Sepsis and Septic Shock,Mauritius, 2008
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Transcript of 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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