sepsis and septic shock,mauritius, 2008

7/24/2019 Sepsis and Septic Shock,Mauritius, 2008

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Sepsis and Septic Shock, 2008

Prof J Cohen


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Sepsis and Septic Shock

Denitions

Epidemiology

Pathogenesis

Principles of management


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Denitions

Infection micro!ial phenomenoncharacterised !y an in"ammatoryresponse to the presence of micro

organisms or the in#asion of normallysterile host tiss$e !y these organisms

%acteraemia the presence of

!acteria in the !loodstream Septicaemia: no longer used

ACCP/SCCM Consensus Conference: Bone et al, Chest 1992 101:1!!


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Denitions

Sepsis systemic response to infectionmanifested !y & 2 of'emp ( )8oC or * )+oC - ( .0 !pm

-- ( 20 !pm or PaC/2* )2 mmg %C ( 12 10.34, * 5 10.34 or (106 !and form

Septic shock sepsis 7ith hypotensiondespite ade$ate "$id res$scitation, 7ith

perf$sion a!normalities that co$ld incl$de,!$t are not limited to, lactic acidosis,olig$ria, and3or ac$te mental stat$s9

ACCP/SCCM Consensus Conference: Bone et al, Chest1992 101:1!!


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SI-S and Sepsis

SI-S Systemic In"ammatory-esponse Syndrome

:e#er, le$cocytosis, organ fail$re

-ecognises di;c$lty of al7aysidentifying infection, !$t =CCP Consens$s ?$idelines

shock

BSIBSI


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"pidemiolog#


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here@s the infection A

Bernard $ %heeler &"'M ((:912, 199)


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hat@s the infectionA

P$re isolates, total n B 555 pts, +16 micro doc$mented

Cohen et al, ' *nfect +is 1999 10:11


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Martin et al: & "ngl ' Med 200(:(!:1-!


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Se#ere sepsis incidence and

mortality increase 7ith age

Angus Crit Care Med 29:1(01, 2001

>ortality

Incidence


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/rgan dysf$nction at time ofse#ere sepsis recognition

Bernard &"'M (!!:99, 2001


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-elationship !et7een mortality on ICand

the n$m!er of failed organs

.rom Breale# $ Singer, 2000


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Pathogenesis


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HOST PARASITE

P=>PPathogen associated

>olec$lar pattern

P--Pathogen recognition

receptor


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%acterial infection

Sepsis and septic shock

Ecessi#e host response

ost factors lead to cell$lar damage

/rgan damage

Death


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>olec$lar architect$re of the I- tosepsis

Bacterial factorsCell 7all componentsEtracell$lar prod$cts

Host factors

=c$ired imm$nityInnate imm$nity?enetic s$scepti!ility

Eector mechanisms4ymphokine storm

Chemokine acti#atione$trophil migration

asc$lar in"ammation


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Cohen, Nature: 2002 420:885


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otchiss et al, &"'M 200( (!:1(

m$ne acti#ation and imm$nos$ppression in sepsis


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Management


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>anagement of Sepsis

-ecognition

S$pporti#e care

So$rce control

=nti!iotics

Specic FadG$ncti#eHtherapy


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o7 likely is it that the diagnosis ofsepsis is !eing missedA Is it999

Extremely likely

Very likely

Somewhat likely

Not very likely

Not likely at all

Not sure

Total (n!"#$ Intensive %are Ph&sicians (n'#$

Ramsay, Crit Care 2004 8:R409.


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Initial res$scitation of sepsistherape$tic goals

Central #eno$s press$re 8 12

mmg

>ean arterial press$re & + mmg

rine o$tp$t 09 m43kg3h

Central #eno$s FSCH or mied

#eno$s oygen sat$ration & K06


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Dellinger, Crit Care >ed, 200) )1.5+

+ellinger, Crit Care Med, 200( (1:9!


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Iss$es in the rational choice ofanti!iotics

E::IC=CL

Spectr$m of acti#ity

Pharmacokinetics M

pharmacodynamics

Patterns of resistance'/NICI'L

C/S'


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Choosing anti!iotics in sepsis

'here is no, single, O!est regimen

Consider the siteof the infection

Consider )hich organismsmost oftenca$se infection at that site

Choose anti!ioticFsH 7ith the appropriatespectrum

=fter o!taining c$lt$res, gi#e anti!iotics$ickly and empiricall&atappropriate *ose


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Inadeuate treatment o! "loodstream in!e#tions

in#reases I$% mortality

Ibrahim et al, Chest 2000 118:146


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OonQanti!iotic therapy for sepsis

4o7 dose steroids

Intensi#e ins$lin therapy

tight glycaemic control

=cti#ated protein C

?oal directed therapy


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ERect of steroids on 28 day mortality

:a#o$rs treatment :a#o$rs control

-- 0988 F09K8 to 09..H p B 090)

Annane et al, BM' 200! 329:!0


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ERect of steroids on shock re#ersal

:a#o$rs treatment:a#o$rs control

-- 19+ F192K to 290)H p * 090001

Annane et al, BM' 200! 329:!0


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C/-'ICS

International, prospecti#e do$!leQ!lind -C' of hydrocortisone inpatients 7ith moderate se#ere

septic shock C 0 mg +h for d then tapering

to d 119 o "$drocortisone9

Primary EP 28 d mortality innonresponders

Sprung et al, & "ngl ' Med 200 358:111


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C/-'ICS Q -es$lts

No efecton 28 day mortality in7hole pop$lation or preQidentieds$!gro$ps

Did notre#erse shock in 7holepop$lation or preQidentieds$!gro$ps

Didred$ce the time to shock re#ersal

o signicant pro!lem 7ith s$perQinfection

Sprung et al, & "ngl ' Med 200358:111


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Intensi#e ins$lin therapy in critically illpatients

an den Berghe et al, &"'M 2001 345:1(-9

'ight glycaemic controlB80Q110 mg3dl F595Q+91 mmol3lH

I t i i li th i di l ti t


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Intensi#e ins$lin therapy in medical patientson IC

an den Berghe et al, & "ngl ' Med 200 354:!!9


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'he ISEP st$d of intensi e ins$lin


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'he ISEP st$dy of intensi#e ins$lintherapy and colloid res$scitation in

sepsis

Brunhorst et al, & "ngl ' Med 200 358:12-

St$dy terminated at rst safety analysis !eca$signicant hypoglycaemia in Ointensi#e gro$p

12916 #s 2916 p * 09001


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P-/ESS Drotrecogin alfa Facti#atedHTacti#ated protein CU in sepsis

P

value

A"solute redu#tion

in risk &'(aP$Pla#e"o

mortality &'(

All treated )ts

All treated )ts

strati!ied

All randomised

)ts

30.8

32.1

31.3

24.7

25.7

24.8

6.1

6.4

6.5

0.005

0.009

0.003

Bernard et al, & "ngl ' Med 2001 (!!:99


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Drotrecogin alfa Facti#atedH is not eRecti#ein ad$lts 7ith se#ere sepsis and a lo7 risk ofdeathV, and is associated 7ith an increased

rate of serio$s !leeding

A5raham et al, &"'M 200- (-(: 1((26 A++3"SS trial group

V =P=CE II * 2 orSingle organ fail$re


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P-/ESS Contin$ing de!ate

Is there condence in the !aselinecompara!ility of the pop$lations especially the s$!pop$lationsA

'here are #aria!le o$tcomesdepending on the se#erity marker$sed FI4+, =PII, S/:=H

'here is no conrmatory st$dy

=DD-ESS se#ere s$!gro$p did notsho7 !enet


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Early goal directed therapyEarly goal directed therapy

Purpose to adG$st cardiac preload,afterload and contractility to !alance

oygen deli#ery 7ith oygen demand "ntr# criteria patients in the

emergency dept 7ith se#ere sepsis M

shock Plan randomise to +h of E?D' !efore

transfer to IC

3i4ers et al, & "ngl ' Med 2001 (!-:1(


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Early ?oal Directed 'herapy

=3E admissions 7ith se#eresepsis3shock treated for + h !eforeIC transfer

Protocol designed to achie#e

CP & 8 12 mmg

>=P & + mmg

Sc#/2& K06

rine o$tp$t & 09 ml3kg9hr

3i4ers et al, & "ngl ' Med 2001 (!-:1(7))


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Early goalQdirected therapy in sepsis

Standard

thera)y

n*+,,

A#tive

thera)y

n*+,-

)

In hos)ital mortality &'(

All )atients

Severe se)sis

Se)ti# sho#k

/.0 ,-.0 -.--1

,-.- +.1 -.-/

0/.2 3., -.-

3i4ers et al, & "ngl ' Med 2001 (!-:1(

But86

Wnepectedl# high place5o mortalit#Wnusual ;"3< populationWSingle centre non75linded stud# design


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C$rrent contro#ersies

4o7 dose steroids A 3 otconrmed

Intensi#e ins$lin therapy A 3 otconrmed safety concerns

=cti#ated protein C 4icensed !$t

A re$ires conrmation ?oal directed therapy A3 -e$ires

conrmation


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O/n micro!es

Nor do I dou"t i! the most !ormida"le armies

ever heere u)on earth is a sort o! soldiers who!or their smallness are not visi"le4

Sir William etty, 1640


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sepsis and septic shock,mauritius, 2008

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