kuliah uniba 18-4-12 sepsis & septic shok fp940325-e

8/17/2019 Kuliah Uniba 18-4-12 Sepsis & Septic Shok FP940325-E

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SEPSIS

DR Putra Hendra SpPD

UNIBA


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• Hippocrates:

– Breakdown of liin! tissues: "pepsis# and "sepsis#

• $elsus:

– Ru%or & Perip'eral asodilatation – Dolor & Altered (ental status

– $alor & )eer* '+pot'er(ia

– ,u(or & -ede(a

• .alen: – )unctio laesa & -r!an d+sfunction

Definition – /000 +ears a!o


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)ro( %lood poisonin! to

sepsis• "Sepsis&s+ndro(e# :

• )eer or '+pot'er(ia 12 34 o$ or 5 36 o$7 • ,ac'+cardia 12809(in7

• eukoc+tosis or leukopenia 12 ;/ 000cells9((3* 5 N Engl J Med ;84?@ 3;?: 6<

• $onsensus conference A$$P9S$$:• Infection• Bacterae(ia• S+ste(ic infla((ator+ response s+ndro(e 1SIRS7• Sepsis C SIRS Infection

• Seere sepsis 1Sepsis one or!an d+sfunction7• Septic s'ock 1'+poperfusion despite adeuate fluid load7• ultiple S+ste( -r!an )ailure 1S-)7

A$$P9S$$> Crit Care Med ;88/@ /0: 46


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Seere Sepsis

• Sti(ulation of infla((ator+ cascades

• $ardioascular deran!e(ent

• Fasople!ia G '+potension

• Relatie '+poolae(ia• idespread d+sfunction of (icrocirculation: capillar+ leak

• Si(ultaneous actiation of coa!ulation cascades

• )or(ation of intraascular t'ro(%us

• ,issue inur+ G (ulti&or!an d+sfunction


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Septic ShockSIRS, plus evidence of Infection, plus organ

Failure, plus refractoryHypotension215,000 cases

Number of death/yr90,000

Mortality 45%

Number of death/yr

60,000Mortality 15%

Number of death/yr60,000

Mortality 20%

SystemicInflammatoryResponseSyndromeSIRS!

≥2 of the follo"ing#$ ≥ %&o' (r )%*o'+ulse ≥ 0 minRespirations ≥ 20min-hite cells .12000(r )/000 min or.10 and forms

S+SIS

SIRS, plus evidenceof Infection/00,000 cases

Severe SepsisSIRS, plus evidence

of Infection, plusorgan failure%00,000 cases


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Excessive inflammatory mediator production during sepsi

(Riedemann et al. Nat Med 2003;9:51

Pro-inflammatory cytokines +

chemokines

ROS production

Enzyme release

Vascular permeaility

!acterial killing

"#$

%achypnea&ever

'eukocytosis

%achycardia

Peripheral resistance

Edema

%issue damageOrgan failure

'eukocytopenia

Shutdo(n of neutrophil )

Phagocytic cell function

Susceptiility to infection*PERRE,$%#VE

#./E RESPO/SE*PORE,$%#VE

#./E RESPO/SE0

#./E P,R,'S#S

$OP'EE/% SS%E

$O,1.',%#O/ SS%E

Serum proteins

!acteria

%rauma

Shock

Epithelial cells

Endothelial cells

P/

acrophages

$ausative

,gents2

D+na(ic ti(e&course of t'e infla((ator+ response durin! durin! sepsis

I

n t e n s i t + o f

I n f l a ( ( a t o r + r e s p o n s

e


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*yperinflammatory

Response*ost "efense

*omeostasis

#mmunoparalysis• Overexpression of

proinflammatory cytokines and

second messengers• ? Underexpression of

antiinflammatory mediators• Decreased antioxidant defense• Pathologic PMN-E interactions• M!ltiple organ damage

• Depressed proinflammatory

cytokine expression• Decreased monocyte "#$-D%

expression &' ()*+, monocyte

deactivation• mm!nos!ppression - related

secondary sepsis

• mpaired micro.icidal f!nction• M!ltiple organ damage


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Pat'op'+siolo!+ of Sepsis


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BacteriaVirusu!"us#arasite$!dotoi!

&ost 'ells

(issue actors

actor V)) aactor V a

)!hibitio! of (hrombomoduli!

$lastase

ibri!

(*+1

#*)+1

eer*!oreia'acheiaNitric oide rele$!dothelial i!-u

)!flammatory .eso!se

(hrombotic.eso!se

ibri!olytic.eso!se

'ytokine Release$umor 3ecrosis FactorInterleukin 1, *, &, 10(4ygen radicals+roteases+rostaglandins

eukotrienes#radvkinin+latelet 6ctivating Factors

'oa"uloathy+dimer

(hrombi!

)!hibitio!*ctiated rotei! '

ecreased*!tithrombi! )))

Microascular(hrombosis

ibri! clot

uressio! ofibri!olysis


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Ho(eostasis Is ost In Sepsis

P,#-34 plasminogen activator inhiitor-35 %,a4 thromin activatale firinolysis

inhiitor6

*omeostasis*omeostasis

ProinflammatoryProinflammatorymediatorsmediators

Endothelial in7uryEndothelial in7ury

%issue factor expression%issue factor expression

%hromin production%hromin production

# n f l a m

m a t i o n

# n f l a m

m a t i o n

$ o a g u l a

t i o n

$ o a g u l a

t i o n

& i r i n o l y s i s

& i r i n o l y s i s

#ncreased P,l-3#ncreased P,l-3

#ncreased %,#ncreased %,aa

Reduced Protein $Reduced Protein $

8,ctivated Protein $8,ctivated Protein $

inhiits P,#-39inhiits P,#-39


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#ntravascular %hromosis#ntravascular %hromosis

&aust0 NEJM :;-;3?0 @==36


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, :;-year-old man (ith ilateral diffuse pneumonia0 gram-negative septicemia, :;-year-old man (ith ilateral diffuse pneumonia0 gram-negative septicemia

(ith thromocytopenia0 refractory hypotension0 and acute oliguric renal(ith thromocytopenia0 refractory hypotension0 and acute oliguric renal

failure6failure6

Images in Clinical Medicine, NEM, 3!5(19):139!, N"#. $, 2001.


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icroascular Alterations in Septic S'ock

%ancet 199$;351:1501&5


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Definition of S'ock

An acute co(pleJ pat'op'+siolo!ic state

of circulator+ d+sfunction w'ic' results in

a failure of t'e or!anis( to delier

sufficient a(ounts of oJ+!en and ot'ernutrients to satisf+ t'e reuire(ents of

tissue %eds


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SUPPK ' DEAND


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Definition of S'ock

• Inadeuate tissue perfusion to (eet tissue

de(ands

• Usuall+ result of inadeuate %lood flow and9o

oJ+!en delier+

• Shock is not a blood pressure diagnosis!!


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Definition of S'ock

• Inadeuate tissue perfusion

• Decreased oJ+!en suppl+

• Anaero%ic (eta%olis(

• Accu(ulation (eta%olic waste


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$'aracteristics of S'ock

• End or!an d+sfunction: – reduced urine output

– altered (ental status

– poor perip'eral perfusion

• eta%olic d+sfunction: – acidosis

– altered (eta%olic de(ands


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,'e $ardioascular S+ste(


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ec'anical Reuire(ents for

Adeuate ,issue Perfusion

• )luid

• Pu(p

• Fessels


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PreloadPreload

AfterloadAfterloadContractilityContractility

ResistancResistanc

Stroke VolumeStroke Volume Heart RateHeart Rate

Arterial BloodArterial BloodPressurePressure

OO22 DeliveryDelivery

OO22 ContentContent Cardiac OutputCardiac Output

xx

xx xx


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$lassification of S'ock

• H+poole(ic – de'+dration*%urns* 'e(orr'a!e

• Distri%utie

– septic* anap'+lactic* spinal

• $ardio!enic – (+ocarditis*d+sr'+t'(ia

• -%structie – ta(ponade*pneu(ot'oraJ

H+poole(ic S'ock:


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H+poole(ic S'ock:

$auses• )luid depletion

– internal

– eJternal

• He(orr'a!e – internal

– eJternal

$ di i S' k


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$ardio!enic S'ock:

$auses

ec'anical )ailure

– $ardio(+opat'+

– (eta%olic

– anato(ic

– '+poJia9isc'e(ia


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Distri%utie S'ock

A%nor(al Fessel ,one

1decreased afterload7


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Distri%utie S'ock:

$auses• Sepsis

• Anap'+laJis

• Neuro!enesis 1spinal7

• Dru! intoJication 1,$A*

calciu(* $'annel %locker7


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Septic S'ock

• Bacterial* iral* fun!al infection• .ra( ne!atie and !ra( positie %acteria

• Hi!' output failure: Lwarm shock # – )eer* tac'+cardia* tac'+pnoea* leucoc+tosis

• Inadeuate oJ+!en eJtraction – Hi!' S-/* eta%olic acidosis

• LCold shock #

• At+pical presentation in i((uno&co(pro(ised

patients• Dia%etes* $irr'osis* i((unosuppression


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SEP,I$ SH-$M

PREDISP-SIN. )A$,-RS

• EJtended 'ospitaliation

• Adanced a!e

• De%ilitatin! illness

• I((unodeficienc+ disorder

• Fentilator 2


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SEP,I$ SH-$M

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SEP,I$ SH-$M

$INI$A ANI)ES,A,I-NS

• Bleedin!• Oaundice

• Ileus• Skin c'an!es

SEP,I$ SH-$M


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SEP,I$ SH-$M

$INI$A ANI)ES,A,I-NS

Altered (entalstatus

,'er(al insta%ilit+

$ardiacd+sfunction

Respirator+

co(pro(ise

SEP,I$ SH-$M


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SEP,I$ SH-$M

DIA.N-S,I$ ,ES,S

Laboratory TestLaboratory Test ResultResult

WBCWBC Decreased, thenDecreased, thenincreasedincreased

HCTHCT Variable Variable

PLTPLT Decreased with DICDecreased with DIC

FibrinogenFibrinogen Decreased with DICDecreased with DIC

SEP,I$ SH-$M


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SEP,I$ SH-$M

DIA.N-S,I$ ,ES,S

Laboratory TestLaboratory Test ResultResultFibrin degradationFibrin degradationproductsproducts

Increased with DICIncreased with DIC

PT, PTT, TTPT, PTT, TT Prolonged with DICProlonged with DIC

pHpH DecreasedDecreased

Lactic acidLactic acid Increased (poorIncreased (poorprognostic actor!prognostic actor!

SEP,I$ SH-$M


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SEP,I$ SH-$M

DIA.N-S,I$ ,ES,S

Laboratory TestLaboratory Test ResultResultp"#p"# DecreasedDecreased

pC"#pC"# IncreasedIncreased

HC"$HC"$ DecreasedDecreased

%&%& IncreasedIncreased

SEP,I$ SH-$M


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SEP,I$ SH-$M

I$R-BI--.K S,UDIES

• Urine culture• Blood culture

• $ulture of

peritoneal fluid

• $ulture of a%scess

• Sputu( culture

A t f $i l ti


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Assess(ent of $irculation

arly !ate

Heart rate "ac#ycardia "ac#ycardia$

Bradycardia

Bloodpressure

%ormal Decreased

Perip#eral

circulation

&arm$Cool

Decreased$

'ncreasedpulses

Cool

Decreased

pulses

A t f $i l ti


46/72

Assess(ent of $irculation

arly !ate

nd(or)an*

Skin

Decreased

cap refill

Very decreased

cap refill

Brain 'rrita+le,

restless

!et#ar)ic,

unresponsive

-idneys Oli)uria Oli)uria, anuria


47/72


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Rivers, E. et al. N Engl J Med 2001;345:1368-1377


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"Except on few occasions,

the patient appears to diefrom

the bods response to

infection rather than from it" Sir illia( -sler – ;80<

,'e Eolution of odern edicine


51/72

/eptic /hock

Decreased0ol!me

DecreasedP!mp

1!nction

$.normal0essel

2one

I(proin! Stroke Folu(e:


52/72

I(proin! Stroke Folu(e:,'erap+ for $ardioascular Support

Preload 0ol!me

ontractility notropes

$fterload 0asodilators

Earl+&.oal Directed ,'erap+


53/72

+ p+

• .oals of t'erap+ wit'in first'ours are – $entral Fenous Pressure 4&;

(( H! 1;/&; in entilator p

– ean arterial pressure 2 6 H!

– Urine output 2 0> (9k!9'r

– Sc-/ or S-/ ?0=@

– if not ac'ieed wit' fluidresuscitation durin! first 6 'o

& ,ransfuse PRB$ to Hct 2 30and9or

& Ad(inister do%uta(ine 1(aJµ!9k!9(in7 to !oal

• #rade $

Earl+ .oal&Directed ,'erap+


54/72

;A6@B

::6:B

=

3=

@=

:=

;=


55/72

• )luid resuscitation (a+ consist ofnatural or artificial colloids or

cr+stalloids

• No eidence&%ased support for one

t+pe of fluid oer anot'er – $r+stalloids 'ae a (uc' lar!er olu(e of

distri%ution co(pared to colloids

– $r+stalloid resuscitation reuires (ore fluid to

ac'iee t'e sa(e endpoints as colloid – $r+stalloids result in (ore ede(a

)luid ,'erap+: $'oice of )luid

#rade C

$olloids


56/72

Al%u(in

• Hepatic production

• C 68*000

• 40= of $-P

• Seru( t;9/:

;4 'ours endo!enous

;6 'ours eJo!enous

.luid.luid


57/72

n!"ti! #ress$re

%tenden!& t" #$ll $nit' (a#illar(a#illar

&&

)&dr"stati! #ress$re

%tenden!& t" drive $nit'

.luid"ransport "ransport

Fasopressors


58/72

• ow dose dopa(ine s'ould not %e used for

renal protection in seere sepsis• An arterial cat'eter s'ould %e placed as soon

as practical in all patients reuirin!

asopressors

• Fasopressin (a+ %e considered in s'ock

patients t'at are refractor+ to fluid

resuscitation and 'i!' dose asopressors

• Infusion rate of 0>0;&0>0< units9(in in adults• a+ decrease stroke olu(e

Fasopressors

#rade

#rade

#rade

Inotropic ,'erap+


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• In patients wit' low cardiac output despite

adeuate fluid resuscitation* do%uta(ine(a+ %e used to increase cardiac output

• It is not reco((ended to increase cardiacindeJ to tar!et an ar%itraril+ predefined

eleated leel

• No %enefit fro( increasin! oJ+!en delier+ to

supranor(al leels %+ use of do%uta(ine

Inotropic ,'erap+

#rade

#rade

Alp'a&Beta eter


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Alp'a&Beta eter

ßß *"#a+ine*"#a+ine

E#ine#rineE#ine#rine

N " r e # i n e # , r i n

e

N " r e # i n e # , r i n

e

* " -

$ t a +

i n e

* " -

$ t a +

i n eN e " s & n e #

, r i n e

N e " s & n e #

, r i n e

Steroids


61/72

• Intraenous corticosteroids arereco((ended in patients wit' septic

s'ock w'o reuire asopressor t'erap+

to (aintain %lood pressure

• Ad(inister intraenous '+drocortisone /00&300 (!9da+ for ? da+s in t'ree or four

diided doses or %+ continuous infusion

• S'own to reduce (ortalit+ rate in patients

wit' relatie adrenal insufficienc+

Steroids

#rade

nnane, *. M, 2002; 2$$ (7): $

*P, axis during stress responStress, 'ytokines


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(%am+e'ts et al. NEM 200!;337:12$5)

↑

+

+

↓ '+bi!di!""lobuli!

↑ ocal ' actiatio!

$orticosteroid Insufficienin Acute Illness

$NS disease* $S use

$+tokine


63/72

• Adrenal insufficienc+ 1low

%asal seru( cortisol leel poor response to

cirticotropin7 is co((on in

criticall+ ill patients 1a%out

30=7* and 'i!'er in septic

s'ock 10&60=7

-

Pituitar+ apopleJ+* $S use

-

$S-inding

gloulin

↓↓

$+tokine* anest'etic*antiinfectie a!ents*

'e(orr'a!e* infection

+

↑ 1lucocorticoid resistance

Fasopressor t'erap+


64/72

Adeuate $-

BP at !oal

Adeuate perfusion

no+es

Inotropic t'erap+

no

+esRefractor+ septic s'ock Second asopressor Epinep'rine9p'en+lep'rine ow dose asopressin

Replace(ent dose of steroid

for relatie adrenal insufficienc+

no

("llenge' -M et al. CCM 200!;32:192$

SEP,I$ SH-$M

SUR.I$A IN,ERFEN,I-N


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SUR.I$A IN,ERFEN,I-N

• Draina!e ofa%scess

• De%ride(ent of

infected wound

• Re(oal of

infected or!an

SEP,I$ SH-$M

AN,IBI-,I$ ,HERAPK


66/72

AN,IBI-,I$ ,HERAPK

• Anti%iotics s'ould %e started

wit'in one 'our of dia!nosis

of sepsis9'+potension

i(proed surial

• Initial e(piric re!i(en s'ould

tar!et (ost likel+ pat'o!ens*e

• Reassess re!i(en after


67/72

SPE$IAIED AN,IBI-,I$S

• Anti&stap'+lococcala!ents

– ineolid

– Tuinupristin plusdalfopristin

– Fanco(+cin

• Anti&fun!al a!ents

SEP,I$ SH-$M


68/72

INIIIN. IN)AA,I-N

• Recominant human activated protein $

– In'i%its t'ro(%in

– In'i%its neutrop'il recruit(ent

– In'i%its apoptosis – I(proes surial in patients wit' (ulti&or!an

d+sfunction

– Dose & /< (icro!ra(s9k!9(in J 86 'ours

Actiated Protein $ in Seere Sepsis


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!rrent Management of

/evere /epsis and /eptic

NE8M 4))59 (33:677-;)7 NE8M 4))59 (33:677-;)7

%hromin

%hromomodulin

Protein

$ 8#nactive9Protein $ ,ctiv

lood Vessel!lood &lo(

Protein $

Receptor

Prot

S

*uman ,ctivated Protein $

Endogenous Regulator of $oagulation

Reco(%inant 'u(an Actiated Protein $


70/72

;;B

:3B

=B

3=B

@=B

:=B

;=B


71/72

RESPIRA,-RK SUPP-R,

Ad(inister oJ+!enonitor AB.s

Initiate (ec'anical

entilation earl+ Aoid %arotrau(aUse PEEP as

indicated

$ l i


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!rrent Management of

/evere /epsis and /eptic

$onclusion

kuliah uniba 18-4-12 sepsis & septic shok fp940325-e

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