone et al0 Chest.-//6-3-(-?)) Cheele and Benad0 N Engl J Med0 -///*)3(6340

    SepsisSIRSInection5Ta&ma SevereSepsis

    Sepsis with J- si!n o o!anail&e 7adio%asc&la #eacto"

    h"potension' Renal Respiato" Hepatic Hematolo!ic 7

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    *piem iology of Sepsis"#e International Co#ort Stuy

    SepsisInection

    SevereSepsis

    SepticShock

    -; 6; 6) *3

    *1E motalit"

    8353 patients with LOS > 24h

    4277 infections (2696 on admission)

    Percent of cases within each cateor!

    Albeti, Int 7ae Med 6336

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    Causes of Sepsis

    Bacteial inections aethe most common ca&seo sepsis, b&t sepsis canalso be ca&sed b" &n!al,paasitic, o %ialinections0

    The inection can

    oi!inate om an"wheein the bod"0

    So&ce:www.clevelandclinic.org

    http://www.clevelandclinic.org/http://www.clevelandclinic.org/
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    Sources of Sepsis"#e International Co#ort Stuy

    SevereSepsis

    SepticShock

    Respiato" ?? 1*Abdomen / 63

    Bacteemia -) -?

    =ina" -- --

    M&ltiple + +

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    ! icrobiology of Sepsis"#e International Co#ort Stuy

    SevereSepsis

    SepticShock

    am+positi%e )) )3

    am+ne!ati%e )4 )4

    &n!al / -*

    2ol"micobial + +

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    Inade>&ate

    Res&scitation

    Pat#ogenesis of SIRS+! O&S

    2eopeati%e Illness

    Ta&ma oOpeation

    Tiss&e Inj&"

    optimal o9"!endeli%e" and

    s&ppot

    Reco%e"

    ExcessiveInammatory

    Response

    SIRS5MODS

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    Initiation of Inflam m atory Response

    om Cheele L Benad,

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    M ediators of Septic

    Response

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    Pro-inflam m atory

    M ediatorsBacterial EndotoxinTNF-Interlekin-!Interlekin-"Interlekin-#$latelet %ctivatin& Factor '$%F(

    Inter)eron-*amma$rosta&landins+ekotrienes

    Nitric ,xide

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    Anti-inflam m atory

    M ediators Interlekin-!$*E.

    $rotein /Interlekin-"Interlekin-0Interlekin-!.

    +ipoxins*1-/SF

    T*F

    I+-!R%

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    Pat#op#ysiology of Sepsis

    Sepsis can lead to widespeadin$ammation and blood clottin!0

    Blood clottin! d&in! sepsis ca&sesed&ced blood $ow to limbs and

    %ital o!ans, and can lead to o!anail&e o tiss&e dama!e0So&ce( 7itical 7ae

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    Pat#op#ysiology of Sepsis

    In simple temssepsiscan be %iewedas an imbalance o

    in$ammation,coa!&lation, andfbinol"sis.

    In nomal patientshomeostasis ismaintained whenthese ae balanced.

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    Pat#op#ysiology of Sepsis

    D&in! a nomal esponse to bacteia inthe blood the imm&ne s"stem eleasesin$ammato" mediatos to pomoteeco%e" o the tiss&e0

    These mediatos ae known as( T&mo

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    Pat#op#ysiology of Sepsis

    The elease o the in$ammato"mediatos stats the 7oa!&lation 7ascadeleadin! to the de%elopment o a clot0

    To maintain this clot, inhibitos aeeleased

    to s&ppess fbinol"sis o beakdown0This is necessa" to ha%e time o the

    bod" to desto" the bacteia beoe theclot is !one0

    So&ce( 7itical 7ae

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    Pat#op#ysiology of Sepsis

    Once the bacteia oanti!en is isolated,the po+in$ammato"mediatos attactne&tophils o CB7swhich attack theanti!en and t" to

    en!&l it.

    aphics( Deloes Nittel, 633?

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    Pat#op#ysiology of Sepsis

    To pe%ent the esponse omdama!in! nomal tiss&e, anti+in$ammato"mediatos ae eleased

    incl&din! tansomin! !owth actosand intele&kins #I:+)'0 This balance oin$ammato" and anti+in$ammato"mediatos esticts the in$ammation

    esponse to the local site o inection.

    So&ce( 7itical 7ae

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    Pat#op#ysiology of Sepsis

    Chen the bod" is &nable to maintainthe appopiate balance, the imm&neesponse is no lon!e local b&tbecomes s"stemic0

    In$ammation and alteed clottin!>&ickl" spead tho&!h the bod"0

    So&ce( 7itical 7ae

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    Pat#op#ysiology of Sepsis

    The peson withthe inection

    which was oncelocali@ed co&ldbecome citicall"ill i this pocess is

    not coected.

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    ,om eostasis Is )nbalance inSevere Sepsis

    7a%alho A7, eeman

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    Coagulation an ibrinolysis

    "ernard# $%& '* 2++,-344-,+.699/7+9

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    .et/s .oo0 a .ittle &eeper

    Thee ae * inte!ated esponses to sepsis

    Acti%ation o In$ammation

    Acti%ation o 7oa!&lation

    Impaiment o ibinol"sis

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    %ctivation of Inflam m ation

    In$ammation is the bod"Ps esponse toinection.

    Chen this occ&s white blood cells #CB7s'!eneate and elease c"tokines omediatos o in$ammation.

    In$ammato" mediatos incl&de( T&monecosis acto+a, Intele&kin+-#I:+-',Intele&kin+? #I:+?' and 2latelet acti%atin!acto.

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    %ctivation of Inflam m ation

    Altho&!h these c"tokines #T

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    %ctivation of Inflam m ation

    Thee is basicall" a t&!o wa !oin! on betweenthe po+in$ammato"and anti+ in$ammato"components o the bod"0

    In sepsis, contin&edelease o po+

    in$ammato" c"tokineso%ewhelms the anti+in$ammato" c"tokines0

    2o+in$ammato" #I:+-,I:+?,T

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    %ctivation of Coagulation

    In$ammation and coa!&lation aeclosel" linked0 The c"tokines omin$ammation stim&late coa!&lationpathwa"s0 This es&lts in the omin! othe en@"me thombin0

    This pod&ces clottin! in the bod"0

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    %ctivation of Coagulation

    The enhancedclottin! contin&esmakin! tin" clots o

    micothombi inthe %asc&la s"stemwhich impais blood$ow and o!an

    pe&sion.

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    %ctivation of ibrinolysis

    ibinol"sis, o the beakdown o clots, isthe bod"Ps esponse to the inceasedclottin! and in$ammation0

    In sepsis this beakdown is inhibited oslowed beca&se o mediatos0 Thesemediatos ae called(

    2lasmino!en Acti%ato Inhibito+- #2AI+-'

    Thombin Acti%atable ibinol"sisInhibito #TAI'

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    %ctivation of ibrinolysis

    The incease le%els o these twoinhibitos,

    2lasmino!en Acti%ato Inhibito+-#2AI+-' and Thombin Acti%atableibinol"sis Inhibito #TAI', s&ppessfbinol"sis e%en moe ceatin! astate o coa!&lopath"0

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    aphics( Deloes Nittel, 633?

    The In$ammato", 7oa!&lation,and ibol"tic Response to

    Inection

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    ! a0ing ! atters 1 orse"#e Role of *not#elium in

    Sepsis

    aphic( Deloes Nittel, 633?

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    ! a0ing ! atters 1 orse"#e Role of *not#elium in

    Sepsis

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    ! a0ing ! atters 1 orse

    In sepsis the endotheli&m becomesdama!ed which makes thein$ammato" pocess wose b"

    eleasin! moe c"tokines #T

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    &am age *not#elium

    aphics( Deloes Nittel,633?

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    Putting it all "oget#er

    The imbalance

    o In$ammation,7oa!&lation, and

    ibinol"sis and theeQects on endotheli&mcan lead to o!anail&e e%en death ilet &ndetected o&nteated0

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    Inade2ate

    Resscitation

    Pat#ogenesis of SIRS+! O&S

    2eopeati%e Illness

    Ta&ma oOpeation

    Tiss&e Inj&"

    optimal o9"!endeli%e" and

    s&ppot

    Reco%e"

    .9cessi%eIn$ammato"

    Response

    SIRS5MODS

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    UO6 G low V O6

    content

    B2G7O V S8R

    Intra ,r&an 3istri4tion

    re&ional distri4tion

    1icrocirclation

    /ardiac,tpt

    Intra ,r&an 3istri4tion

    re&ional distri4tion

    1icrocirclation

    Regulation of o'ygen elivery

    /ardiacotpt

    'orma0 1norma0

    O'ygen &elivery

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    O'ygen &elivery

    Deli%e"(Demand mismatch

    DiQ&sion limitation #edema'

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    O'ygen Consum ption

    NADH+H+

    NAD+ADP + P

    i

    1/2 O2+H+

    ATP

    H+ Cytc

    H2O

    H+

    H+

    H+ H+

    Q

    2"&%ate Deh"do!enase #2DH' acti%it" deceased

    Deceased deli%e" o Acet"l 7oA to T7A c"cle

    Mitochondial d"s&nction

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    !estion" # $y do SepticPatients D ie?

    %ns5er6 ,r&anFailre

    i

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    O rgan %ail!re andM ortality

    7nas8 et al9 '!:#"(6

    3irect correlation 4et5een nm4er o) or&ansystems )ailed and mortality9

    1ortality 3ata6

    1 22% 31% 34% 35% 40% 42% 41%2 52% 67% 66% 62% 56% 64% 68%

    3 80% 95% 93% 96% 100%

    100%

    100%

    ;,SF 3! 3. 3< 30 3= 3" 3>

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    Evidence-&ased Sepsis

    ' !idelines/omponents6 Early Reco&nition

    Early *oal-3irected Therapy

    1onitorin& Resscitation

    $ressor ? Inotropic Spport

    Steroid Replacement

    Recom4inant %ctivated $rotein /

    Sorce /ontrol *lycemic /ontrol

    Ntritional Spport

    %d@ncts6 Stress Alcer $rophylaxis8 3T$rophylaxis8 Trans)sion8 Sedation8

    %nal&esia8 ,r&an Replacement

    Evidence-&ased Sepsis

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    Evidence &ased Sepsis' !idelines

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    Severe Sepsis:"#e inal Com m on Pat# ay

    Endothelial Dysunction andMicrovascular Thrombosis

    Hypoperusion/Ischemia

    Acute Organ Dysunction

    !evere !epsis"

    Death

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    Severe Sepsis:! anagem ent of Our Case

    Endothelial Dysunction andMicrovascular Thrombosis

    Hypoperusion/Ischemia

    Acute Organ Dysunction

    !evere !epsis"

    Death

    rhA#$$orticosteroids

    %luids&asopressors

    $&&H%

    Enteralnutrition

    !urvival