Sept

icShoc
k

Tr
eat
ment

Appr
oac
hCons
ider
ati
ons

Patientswithseps i
s,s
everesepsi
s,ands eptics hoc
krequir
ehos pi
taladmi
ssi
on.Patient
swi t
h
seps i
swhor espondt oear
lyresuscit
ati
ont her apyi
ntheemer gencydepar
tment(ED)and
shownoev idenceofend-organhy poper
f usionmaybeadmi t
tedtoageneralhospi
talunit
,
optimal l
yonet hathascl
osenursingobser vationandmonitori
ng.Suchpati
entsdonotr equi
re
i
nv asivehemody namicmonitori
ngandus uallydonotrequir
eadmi ss
iontoanint
ens i
vecare
unit(ICU).

Pati
entswhodonotr espondt oini
tialEDt reatment( i
e,whohav erecurrenthypotensi
on
despi
teadequatef
lui
dc hall
enges)andt hos ewhoar ei ns epti
cshockr equireadmissi
ontoan
ICUforconti
nuousmoni t
oringandc ontinuedgoal -direc
t edtherapy.I
fanappr opr
iat
eICUbed
orphysi
ciani
snotav ail
able,thepatientshoul dbet ransferredwithadv ancedli
f es
upport
monitori
ngtoanotherhos pitalwit
ht heav ail
ableresourc es.

Thereissigni f
icantc ontroversysurroundinggoal -
directedt herapy(EGDT)i nthemanagement
ofseveres epsisands epticshock.EGDTwaspr evi
ous l
yev aluatedinas mall,si
ngl
e,
randomizedt r
ialatas ingleinsti
tuti
on.[68]Subs equently,threenewer ,l
arge,multi
c enter
randomizedt r
ialswer eper f
ormedi ntheUni t
edSt at
es( ProCESS[ ProtocolizedCareforEarly
Septi
cShoc k]),
[57]Aus t
rali
a(ARI SE[Aus tral
asi
anRes us ci
tationInSeps i
sEv al
uati
on] )
,[58]
andtheUni tedKi ngdom ( ProMISe[Protoc oli
sedManagementI nSeps i
s])
.[59]

InthePr oCESSt ri
al,1341pat i
entswi t
hs epti
cs hockin31ac ademi chospit
alEDsr ecei
ved
treatmentbas edononeoft hreeappr oaches:protocol-
bas edEGDT;pr otocol
-bas eds t
andard
therapythatdi dnotr equi
rethepl acementofac entr
alvenousc atheter
,administrationof
i
not ropes,orbloodt ransf
usions;ors t
andardc are.
[69,70]Nos ignifi
cantdif
ferenc esbetween
groupswer efoundf or90-daymor tali
ty,1-y
earmor tali
ty,ortheneedf ororgans uppor t
.

Similarfindingswer erepor tedfrom bot htheARI SEandt heProMISetrial

s .I
mpor tanttonote,
meas uringlactate,targetingSc vO2v alues,andi
ns er
tionofac entr
alvenousc atheterwer enot
assoc i
atedwi thimpr ovedout comes .Whatwasi mpor t
antwast hedir
ectandaggr essive
i
ndiv i
dual i
zedc areeachpat ientreceived,incl
udi
ngear lybact
eriol
ogicculturesofappr opri
ate
sit
es( eg,blood,ur i
ne,s putum),earlyandc or
rec
ti ns
titut
ionofbroad-spec tr
um ant i
bioti
cs,
restorationofbl oodpr essure,andr eversalofevi
denc eofend-organper f
us i
on.Thes efi
ndings
ar
ereas
onablewhenconsi
deredwi
thi
nthecontextofac
utecaremedic
iner
esus
cit
ation
pr
inc
ipl
es.Namel
y,st
abil
iz
ethepat
ient
,rev
ersethecauseofshoc
k,anddonoaddi
tionalhar
m.

Goal
sandpr
inc
ipl
esoft
reat
ment

Thet
reat
mentofpat
ient
swi
ths
ept
ics
hoc
khast
hef
oll
owi
ngmaj
orgoal
s:

St
artadequat
eant
ibi
oti
cther
apy(
properdos
ageands
pec
trum)asear
lyaspos
sibl
e

Res
usci
tat
et hepati
ent
,usi
ngsuppor
tiv
emeas ur
est
ocor
rec
thy
pox
ia,hy
pot
ens
ion,and
i
mpair
edtiss
ueox y
genati
on(hy
poperf
usion)

I
dent
ifyt
hes
our
ceofi
nfec
tion,andt
reatwi
thant
imi
crobi
alt
her
apy
,sur
ger
y,orbot
h(s
our
ce
c
ontr
ol)

Mai
ntai
nadequat
eor
gansyst
em func
tion,guidedbycar
diov
ascul
armoni
tor
ing,andi
nter
rupt
t
heprogres
siont
omult
ipl
eorgandys
functionsyndr
ome( MODS)

Managementpr
inc
ipl
es,bas
edont
hec
urr
entl
it
erat
ure,i
ncl
udet
hef
oll
owi
ng:

Ear
lyr
ecogni
ti
on

Ear
lyandadequat
eant
ibi
oti
cther
apy

Sour
cec
ont
rol

Ear
lyhemody
nami
cres
usc
itat
ionandc
ont
inueds
uppor
t

Propervent
il
atormanagementwi
thl
owt
idalv
olumei
npat
ient
swi
thac
uter
espi
rat
orydi
str
ess
sy
ndr ome(ARDS)

Ini
ti
alt reatmenti ncl
udessuppor tofrespirat
oryandc irc
ulator
yfunc t
ion,s uppl
ementaloxy
gen,
mec hani c
alv enti
lat
ion,andv ol
umei nfusi
on.Treatmentbey ondt heses upporti
vemeasures
i
ncludesant i
mi cr
obialther
apyt arget
ingt hemostlikelypathogen,remov alordrai
nageofthe
i
nfec t
edf oci
,treatmentofc omplicati
ons,andinterventionstopreventandt r
eatef
fectsof
harmf ulhos tresponses.Sourcecontrolisanessentialcomponentofs epsismanagement.

Venousac
ces
s
Inallcasesofs epti
cs hock,adequat ev
enousac cessmus tbeensuredforv ol
umeresuscit
ati
on.
Whens epsisi
ss uspected,2large-bore(16-gauge)intr
avenous(I
V)li
ness houldbeplacedif
poss i
bletoallowadmi nistr
ationofaggr essi
vefl
uidr es
uscit
ati
onandbr oad-spect
rum
antibi
otics.Centralvenousac cessisusefulwhenadmi nis
teri
ngvasopressoragentsandin
establi
shingas tablevenousinf usi
onsitebutisnotmandat ory.

Ifthehy potens iondoesnotr espondtoac r

y st
all
oidfl
uidbol usof30mL/ kg(1-2L)ov er30-60
mi nutesori ffluidscannotbei nfusedrapidlyenough,ac entralvenouscatheters houldbe
plac edi nthei nternalj
ugul arorsubcl
avianv ei
n.Thiscatheterallowsadmi ni
s t
rationof
medi cationc entrall
yandpr ovi
desmultipl
epor tsforrapi
df l
ui dadmini
stration,antibi
oti
cs,and
vas opr essorsifneeded.I talsoall
owsmeas urementofc entralvenouspres s
ur e(CVP),a
surr ogatef orv olumes tatus,i
fCVPmeas urementc apabil
it
yi savail
abl
e.

Ifanint
ravasc
ularacc
es sdev
icei
ssuspect
edasthesourceofsev
eres
epsi
sorsept
icshoc
k,
alt
ernat
ivevascul
araccessmustbeobtai
ned,andt
hes us
pectdevi
cemus
tthenberemoved.

Ur
inar
ycat
het
eri
zat
ion

Anindwel
linguri
naryc athetershouldbepl
aced.Inal
lpat
ient
swithsepsi
s,uri
neoutput(UOP),
amarkerforadequater enalperfusi
onandcardi
acoutput
,shoul
dbec l
osel
ymoni t
ored,as
shoul
drenalfunct
ion;mor tali
tyisgreat
lyi
ncr
easedinpati
entswit
hurosepsi
sands evere
sepsi
sorseptics
hoc k.Nor malUOPi nanadulti
s0.5mL/kg/hrormore,
[11,60]equiv
alentt
o
about30-
50mL/ hrformos tadul t
s.

Anyabnor mali
ti
esinUOPs houl
dpromptas s
es s
mentoft headequacyofc i
rcul
ati
ngbl ood
volume,cardi
acoutput,andbloodpres
s ure;theseshouldbecorrec
tedifinadequate.Aswith
sepsi
sinothersit
es,earlyandappr
opriateiniti
ati
onofant i
micr
obialther
apy aswel las
i
dent i
fi
cati
onandmanagementofanyur i
naryt r
actdis
ordersisessenti
al.
[54]

I
ntubat
ionandmec
hani
calv
ent
il
ati
on
Mostpat i
ent swiths epsi
sdev elopr espir
atorydis
tressasamani fest
ationofs ev
eresepsisor
sept
ics hoc k.Thelungi njuryi sc haracteri
zedpathologi
c al
lyasdi
ffusealveolardamage( DAD)
andrangesf rom ac utel
ungi nj ury( ALI)
ormi ldARDS,byt heBerl
inDef i
nition[10]t o
moder ateors ev
ereARDS( seeBac kground).Thesepatientsneedintubationandmec hanical
vent
ilati
onf oroptimalres pi
r ator ysuppor t
.Int
ubationshouldbec onsi
der edear l
yinthec our
se
ofprogr essingsev ereseps i
sands epti
cs hock.

Direc
tdel i
veryofox ygeni
ntothet r
acheaataf rac
tionofins pi
redox y
gen(FIO2)of1isfar
superiortodeli
veryviaanonrebreatheroxygenmas k.Mec hanicalv
entil
ati
on,withappr
opri
ate
sedation,al
soeliminatest
hewor kofbr eat
hingaswel lasdec r
easesthemet abol
icdemandsof
breathing,whic
hac countsforabout30% oft ot
almet abol
icdemandatbas eli
ne.

Alveolarov erdistenti
onandr epeti
tiveopeningandc l
osingofal veol
idur i
ngmec hani
cal
ventil
ationhav ebeenas soci
atedwithani ncreas
edi ncidenceofARDS.Lowt i
dalvol
ume
ventil
atorys trategieshavebeenus edtomi nimizethist y
peofal veolarinj
ury.The
recommendedt i
dalv ol
umeis6mL/ kg,withplateaupres sureskeptatorbel ow30mLH2
O.[11,60]Pos iti
veend- expi
rator
ypr es
sure(PEEP)i srequiredtopr eventalv
eolarcol
laps
eat
end-ex pir
ation.[71]

Gener
alTr
eat
mentGui
del
ines

Themaj orfocusofresus c
itationfrom septi
cs hockisons upporti
ngcardi
acandrespir
atory
functions.Theot herorgans ys t
emsmayal sor equir
eat t
entionandsupportduri
ngthiscrit
ical
period.Pat i
entsi
ns epticshoc kgeneral
lyrequireintubati
onandas si
stedvent
il
ati
onbec ause
respir
at oryfai
lur
eeitherispr esentattheons etofill
nessormaydev elopduri
ngitscourse.
Correc ti
onoft heshocks tateandabnor malti
s s
ueper f
usionisthenextst
epinthetreatment
ofpat ientswithsepti
cs hock.

In2004,thefir
stsetoff ormal tr
eatmentguidelinesfors epti
cshockwerepubli
shed.[72]
Theseguideli
nes,knownast heSur vi
vingSepsisCampaign,wer eformul
atedbyan
i
nternati
onalconsensusgr oupt hatwasc ompos edofex pertsfr
om 11organi
zati
ons ,i
ncl
udi
ng
theSocietyofCrit
icalCareMedi cine(SCCM),theAmer icanCol l
egeofChestPhysi
cians(ACCP)
,
theEuropeanSoc i
etyofI ntensi
v eCareMedicine(ESICM) ,andtheAmericanColl
egeof
EmergencyPhy si
cians(ACEP) .Theseguideli
nesar er
eviewedandupdat edperi
odically
.

TheSur
viv
ingSeps
isCampai
gngui
del
ineswer
elas
tupdat
edi
n2012,andt
hec
urr
entv
ers
ions
ref
lec
tt heopini
onofar eas
onableapproacht othetr
eatmentofs epti
cshock.
[11]Thereader
i
senc ouragedtochec
kt heSepsi
sCampai gnsWebsiteperi
odical
lyfornewinf
ormation.
Speci
fical
ly,wi
ththerecent
lyl
argecli
nicaltr
ial
sinthemanagementofs ept
icshockcompleted,
speci
ficrecommendationsmaybedegr aded.Thosearehighl
ightedbelow.

Thefir
st6hoursofres
usci
tati
onofacr
iti
cal
lyi
llpati
entwi
thseps
isors
ept
ics
hoc
kar
e
cri
ti
cal
.[11]Thef
oll
owingshoul
dbecomplet
edwi thi
n3hours
:

Obtai
nt helac
tatel
evel(
Althoughr
ecommended,thethr
eerecenttri
alsshowedthatlact
ate-
gui
dedt her
apyhadnoi mpactonsurv
ival
.St
il
l,l
act
atel
evel
sparal
lelsept
icshockseveri
tyand
hav
epr ognosti
cimpli
cati
on.)

Obt
ainbl
oodc
ult
uresbef
oreadmi
nis
ter
ingant
ibi
oti
cs

Admi
nis
terbr
oad-
spec
trum ant
ibi
oti
cs

Admi nister30mL/ kgofc r

yst
all
oidsolut
ionforhy potensi
onorforlac
tatelevelsof4mmol /L
orhigher( Again,althoughmos tpati
entspresenti
ngwi thsev
eresepsi
sar einaf uncti
onal
hypov olemicstate,requir
ingfl
uidresusc
itat
ion,caref
ulmonitor
ingofr i
ghtv entri
cul
arvol
ume
overl
oadi ses
sent i
aliflar
gequantil
esofflui
dar etobegi v
enquickl
y,toavoidinduc i
ngacute
corpul monale.)

Thef
oll
owi
ngs
houl
dbec
ompl
etedwi
thi
n6hour
s:

Administ
ervasopr essorsforhy potensi
onthatdoesnotres
pondt oini
tialf
lui
dres
uscit
ati
onto
maintai
nameanar t
erialpressure(MAP)of65mm Hgorhi gher(Recents t
udi
esshowedthe
val
idi
tyofthe70- 75mm Hgl owermeanar ter
ialpr
ess
uretargetor80-85mm Hgi nthose
pat
ientswit
hpr eex i
stinghy pertensi
on.
)

Ifhypotensi
onpersist
sdes pit
ev ol
umer esusci
tati
onort heinit
iall
actat
el eveli
s4mmol /
Lor
higher,t
henmeas urecentralvenouspressure(CVP)(ai
mi ngfor8mm Hg) ,measurecentral
venousox y
gens at
urati
on( ScvO2)(aimingfor70%) ,andnor mali
zelactatelevel
s(These
recommendat i
onswi l
lprobablybemodi fi
edinlieuofthef i
ndingsthatCVPdoesnot
repres
entanef f
ecti
vet ar
get.Seebelowaboutt hevenoarter
ialPCO2gr adientanalysi
sas
beingamor especif
icmeas ureoftiss
uehy poperfusi
on.)

TheRoy alCol
legeofObstetr
iciansandGy naecologi
sts(RCOG)rec ommendsf ol
l
owi ngthe
Survi
vi
ngSeps isCampai
gngui del i
nesformanagingpregnantwomenwi t
hsepsi
sors epti
c
shock.
[73]Treatmentst
rategiesi ncl
udeear
lyr ec
ogniti
onandres usci
tati
onmeas ur
es,
support
ivecare,r
emovalofthes epti
cfocus,admini
strat
ionofbloodpr oduc
tsasneeded,and
thr
omboprophyl
axi
s,aswel
last
hei
nvol
vementofamul
ti
dis
cipl
inar
yteam.
[11,73](
SeeShoc
k
andPr
egnancy.
)

Althoughnotpar toftheguideli
nes ,muchat tentiont omeas uri
ngnotonlyeffecti
veoxygen
deliverybutalsoorganbloodf l
owhasemer gedasr easonabl eparameterstogradeshock
sever i
ty.Cl
earl
y ,al
owSc vO2c anoc c
urfrom r educedc ardiacout put
,butitcanalsoocc
ur
from s ever
eanemi a(orhemogl obinopathies)andhy poxemi a.Simil
arl
y,anormalorhigh
Sc v
O2mayr ef
lectmetaboli
cbloc k,shunt,ors amplinger rors.

Toaddr essmanyoft heseerrorsones houldcalculat

et hear teri
alt
ocentralvenousPO2
gradi
ent( Pa-vO2).Si
nc eviabl
et i
ssuesproducec arbondi oxideasanendpoi ntofmet aboli
sm,
end-capil
laryPCO2i ncreasesast i
ssuebloodflowdec reases.Thec entr
alvenous t
oarteri
al
PCO2gap( Pv-aCO2)as sessesbloodflow.Final
ly,lactate,al
thoughi nsensi
t i
veasamar kerof
i
schemi a,isst
illanexcell
entmeas ureoft i
ssueinjuryandt hei nfl
ammat orys t
ate.Thus,thePv-
aCO2/ Pa-vO2r ati
ocanbeus edtoas sessthesev eri
tyofc ir
culatoryshockins epsi
s.[
74,75]

Res
pir
ator
ysuppor
t

Aniniti
alasses
smentofairwayandbreathi
ngisv
italinapati
entwi t
hs epti
cs hock.
Supplementaloxy
gens houl
dbeadmi ni
ster
edtoallpati
ent
swi thsuspecteds epsi
s.Ear
ly
i
ntubationandmec hani
calvent
il
ati
onshouldbestrongl
yconsider
edf orpatientswithanyof
thefoll
owing:

Ox
ygenr
equi
rement

Dy
spneaort
achy
pnea

Per
sis
tenthy
pot
ens
ion

Ev
idenc
eofpoorper
ipher
alper
fus
ion

Ci
rcul
ator
ysuppor
t

Pati
ent
swi t
hsuspectedsepti
cshoc
kr equi
reaniniti
alcry
stal
loi
dflui
dc hall
engeof30mL/ kg
(1-
2L)over30-60minutes,wit
haddit
ionalf
lui
dc hal
lenges.(
Aflui
dc hall
engec onsi
stsofrapid
admini
str
ati
onofv ol
umeov erapar
ticul
arperi
od,foll
owedbyas sess
mentoft heresponse.)
(
SeeFl
uidRes
usc
itat
ion.
)

Admi ni
strati
onofc rystal
loids ol utioni stit
ratedtoagoalofadequat etis
sueper fus i
on.IfCVP
i
sus edt otargetres
usc it
ation, its houl dbeus edasas toppingr ul
e.If
,duringf l
uid
resusci
tati
on,CVPr apidlyinc reas esbymor ethan2mm Hg,abs ol
uteCVPgr eatert han8-12
mm Hg,ors ignsofvolumeov er load( dy spnea,pulmonaryr al
es,orpulmonar yedemaont he
chestradiograph)occur,f l
uidi nfus ionaspr imarytherapyneedst obes topped.Pat i
entswith
septi
cs hockof tenr
equi r
eat ot alof4- 6Lormor eofcrystall
oidsoluti
on.Howev er,CVP
meas ur
ements houl
dnotbeent irelyr eli
edupon,bec auseitdoesnotc orrelatewi t
h
i
ntravascularvolumestat usorc ardi acv ol
umer esponsiveness.
[76]

Somes tudieshaveus ednoninvasiv

emeansofes t
imatingCVPf orex ample,ultr
asonography
tomeas ureinferi
orv enac avadiamet erasas ur
rogat eforvol
umes tatus.Nagdevetalus edthe
dif
ferencebetweeni ns pi
ratoryandex pi
ratorycavaldiameter(
thecav ali
ndex )topredi
ctCVP
andfoundt hata50% di f
ferencepr edictedaCVPl owerthan8mm Hgwi t
hbot hasensit
ivi
ty
andas pecifi
ci
tygr eaterthan90%. [77]Si mil
arl
y ,vari
ati
onsinthi
sdi ameterc hangewith
respi
rati
onc orrel
atedwi thv ol
umer esponsiv
enes s.

UOPs houl dalsobemoni toredasameas ureofdehy drat i

on.UOPl owert han30- 50mL/ h
shoul dpr omptf urt
herf luidr esuscitationorot hermeas urest oi nc reasecardiacout puti na
nonf luid- r
espons i
v epat i
ent .Impor tantt onote,dur ingf luidr es usc i
tati
onf orsev eres epsi
s,
i
nc reas edi ntra-
abdomi nalfluidacc umul ationandi leusof t enoc curandc aninduc ei ncreasesi
n
i
nt ra-abdomi nalpres sure.Ifintra-
abdomi nalpressurei sgr eat ert han12mm Hg,i nt ra-
abdomi nal hypertens i
onex i
s ts
.Sinc er enalperfusi
onpr essur ec anbeappr ox i
mat edasmean
arterialpr essuremi nusCVPori ntra- abdomi nalpres sur e(whi chev eri shi
gher ),l
owUOPmay
refl
ec tlowr enalper f
us i
onpr essure.I ngener al
,target ingar enalper fusi
onpr essur eof70- 75
mm Hgs ustainsadequat erenalbloodf l
owi nseveres epsisunl esspr eexist
inghy per tensionis
pres ent,inwhi c
hc as etarget i
ngahi gherr enalperfus ionpr essur eof80- 85mm Hgi s
i
ndi cated. [78]

Giventhatt hird-spac i
ngofi ntr
av ascul
arf l
uidisahal
lmarkofs eptics hoc k,itmakess ense
thatadmi nistrat
ionofc oll
oidsolutionmi ghtbebenefi
cial
.Howev er,althoughc ol
loi
d
resusci
tationwi thal buminhasnotbeens howni nmanymet a-anal ysest ohav eanyadv antage
overisotonicc rystall
oidresuscit
at i
on(isotonicsodi
um chlor
ides olutionorl actatedRinger
solut
ion)int hisset ti
ng,[79]Delaneyetalf oundadjunct
ivealbumi nr esus cit
ati
ont opr ovi
dea
stati
sti
callysignifi
c antmor tal
it
ybenef i
ti nrelat
iontootherregimens .
[80]
IntheSal
ineversusAl bumi nFluidEv al
uation( SAFE)tri
al,inwhi chabout1200of7000I CU
pati
entswhor equiredf luidresuscitati
onhads everesepsis,noov eralldi
ffer
encebetweent he
2treat
mentgr oupswass een.[81]Howev er,theinvesti
gat orsnotedat r
endt owardimproved
outcomeinpat i
entswi thseveres epsiswhor ecei
ved4% al bumi nratherthannor malsal
ine.
Thedataareinconc lusive,especiall
ywi thregar dtotheinitialres
uscitati
onphas eforsepti
c
shockintheED;t her efore,cry
s t
alloidfl
uidr esusci
tati
oni sr ec
ommended.

Thec urrentSur vi
vingSeps i
sguidelinesrec ommendr apidadmi nist
rat ionofani nit
ialflui
d
challengewi th30mL/ kgofc r
ystall
oids oluti
on.[ 11]Albumi ns houldbeus edonl ywhen
subs tant i
alamount sofc ryst
all
oids olut
ionar er equired.Hy drox yet
hy l starchs olut
ionsar enot
recommended. [11]( SeeGoalsofHemody nami cSuppor t.)Sev eralrec entr et
r ospecti
v eand
smal lerpr ospecti
vec li
nic
altri
alshav eunder scoredt her i
skt hat0. 9NNaClhasasapr imary
resus ci
t at
ionf l
uid.Itcauseshyper c
hloremi cmet abol
icac i
dos isandi sas sociatedwi than
i
nc reas edmor t
ali
tyr el
ati
vetobal anceds altsolut i
ons(eg,pl asmal yte).[82]

Cor
rec
tionofanemi
aandc
oagul
opat
hy

Hemogl obinlevelsaslowas7g/ dLarewelltol

eratedbypat
ient
s,andtransfusionisnot
requiredunlessthepat i
enthaspoorc ardi
acreserveordemonstr
atesevi
denc eofmy ocardi
al
i
s chemia.Thromboc ytopeniaandc oagul
opathyarecommoni npati
entswiths epsi
s;these
patientsdonotr equirereplacementwithplat
elet
sorf r
eshfr
ozenplasma(FFP)unl es
st hey
dev el
opac t
ivecli
nicalbleeding.

Ifhemogl obinlevelsfallbelow7g/ dL,redbloodc ell(RBC)transfusi

onisrecommendedt oa
targethemogl obinr angeof7- 9g/ dL.[11]Ev eni nt heabsenceofappar entbleeding,patients
withs ev
er esepsisshoul dreceiv
epl atelettr
ans fusioni fpl
atel
etc ountsfal
lbelow10109/ L
(10,000/L).Plat
elett r
ans f
usionmayal sobec ons i
deredwhenbl eedingr i
skisincreasedand
platel
etc ountsarebel ow20109/ L( 20,
000/ L).[11]Patientswhoar etounder gos urgeryor
otherinvas i
veprocedur esmayr equirehigherpl ateletcounts(eg,50109/ L[ 50,000/L]).

Otherpoi
ntstoc ons
iderwi
thr
espec
ttot
headmi
nis
trat
ionofbl
oodpr
oduc
tsi
ncl
udet
he
fol
lowi
ng[11,60]:
Erythropoiet
inisnotrecommendedfors
peci
fictr
eatmentofanemiaas
soci
atedwi
thsever
e
sepsis
;rather,i
tshouldbegivent
osuchpat
ientsforot
heraccept
ablei
ndi
cati
ons(
eg,anemia
associ
at edwithrenalf
ail
ure)

FFPi snotrec
ommendedf orthecorr
ecti
onofl
aborat
oryc
lot
tingabnor
mal
it
iesunl
ess
bleedingi
spresentori
nvasi
veprocedur
esar
eplanned

Ant
ithr
ombi
nagent
sar
enotr
ecommendedf
ort
reat
mentofs
ever
eseps
isands
ept
ics
hoc
k

Recombinantact
ivat
edprot
einC(
rhAPC)i
snol
ongerav
ail
abl
efort
reat
ingpat
ient
swi
th
sev
eresepsisorsept
ics
hock

Ant
imi
crobi
alt
her
apy

IVanti
biotictherapyshouldbei ni
ti
atedwithinthefi
rsthouraftertherec ogni
ti
onofs ept i
c
shockorsev eresepsis
;delaysinadminis
trati
onareass ociat
edwithinc
r easedmor t
ali
ty.
[ 5,11,
60]Select
ionofant ibi
oticagentsisempiri
c,basedonanas ses
smentoft hepati
ent
s
underl
yinghos tdefenses,thepotenti
alsourceofinf
ect i
on,andthemos tli
kel
yresponsible
organi
sms .(SeeEmpi ri
cAnt i
microbi
alTherapy.
)

Whent hesour
c eisunknown,t heant i
biot
icchos enmus tbeabr oad-spect
rum agentthat
cover
sgram-pos it
ive,gr
am-negative,andanaer obi cbact
eri
a.Inaddi
tion,consi
derat
ionmus t
begiventopathogenswi thantibi
oticresi
stance,s uchasmethici
ll
in-
resist
antStaphyl
oc oc
cus
aur
eus(MRSA),Ps eudomonass pecies,andgr am- negati
veorganis
mswi thextended-spect
rum
bet
a-lact
amase( ESBL)acti
vit
y.

Pati
entswhoar eatris
kforthesetypesofi nfec
tionar ethosewithrecent,prolonged,or
multi
plehospit
ali
zati
ons.The2012Sur vi
vi
ngSeps i
sCampaigngui del
inesrecommend
combinati
onempi ri
ctherapyforneutr
openi cpatientsaswellasforthosewi thdiff
icul
t-t
o-
tr
eat,mult
idrug-r
esist
antmi c
roorgani
sms ,suchasAc i
netobact
erandPs eudomonas .[
11]

Temper
atur
econt
rol

Fevergeneral
lyr
equiresnotreat
ment,exceptinpatientswhohavelimi
tedc ar
diov
ascul
ar
reser
veasac onsequenceofincr
easedmet abol
icrequir
ements.Anti
pyreti
cdrugsandphysic
al
cooli
ngmet hods,suchasspongingorcooli
ngblankets,maybeus edtolowerthepati
ent
s
temperatur
e.
Externalcool i
ngisanothermet hodoff evercontr
olt hathasbeenr eport
edt obes afeandto
decreasev asopressorrequi
rement sandear l
ymor t
alityinpatient
swi t
hseptics hock.I
na
multicent
er ,randomized,control
ledstudyc ompri
singf ebri
lepati
entswiths epticshockwho
requiredvas opres
sors,mec hani
calventil
ati
on,ands edation,thegroupthatr ec
eivedexter
nal
cooli
ng,asc omparedwi ththegroupt hatdidnot,exhibitedthefoll
owing[83]:

Si
gni
fi
cant
lyl
owerbodyt
emper
atur
eaf
ter2hour
s

Si
gni
fi
cant
lymor
ecommonoc
cur
renc
esofs
hoc
krev
ers
ali
ntheI
CU

Si
gni
fi
cant
lyl
owerday
-14mor
tal
it
y

Althougha50% dec r
easei
nt hevas
opres
s ordosewassigni
fi
cantl
ymorecommonaft
er12
hoursofex t
ernalc
ooli
ngtreatment
,thesamer esul
twasnotfoundaf
ter48hour
softhi
s
therapy.
[83]

Met
abol
icandnut
rit
ionals
uppor
t

Pati
entswit
hs ept
icshockdev
elopelec
trol
yteabnor
malit
ies.Potas
sium,magnes
ium,and
phosphat
elevelsshoul
dbemeas ur
edandc or
rect
edifdefi
ci
ent .

Pat i
entswit
hs ept
icshockgenerall
yhavehighprot
einandenergyrequi
rements.Alt
hougha
briefperi
od(sever
aldays)withoutnut
rit
iondoesnotcausedel
eter
iouseff
ects
,pr ol
onged
starvat
ionmus tbeavoided.

Earl
ynut r
iti
onals
upportisofcri
ti
c ali
mportanc
einpati
ent
swi t
hsepti
cs hock.Theor
alor
enteralr
outeispref
err
ed,unles
st hepati
enthasanil
eusorotheri
ntes
tinalabnormal
it
y.
Gastropares
isiscommonlyobservedandc anbetr
eatedbyadmini
ster
ingmot il
it
yagentsor
placi
ngas mall
-bowelfeedi
ngtube.

Dimini
shedbowelsoundsar
enotac ontr
aindi
cat
iont
oatri
alofenter
alnutr
iti
on,though
motil
it
yagentsorasmall
-bowel
feedingtubemaybenec
essary.Thebenef
itsofenteral
nutr
iti
onareasfol
lows:
Pr
otec
tionofgutmuc
osa

Pr
event
ionoft
rans
loc
ati
onofor
gani
smsf
rom t
hegas
troi
ntes
tinal
(GI
)tr
act

Reduc
tionoft
hec
ompl
ic
ati
onr
ate

Lowerc
ost

The2012Sur
vivi
ngSepsi
sCampai
gngui
del
inesrec
ommendus
ingnut
rit
ionals
uppor
twi
thout
spec
ifi
cimmunomodulat
ings
uppl
ement
ati
on.[
11]

Goal
sofHemody
nami
cSuppor
t

Shockrefer
st oast at
eofinabil
it
ytomaintai
nadequateti
ssueperfusi
onandoxygenat
ion,
whichult
imatelycausescel
lul
ar,andthenorgansyst
em,dysfunct
ion.Ther
efor
e,thegoal
sof
hemodynami ctherapyar
er est
orati
onandmai nt
enanceofadequateti
ssueper
fusi
onsoast o
prev
entmul t
ipleorgandysfuncti
on.

Car
efulcl
ini
calandi
nvasiv
emoni tor
ingisr
equi
redf
orass
ess
mentofgl
obalandr
egi
onal
per
fusi
on.Shockatthebeds i
deisdefi
nedbyanMAPlowert
han60mm Hgoradecr
easein
MAPof40mm Hgf rom basel
ine.

Elevat
ionofthebl oodlactatelevelons eri
almeas urement soflactatec
anindi cat
einadequate
ti
s s
ueperfusi
on.Inaddi t
ion,mi x
edv enousox yhemogl obinsaturati
onser
v esasani ndi
catorof
thebalancebetweenox y
gendel iveryandc ons umpt ion.Adec reaseinmaximalv enousoxygen
(MVO2)c anbes econdaryt odecreasedc ardiacout put;howev er,maldi
str
ibutionofbloodf l
ow
i
npat i
entsexperiencingsepticshoc kmayar t i
fic
iall
yel evatetheMVO2l evels.AnMVO2ofl ess
than65% generallyindi
catesdec reasedtissueper fus i
on.

Regionalper
fusi
oni
npatient
swi t
hs ept
icshocki
sev
aluat
edbyasses
singtheadequac
yof
organfuncti
on.I
ndi
cat
ionsofinadequateperf
usi
onmayincl
udeanyofthefol
lowi
ng:

Ev
idenc
eofmy
ocar
diali
schemi
a

Renaldy
sfunc
tion,mani
fes
tedbydec
reas
edUOPori
ncr
eas
edc
reat
ini
nel
evel
s
Cent
ralner
vouss
yst
em (
CNS)dy
sfunc
tion,i
ndi
cat
edbyadec
reas
edl
evel
ofc
ons
cious
nes
s

Hepat
ici
njur
y,s
hownbyi
ncr
eas
edl
evel
soft
rans
ami
nas
es

Spl
anc
hni
chy
poper
fus
ion,mani
fes
tedbys
tres
sul
cer
ati
on,i
leus
,ormal
abs
orpt
ion

Hemodynamicsupporti
ns ept
icshockisprovidedbyr est
ori
ngtheadequat
eci
rcul
ati
ngblood
vol
ume,and,i
fnecessar
y,opti
mizingperf
us i
onpr ess
ur eandcar
diacf
uncti
onwi
thvasoac
tive
andinot
ropi
csupporttoimprovetis
sueoxy genati
on.

Fl
uidRes
usc
itat
ion

Hypovolemiai
sanimportantfactorc
ontri
buti
ngt oshockandti
ssuehypoxi
a;t
her
efore,
all
pat
ientswithseps
isr
equiresupplement
alfl
uids.Theamountandrateofinf
usi
onaregui
ded
byanas ses
smentofthepatient
svol
umeandc ardiovas
cul
arst
atus.

Monitorpatientsforsi
gnsofv olumeov er
load,s
uchasdy s
pnea,elevatedjugularvenous
pressur
e,cracklesonauscult
ation,andpulmonaryedemaont hec hestradiograph.
Improvement sinmentalstatus,heartr
ate,MAP,capi
ll
aryref
il
l,andUOPi ndic
at eadequat
e
volumeresus c
itati
on.

Volumer esuscitationc anbeac hi

ev edwit
heithercrys t
all
oidorc ol
loids olutions.The
cryst
all
oi dsol
ut i
onsar e0.
9% s odium chl
ori
deandl ac t
atedRingers olution;t hecoll
oid
solut
ionsareal bumi n,dextrans,andpentastarc
h.Al thoughmos tc
linical t
rialshavenots hown
eit
herty peofres us c
itati
onf l
uidtobes uperi
orinsept i
cs hock,amet a-anal ysisbyDelaneyet
alfoundas ignific
antr eductioninmor tal
it
yassoci
at edwi thalbumin-cont ainingsoluti
onsas
compar edwi t
hot herflui
dres usci
tati
onregimens.
[80]

I
tshouldbekepti nmi nd,however,thatcr
y st
all
oidfl
uidsnotonl ymus tbegivenin
c
onsiderabl
y( 2-
4t i
mes )great
ervolumest hancoll
oidfluidsbutals
ot akelongertoac
hiev
ethe
s
ameendpoi nts.Ontheot herhand,coll
oidsoluti
onsar emuc hmor eexpensivet
han
c
ryst
alloi
dsolutions.

The2012Sur vi
vi
ngSepsisCampaignguideli
nesrecommendr apidadminis
trat
ionofanini
ti
al
fl
uidchal
lengewith30mL/kgofc ry
stal
loi
ds ol
ution.[
11]Albumininf
usionshoul
dbeus ed
onlywhens ubst
anti
alamountsofcrys
tall
oidsol
ut i
onarerequi
red.Hydroxyet
hylst
arc
h
sol
uti
onsar enotrec
ommended.
Insomepat i
ents,cl
inicalas
sessmentoft heresponsetovolumeinfus
ionmaybedi f
ficul
t .I
n
suchcases,i
tmaybef acil
it
atedbymoni tori
ngt heres
ponseofCVPorpul monaryart
er y
occl
usi
onpr essure(
PAOP)t ofl
uidboluses.Fl
uidadminis
trati
onshouldbeconti
nuedasl ong
ashemody namicimpr ovementc ont
inues.[
11,60]Hemody namicimprovementi
sdefinedas
i
ncreasedorganperf usi
on,decreasi
ngs er
um lactat
eandmet abol
icaci
dosis
,andimprov edend
-or
ganf uncti
on.

Asustai
nedr i
seofmor ethan5mm Hgi ncar
diacfill
ingpres
sureafteraflui
dvolumeis
i
nfusedindic
atesthatthecompli
anceofthevascularsys
tem isdecr
easingasfurtherf
luidi
s
bei
nginfused.Suchpatient
sar
es us
cepti
blet
ov olumeov erl
oad,andfurtherfl
uidshouldbe
admini
steredwithcare.

Datafrom severalstudiessugges tthatt heinci

denc eofpulmonaryedemai sessent
iall
ythe
samewi t
hc ry
s t
alloidsolutionsaswi thc oll
oidsolut
ionswhenc ar
diacfill
ingpr
essuresare
maint
ainedatal owerl evel.Howev er,ifhigherfil
li
ngpressuresar
er equir
edformaintenance
ofoptimalhemody namics,c r
ystal
loids olut
ionsmayi ncr
easeextr
av ascul
arfl
uidfl
uxesthrough
adecreaseinplasmaonc oticpressure.

EGDTmaybec ons i
deredf orseveres epsisands ept i
cshoc k[68];howev er,thisappr oach
remai nsc ontroversial
,andf urtherstudiesar eunderway .Oneoft hesest udieswasj us t
compl etedandpubl i
shedi n2014,t hePr oCESSt rial,
[57]whi chwasar andomi zedt r
ialof
prot ocol-basedc areforear l
ysept i
cs hock.Thist ri
alenrolled1341pat i
ent sandc ompar eda
prot ocol-basedEGDT( N=439)t otwoot herar ms :protocol-baseds tandar dther apy(N=446)
andus ualcare( N=456).Ther esultsshowednos i
gni fi
cant60- daymor talitydifferencesamong
thet hreear ms ,21%,18. 2%,and18. 9%,r especti
v ely
.Bec ausethes emor tali
t yrateswer elower
thant heor iginalEGDTs t udy,
[68]t heaut horsper formedas ubgroupanal ys
isinc l
udingt he
sickestt hir
dofpat i
entsbas edonl actatelevelsandAPACHEI Iscores,whi chs howeds i
mi l
aror
highermor tali
tythant hatf r
om t heor i
ginalstudy ,
[68]butnobenef i
tfrom EGDTwas
det ectedint hishigh-dis
eas e-severi
typopul ati
on.

Fol
lowingProCESS,twoaddi ti
onal EGDTs tudi
es,onefrom Aus
tral
ia-NewZeal andcall
ed
ARISE[58]andtheotherfrom t heUnitedKingdom cal
ledProMISe,
[59]bothf oundt heexac
t
sameresult
s,sugges
tingt hatstrictpr
otocoli
zedresus
c i
tat
ionfr
om septicshoc ki
snotas
i
mpor t
antasc l
osebeds i
det i
trationofcar
ebas edons oundphysi
ologicpri
nciples,
i
ndependentofmeas uresoflac tateorScv
O2.
Anot hers tudyr ecentlypublished,t heOPTI MISEs tudy ,
[84]wasapr agmati
c ,randomi zed,
obs erver
- blindedt r
ialthatcompar edac ardiacoutput guidedhemody namicther apy
algorithm fori ntr
avenousf luid/inotrope(dopex ami ne)(N=368)withusualcarewi thin6hour s
foll
owi ngmaj orgas tr
ointestinalsurgery(N=366) .Theout c omemeas ur
edwasac ompos i
teof
30-daymor tali
typlusmoder ateormaj orc omplications;noc ompositeoutcomedi f
ferenc es
wer eobs erv edbetweent het wogr oups.Theaut hor salsoper f
ormedanupdat edmet a- anal
ysi
s
witht headdi t
ionoft heirnewdat aandf oundapot ent i
alreducti
oninc omplic
at i
onr ates,but
noti nmor tali
ty.

Howev er
,atthesamet ime,aFrenchstudyshowedt hatinprevi
ouslynonhy pertensivepatient
s,
target
ingameanar teri
alpres
sureof65-75mm Hgwasasgood,i fnotbetter,thant argetinga
meanar t
erial
press
ur e80-85mm Hg. [
78]Inthos epati
entswithpreexi
sti
nghy pertension,
therewaslessAKIandl es
sneedf orhemodial
ysisbutalsomorec ardi
ovascularcompi lati
ons,
presumablybecaus
et hehighermeanar t
eri
alpressuregroupreceiv
edhigherdos esof
vasopres
soragents.

Furt
her,thel
arger et
ros
pecti
vestudyofallofAustral
iaandNewZealandICUc arefr
om 2000-
2012demons tr
atedac l
earpr
ogres s
ivedecli
neinsepti
cshockmort
alit
yratesfrom 35% t
o
18% overthi
speriod,wi
thequaltrendsacrossal
lagegroupsandt
reatments ett
ings.
[47]

Vas
opr
ess
orTher
apy

I
fthepatientdoesnotres
pondtores
usc i
tati
onwi thseverall
it
ers(us
ual
ly4L)ofis
otoni
c
c
rystal
loi
ds ol
uti
onorifevi
denc
eofvolumeov er
loadispresent,t
hedepress
edcardi
ovasc
ular
s
ystem canbes t
imulat
edbymeansofv asopress
ort her
apy .

Vas opr
es s
oradmi nis
trati
onisr equiredforpers i
stenthypotensi
ononc eadequateintravas
cular
volumeex pansionhasbeenac hieved.Persist
enthy potensi
onistypic
all
ydef i
nedass y
stol
ic
bloodpr essur
el owerthan90mm HgorMAPl owerthan65mm Hgwi t
halteredtis
sue
perfusi
on.Themeanbl oodpres s ur
er equir
edf oradequatesplanchni
candr enalperfusi
on
(MAP, 60or65mm Hg)i sbasedonc lini
cali
ndi c
esofor ganfuncti
on.

Thegoalofvasopr
essort
herapyi
storev
ersethepathol
ogi
cv as
odil
ati
onandal
teredblood
fl
owdist
ributi
onthatocc
urasaresul
toftheact
ivat
ionofadenosi
netri
phos
phate(ATP)-
dependentpotass
ium c
hannel
sinv
asc
ulars
moot
hmus
clec
ell
sandt
hes
ynt
hes
isoft
he
vasodi
lat
ornit
ricoxi
de(NO).

Fi
rst
-li
neagent
s:nor
epi
nephr
inev
sdopami
ne

Therecommendedf ir
st-li
neagentf ors epti
cs hockisnorepinephri
ne,prefer
ablyadmini
stered
thr
oughac entralcatheter.[11,60]Nor epi
nephrinehaspr edominantalpha-r
eceptoragonis
t
eff
ectsandr es
ultsinpot entper i
pheralart
er i
alvasocons
tr i
cti
onwi t
houtsignif
icant
ly
i
ncreasingheartrateorc ardiacoutput.Thedos agerangef ornorepinephr
ineis5-20g/min,
anditisnotbasedont hewei ghtofthepat ient.

Norepi
nephrineispreferr
edtodopamineformanagi
ngs ept i
cshockbecausedopamineis
knownt ocauseunfavorablef
lowdi
str
ibut
ion(morearr
hy thmias)
.Inthi
ss et
ting,
norepi
nephrinehasbeens howntobeboths i
gni
fi
cantl
ys aferandsomewhatmor eef
fec
tiv
e.

Inas y
stemati
crevi
ewofr andomi z
edc ontroll
edt ri
als
,norepi
nephr i
newass i
gnifi
cantly
superi
ortodopaminei nimpr ovi
ngbot hin-hos pit
aland28-daymor talit
yi ns ept
icshock
pati
ents.
[85]Inamet a-analy
s i
sthatevaluatedt hese2agentsint hes et
tingofs epticshock,
theinvest
igat
orsdeterminedt hatincompar is
onwi t
hdopami ne,epinephr i
newasas soci
ated
withadec r
easedri
skofdeat handal oweri ncidenceofarrhyt
hmi cev ents.[86]

Intheor y,norepi
nephr i
nei
st heidealv
asopressori
nt hes et
tingofwar mshock,wher ei
n
peripheralv as
odi
lationexi
stsinassoci
ati
onwi thnor malorincreasedcar
diacout
put .The
typicalpatientwi
t hwarms hockhaswar m ext
remitiesbutex hi
bitssys
temichypotens i
onand
tachy c
ardia,theresult
sofdec r
easedsystemicvascularresi
stance.

Dopami neshouldbeusedonlyincer
tainhighlyspeci
fi
cs i
tuati
ons,suchaswhent hereisalow
ri
skoft achy
arrhyt
hmiasandinthepresenceofc oexi
stentbradycar
dia.Treatmentusual
ly
beginsat5-10g/kg/minIV,andtheinfus
ioni sadj
ustedaccordi
ngt ot hebl
oodpressureand
otherhemody namicpar
ameters.Oft
en,patientsmayrequirehighdos agesofdopamine(upto
20g/ kg/min)
.Low-dosedopamineisnotr ecommendedf orrenalprotecti
on.[
11,60]

Sec
ond-
li
neagent
s
Second-l
inevas
opres
sor
sappropr
iat
eforpati
ent
swhohavepersi
stenthypotens
iondes
pit
e
maximaldosesofnor
epi
nephr
ineordopaminear
eepi
nephr
ine,phenyl
ephri
ne,and
vas
opressin.

Epinephr i
nec l
earl
yincreasesMAPi npati
entsunresponsivetoothervasopress
ors,mainl
yby
vi
rtueofi tspotentinot
r opiceff
ec t
sont heheart
;thus,itshoul
dpr obablybethefir
st
al
ternat i
veagentc onsi
deredi npatient
swithsepticshockwhos howapoorc li
nic
alres
pons e
tonor epinephri
neordopami ne.
[11,60]Adv er
seeffectsincl
udetachyarrhyt
hmias,myocardi
al
ands planchnicis
chemia,andi ncreasedsyst
emiclactateconcent
r at
ions.

Phenylephri
neexertsapurealpha-recept
oragonistef
fect
,whi c
hr es
ultsi
npotent
vasoconstr
ict
ion,al
beitattheexpenseofdepressedmy oc
ardialcontr
acti
li
tyandhear
trat
e.
Phenylephri
nemaybec onsi
deredaf i
rst-
li
neagentinpati
entswi t
hex t
remetachyc
ardi
a;i
ts
purealpha-r
eceptoracti
vit
ywillnotresul
tini
ncreasedchronotropy.
[87]

Vasopressin,oranti
diureti
chor mone( ADH) ,hasbeenpr opos edforuseinseptics hock
becauseitisanendogenouspept idewi thpotentv as
oactiveef f
ectsanditscir
culatinglevel
s
aredepress edinsepti
cs hock.Accordi
ngt othe2012Sur v i
vi
ngSeps i
sCampaigngui del
ines,
vasopressi
ns houldnotbet hes i
ngleiniti
alvasopressorbuts houldber es
ervedfors al
vage
therapy.
[11]Af terf
irs
t-li
net r
eatment ,0.03U/ minofvasopr essi
nmaybeaddedt o
norepinephr i
ne,wit
hanant ici
patedeff ectequival
enttot hatofnor epi
nephri
neal one.[11,60]

Char
act
eri
sti
csoft
hev
asopr
ess
ors

Nor
epi
nephr
ine

Nor epinephr i
neisapot entalpha- adr
energi
cagonistwit
hmi ni
malbet
a-adrenergi
cagonist
eff
ec ts.Itcanincreasebl oodpr essur
esuccess
ful
lyinpati
entswit
hsepsiswhor emain
hypot ensiveafterfl
uidr esus
c i
tationanddopamine.Thedosagemayrangef r
om 0.2to1.5
g/kg/ min,anddos agesashi ghas3. 3g/kg/
minhav ebeenusedbecauseofthealpha-
recept ordownr egul
at i
oni nseps i
s.
Inpatientswithsepsis
,indicesofr egionalperfusion( eg,urinefl
ow)andl actat
econcentrat
ion
haveimpr ovedafternorepinephr i
neinfusion.Sev eralstudieshavefoundt hatasi
gnifi
cantl
y
greaterpercentageofpatient str
eatedwi thnor epinephr i
newer eresusci
tatedsucces
sful
ly,i
n
compar is
onwi thpati
entst reatedwithdopami ne.[85,86]Ther efor
e,norepinephr
ineshouldbe
usedear l
yands houldnotbewi thheldasal astres ortinpat i
entswithsevereseps
iswhoar ein
shock.

Concernsaboutc ompr
omisi
ngs pl
anc
hnictissueoxygenati
onhavenotbeenborneoutbythe
dat
a;thestudieshaveconf
irmednodelet
eriouseffect
sons pl
anchnicox
ygenconsumpti
on
andhepaticgl
uc osepr
oducti
on,pr
ovi
dedt hatadequatecardi
acoutputi
smaint
ained.

Dopami
ne

Aprec ursorofnorepinephri
neandepi nephri
ne,dopaminehasv aryi
ngeffects
,accordi
ngto
thedos esinfus
ed.Atl owerdoses,i
thasamuc hgreateref
fectonbet ar
ec ept
ors;athi
gher
doses,ithasmor ealpha-rec
eptoreffectsandincr
easesperi
pher alv
asoconstri
cti
on.

Dos agesrangef rom 2to20g/ kg/ min.Ados agelowerthan5g/ kg/minr esult

si n
vasodilat
ionofr enal,mes enter
ic,andc oronarybeds.
[11]Atados ageof5- 10g/ kg/mi
n,
beta1- adrenergiceffec
t sinduceani ncreaseincardi
accontract
il
ityandhear trate.Atdosages
ofabout10g/ kg/min,alpha-adrenergiceffect
sleadtoarteri
alvasocons
trictionand
elevati
oni nbloodpr essure.[
11]

Dopami neisoftenef f
ec t
iveforres t
oringmeanar ter
ialpres sur
einpatientswithsepticshoc k
whor emainhy potensiveaftervolumer esusci
tati
on.Thebl oodpr essur
ei ncr
easesprimarilyas
aresultofthedr ugsi
not r
opiceffec t
,whi c
hisusefulinpatientswhohav econcomitant
reducti
onsinc ardiacfuncti
on.Howev er,asmentionedabov e,i
nac ompar i
sonof
norepinephri
net odopami nef orthemanagementofar t
erialpressurei
ns epti
cs hock,fai
lure
ofdopami netor eachmeanar ter
ialpressuretar
getsoc curredin30% oft hetreatmentarm,
necessit
ati
ngaddi ngnor epinephrine.

Dopaminemaybepar t
icular
lyuseful
int hesett
ingofc ol
ds hock,wher
eperipheral
vas
oconstr
ict
ionexi
sts(coldextr
emities)andcardiacoutputistool
owt omaintainti
ssue
per
fusi
on.Undesi
rabl
eef fect
sincl
udet achycar
dia,inc
reasedpulmonaryshunti
ng,the
potenti
alt
odecr
eas
espl
anc
hni
cper
fus
ion,andani
ncr
eas
einpul
monar
yar
ter
ialwedge
pressur
e(PAWP)
.

Low- dose(renal-dose)dopami nehasbeens tudied.Dopamineatadosageof2-3g/kg/mini

s
knownt oini
tiatediuresisbyincr
easi
ngr enalbloodflowinhealt
hyani
malsandv ol
unteer
s;
howev er,severalwell
- desi
gnedcli
nicalt
rial
shav enotfoundsuchregi
menst ohaveany
benef i
ci
aleffectsonr enalbloodflowandf unctioninthesett
ingofci
rcul
ator
yshockofany
eti
ology .

Multi
plestudi
esal
sohav
enotshownpr ophylact
icorther
apeuti
clow-dos
edopami ne
administ
rati
ontohav
eanybenef
ici
alef
f ecti
npat i
ent
swi t
hsepsiswhoarecri
ti
call
yil
l.I
nvi
ew
oftherealsi
deeff
ect
sofdopami
neinfus i
on,theuseofrenal
-dosedopamineshouldbe
abandoned.

Epi
nephr
ine

Epi
nephrinecani ncr
easeMAPbyi ncr
easingcardiacindexandstrokevol
ume,aswellasby
i
ncreasi
ngs ys
t emicvasc
ularr
es i
stanceandhear trat
e.Thisagentmayincreas
eox y
gen
del
iver
yandox ygenconsumpti
on.Theus eofepi nephrinei
srecommendedonl yi
npat i
ent
s
whoareunr esponsiv
etot r
adi
tionalagents.Theundes ir
abl
eeffectsofepi
nephri
neincl
udethe
fol
lowi
ng:

Ani
ncr
eas
eins
yst
emi
candr
egi
onall
act
atec
onc
ent
rat
ions

Thepot
ent
ialt
opr
oduc
emy
ocar
diali
schemi
aandpr
omot
edev
elopmentofar
rhy
thmi
as

Reduc
eds
planc
hni
cfl
ow

Pheny
lephr
ine

Pheny l
ephri
neisasel
ectiv
ealpha1- adrenergi
creceptoragonistt
hatisusedpr i
maril
yin
anesthesiat
oincr
easebloodpressure.Althoughthedat aareli
mited,st
udieshavefound
phenylephri
netoincr
easeMAPi npat i
entswhower esepti
candhy potensi
v ewit
hincreas
ed
oxygenc onsumpt
ion.However,conc ernremainsaboutthisagent
spotential
toreducecardi
ac
outputandlowerheartratei
npat i
ent swithsepsi
s.Phenylephr
inemaybeagoodc hoicewhen
t
achy
arr
hyt
hmi
asl
imi
tther
apywi
thot
heragent
s.

Vas
opr
ess
in

Vasopressini
ss y
nt hesi
zedinthehypothalamusandex c
retedbythepos teri
orpitui
tary.I
n
contrasttoendogenousc atec
holamines(eg,norepinephri
ne),whos
es erum level
sare
univ
er s
all
yhighins epti
cshock,vasopres
sinstoresarelimitedandi
tslevelsarelow.[88]
Furthermore,cat
ec hol
amineeffect
ivenessonv ascul
arsmoot hmusclecellsi
sinhibi
tedbyt he
acti
vationofATP- dependentpotassi
um channelsandNO.

Exogenousadmi nistr
ati
onofv asopressinresultsinvasoc onstrictionv iaactiv
ati
onofV1
receptorsonv ascularsmoothmus clecellsthathav etheef fectofi nhi biti
ngATP- dependent
potassium channelsand,intheory,restori
ngt heef f
ecti
v enes sofc at echolamines.Vasopres
sin
i
sal sothoughtt oinhibi
tNOs y
nthas eandt hereforecount erac tthev as odi
lator
yeffectofNO.
Inaddition,vasopressi
nincreasesrenalperfusionbyc aus i
ngv asodi lationofaf f
erentrenal
art
erioles,i
nc ontrasttotherenalvasocons tr
icti
onc ausedbyc atec hol amines.

Severalsmallclini
c altri
alshaveshownt hatlow- dosevasopress i
nincr
easesMAPand
decreasesther equi r
ementf orcatecholami neswhi l
emai ntai
ningmes enter
icandr enal
perfusi
on.[88]Howev er
,alarge,randomi zedt r
ial(t
heVas opres si
nandSept i
cShoc kTri
al
[VASST] )didnotf indmor t
ali
tytobes ignific
ant l
ylowerinpat ientswhoreceivedvasopres
sin
i
naddi ti
ont onor epinephr i
nethani nthos ewhor ecei
vednor epinephr
inealone,ev
ent hough
vasopressinreduc edt herequir
ementf ornor epinephrine.[
89]

Overall
,themaj oradv erseeffect
sat tri
but edtovasopr
essin(my ocardi
ali
schemia,cardiac
arr
est,mes enteri
c,anddi git
alischemi a)wer enotsi
gni
ficantl
yincreasedi
nt hetri
al;howev er
,
pati
entswit hknownc oronaryarterydi seaseorcongest
iveheartfail
urewereexc l
udedf rom
thestudy.[
89]Thei nc idenceofdigitalischemiawashigherwi t
hv asopres
sinuse.Bec ausethe
meant imet oreceiv
ingt hedr uginVASSTwas12hour s,thisstudydoesnotaddr esst heuseof
vasopressi
ni nearl
ys eps i
sresuscit
ation.

I
not
ropi
cTher
apyandAugment
edOx
ygenDel
iv
ery

Alt
houghmy oc
ardialper
for
manceisal
tereddur
ingsepsi
sands epti
cshoc
k,car
diacoutput
gener
all
yismaint
ainedinpati
ent
swithvolume-
resus
cit
atedsepsis
.Datafr
om the1980sand
1990ssuggest
edali
nearrel
ati
onbetweenoxygendel
iv
eryandoxygencons
umpti
on
(pat
hol
ogicsuppl
ydependency)
,indi
cat
ingt
hattheoxygendel
iv
eryli
kel
ywasi
nsuf
fic
ientt
o
meetthemetabol
icneedsofthepati
ent.

Howev er,subsequentinv
es ti
gati
onsc hal
lengedthec onceptofpat hologicsupplydependency,
suggestingthatelevat
ingc ar
diacindexandox ygendeliver
y( hyper
r esusci
tati
on)wasnot
associ
atedwi thimprovedpat i
entoutcome.Ther efor
e,ther oleofi
not ropicther
apyi s
uncert
ain,unlessthepatienthasinadequatec ar
diacindex,MAP,mi xedvenousox ygen
satur
ation(Smv O2),andUOPdes pit
eadequat evolumer esuscit
ati
onandv asopressorther
apy
.

Pati
entswi t
hs everesepsisorsepticshockhav ehypermetabol i
sm,mal dis
t r
ibuti
onofblood
fl
ow,and,pos sibl
y,suboptimalox ygendel
ivery;t
herefore,attempt satdetec t
ingand
correct
ingtiss
uehy poxiamus tbemade.Lac ticaci
dos i
sisani ndicati
onofei thergl
obal
i
schemi a(i
nadequat eoxygendel i
very)orr
egional(organ-specifi
c)ischemia.Calcul
ati
onofpH
i
nt hegas t
ricmuc osaviagastr
ictonomet r
ymaydet ecttissuehy poxi
ai nthes pl
anchni
c
ci
rculat
ion;howev er,t
histechniquehasnotbeenv al
idatedex tensi
velyandi snotwidely
avail
able.

Dobutamineisaninotr
opicagentthatsti
mulat
esbetar ec
eptor sandresultsi
nincreas
ed
car
diacoutput.I
ntheory,i
tcanenhancetiss
ueoxygendel i
veryinpat i
entswithsepti
cshoc k
whohaver ecei
vedadequatefl
uidr
es us
cit
ati
onandv asopress
ors uppor t
.InEGDT,dobut amine
i
srecommendedi fthereisevi
denc
eoft is
suehypoperf
us i
on(c entralv
enousox ygensaturat
ion
[Sc
vO2]<70mm Hg)af terCVP,MAP,andhemat ocri
tgoalshav ebeenmet .

The2012Survi
vi
ngSepsisCampaignguideli
nesrecommendadmi ni
str
ationofdobutamine
dosagesupto20g/kg/
mi nonlyi
nt hepresenceofmyocar
dialdys
functionorper
sist
ent
hypoperf
usi
ondespi
teadequatefl
uidresusc
itat
ionandadequateMAP.[11]

Althoughi nit
ialaggres
s i
veresus ci
tat
iont omax i
mizeox ygendeli
v eryimpr ov
esout come,
mani pulati
onofox y
gendel i
verytodel i
vers upraphysiologicoxygent otis
suesv iablood
transfusion,fl
uidboluses,orinotropictherapyonc eor gandy sfunc ti
onhasdev elopedhasnot
i
mpr ov edout comei ncri
ti
call
yi l
lpati
ents.Hay esetalr epor t
edahi ghermor tali
tyinpatient
s
withs epsiswhower emaintai
nedonhi ghlev el
sofox y gendelivery.[90]Thus,inot r
opic
therapyi snotr ec
ommendedf ori
nc r
easingt hec ar
diaci ndextos upr anormallevels.
[11,60]
Inpatientswiths epticshoc k,theinabil
it
ytoincreaseoxygenc onsumptionandtodec r
ease
l
actatelevelsmos tlikelyisac onsequenceofimpai r
edox ygenex t
ract
ionorinabi
li
tytorever
se
anaerobicmet abolis
m.Boos ti
ngox ygendeli
verytos upr
anor mall
evel
sdoesnotr ever
sethese
pathophy si
ologicmec hanis
msaf t
ert hedev
elopmentofor ganinj
ury.

Empi
ri
cAnt
imi
crobi
alTher
apy

Empiri
cantimicr
obialtherapys
houldbeini
ti
atedearl
yinpati
entsexper
ienci
ngsept
ics
hoc
k
(wi
thi
n1hourofr ecognit
ionofsept
icshoc
k)ands ev
eresepsi
swithoutsept
ics
hock,i
f
possi
ble.
[11,60]

TheSurvivi
ngSeps i
sCampai gngui deli
nesrecommendi nc
ludi
ng1ormor eagentsthatar
enot
onlyact
iveagainsttheli
kelyorganismsbutal socapabl
eofpenetrati
ngi
nadequat e
concentr
ationsint
ot hepresumeds ourceofsepsi
s,wi
thdail
yreeval
uat
ionoft heanti
-
i
nfecti
vetherapyforpotentialde-escalat
ion.
[11,60]

General
ly,a7-t o10- daytr
eatmentcourseisf ol
lowed.Longertreat
mentr egimensmaybe
warrant
edi nt hepr esenceofas l
owc l
ini
calresponse,undrai
nablefociofinf
ec t
ion,and
i
mmunol ogicdef i
ciencies(
eg,neutr
openia).Theus eofprocalc
itoni
nors i
milarbiomarkersmay
fac
il
itat
edisc ont i
nuanc eofanti
biot
icsinpatientswithcl
inic
alimprovementandnof urther
evi
denceofi nf ect
ion.[11]

Combi
nat
ionempi
ri
cther
apyi
srec
ommendedf
orpat
ient
swi
tht
hef
oll
owi
ng[
11]:

Dif
fic
ult
-to-
treat
,mul
ti
drug-
res
ist
antmi
croor
gani
sms(
eg,Ps
eudomonasandAc
inet
obac
ter
spp)

Sev
erei
nfec
tionsas
soc
iat
edwi
thr
espi
rat
oryf
ail
ureands
ept
ics
hoc
k

Sept
ics
hoc
kandbac
ter
emi
afr
om pneumoc
occ
i

Howev er
,combi nati
ont herapyshoul
dbeli
mitedto3-5day
s,af
terwhichper
iodtr
eatment
shouldswitc
htot hemos tappropri
atemonot
herapyoncet
heresul
tsofthesus
cepti
bil
it
y
profi
leareavai
lable.
[11,60]

Thef
oll
owi
ngpoi
ntsmus
tal
way
sbec
ons
ider
ed:
Ear
lybr
oad-
s pect
rum empir
icanti
biot
icther
apyi
sessent
ial
;thec
over
ages
pec
trum wi
llbe
nar
rowedl
ater,whencult
ureresul
tsbecomeavai
labl
e

Wai
ti
ngunt
ilc
ult
uresar
ebac
kisani
nval
idr
eas
ont
owi
thhol
dant
ibi
oti
cs

Onl
y30% ofpat
ient
swi
thpr
esumeds
ept
ics
hoc
khav
epos
iti
vebl
oodc
ult
ures[
3,4,5,37]

About25% ofpr
esumeds epti
cshockpat
ient
sremaincul
tur
e-negativ
efrom al
lsi
tes
,but
mortal
it
yissi
mil
artothatforcul
tur
e-posi
ti
vecount
erpar
ts[3,4,5,37]

Pr
omptlydisc
onti
nueanti
microbi
alt
her
apyi
fthepat
ient
sc
ondi
ti
oni
sdet
ermi
nedt
obef
rom
anoni
nfect
iouss
ource[11,60]

Ant
ibi
oti
csel
ect
ion

Thes el
ec t
ionofappropri
ateagentsisbasedont hepatient
sunderlyi
nghos tdefenses,t
he
potentialsourcesofi
nfec
tion,andthemos tli
kel
yc ulpr
itorganisms.Ant
ibi
ot i
csmus tbebroad
-spectrum agentsandmus tcovergram-posi
ti
ve,gram- negati
ve,andanaerobicbac t
eri
a
becauseor ganismsfr
om anyoft hes
ediffer
entclassesc anproducethesamec li
nicalpi
ctur
eof
di
s t
ributiv
es hock.

Ift
hepatientis
ant i
bioti
c-exper
ienced,
st
rongconsi
derat
ionshouldbegiventousingan
aminogl
ycosiderat
hert hanaquinoloneorcephal
ospor
inforgram-negat
ivecover
age.
Knowingtheantibi
ot i
cresist
ancepatter
nsofboththehospit
alit
sel
fanditsref
erralbas
e(i
e,
nursi
nghomes )i
sv eryimportant.

Ant i
bioti
csshoul
dbeadmi ni
steredparenter
all
y,indos
esadequatet
oac hiev
ebacter
ici
dal
serum level
s.Manyst
udieshavef oundthatcli
nic
ali
mprovementcorr
elateswit
hthe
achievementofserum bac
teri
cidallev
elsrat
herthanwiththenumberofantibi
oti
csgiv
en.

Intheselectionofempir i
canti
bioti
cs,theincreasi
ngpr evalenceofMRSAmus tbet akeninto
account,andanagents uchasvancomy c
inorlinez
olidshoul dbeincluded.Thisisespeciall
y
trueinpatientswithahistor
yofI Vdrugus e,thosewi t
hi ndwell
ingvas c
ularcathetersor
devic
es,ort hosewithrecenthospital
izati
ons.Antianaerobiccoverageisindi
c atedinpatients
withint
ra-abdomi nalorperi
nealinf
ec t
ions.
Certai
norganisms,chiefl
yEnt er
obac t
eri
aceae( eg,Escheric
hiac ol
iandKl ebs i
ell
apneumoniae)
,
contai
nabet a-l
actamas eenzymet hathydroly
z esthebet a-l
actam ringofpeni ci
lli
nsand
cephalos
porinsandthusi nacti
vatestheseantibioti
cs(ESBL- producingbac teri
a).Thi
s
phenomenonhasbec omeani ncr
easingconcer nasitsprevalencehasi ncreased.Beta-l
act
am
anti
bioti
csthathaveremai nedeffecti
veagainstESBL- produc i
ngor ganis
msi ncl
ude
cephamy ci
ns(eg,cef
ot etan)andcarbapenems( eg,imipenem,mer openem,and
ert
apenem) .
[91]

Inimmunoc ompet entpat i

ents,monot her
apywi thc ar
bapenems( eg,imipenem and
meropenem) ,third-orf ourth-generat
ionc ephalos
por i
ns(eg,cefot
ax i
me,c ef
operazone,
ceft
azidime,andc efepime),orextended-spectrum penici
ll
ins(
eg,ticar
c i
ll
inandpiperaci
ll
in)i
s
usual
lyadequat e,wit houttheneedf oranephr otoxicaminogly
c osi
de.[92]Pati
entswhoar e
i
mmunoc ompr omi sedorathi ghr i
skformul ti
drug-resi
stantorganis
mst ypi
cal
lyrequir
edual
broad-spectr
um ant ibi
oti
cswi thoverl
appingc overage.

Withi
nthes
egener
algui
del
ines
,nos
ingl
ecombi
nat
ionofant
ibi
oti
csi
scl
ear
lys
uper
iort
oany
ot
her.

TheFDAr ecentlyappr oved3newant i

biot
ics,oritavanc i
n( Orbac ti
v),dal
bavanc i
n(Dal vance)
,
andtedizoli
d( Si
v extro),forthet r
eatmentofac utebac teri
als ki
nands ki
ns tr
uc t
ureinf ect
ions.
Theseagent sareac t
iveagai nstStaphy l
ococcusaur eus( i
ncludingmet hi
cil
li
n-susceptibleand
methici
ll
in-resis
tantSaur eus[MSSA,MRSA]i solates )
,Strept ococcuspy ogenes,
Str
eptococ cusagal acti
ae,andSt r
ept ococcusangi nos usgr oup( i
nc l
udesSt r
eptococ cus
angi
nosus ,Streptoc occusi nter
medi us,andSt reptoc occusc ons tel
latus)
,amongot hers.For
completedr uginf ormat i
on,includingdos i
ng,s eet hef oll
owi ngmonogr aphs:

Or
itav
anc
in

Dal
bav
anc
in

Tedi
zol
id

Communi
ty-
acqui
redpneumoni
a

Forinpati
entswi
thpneumoniawhoar
enotadmi tt
edtotheI
CU,theguidel
inesf
ormulat
edby
theInfec
tiousDi
seas
esSoci
etyofAmeri
ca(IDSA)andtheAmer
icanThoraci
cSociet
y(ATS)
recommendadmi ni
ster
ingt
hefol
lowi
ng[66]:
Ar
espi
rat
oryf
luor
oqui
nol
one,es
pec
ial
lyi
npeni
ci
ll
in-
all
ergi
cpat
ient
s

Abeta-
lact
am agent(
cef
otaxi
me,cef
tri
axone,orampi
ci
ll
in)pl
usamacroli
de;er
tapenem may
beus
edf orsel
ect
edpati
ents
,anddoxycycl
inemaybeanalter
nat
ivet
ot hemacrol
ide

Anti
biot
ictherapyforamini
mum of5day sforcommuni t
y-ac
quiredpneumonia;t
he
tr
eatmentdurationmaybeincreas
edincomplicat
edc as
esorinc as
eswheretheinit
ialt
her
apy
di
dnotpr ovi
deac li
nic
alr
esponseagai
nsttheidenti
fi
edorganis
m

Fori
npati
entswi
thpneumoni
awhoareadmit
tedt
otheI
CU,t
heI
DSA/
ATSgui
del
inesof
fer
thef
oll
owingmini
malrec
ommendat
ions[
66]:

Administ
erabeta-l
act
am ( eg,cefot
axime,ceft
riaxone,ampi
cil
li
n-s
ulbactam)pl
usei
ther
azi
thromyci
noraf l
uoroquinolone;penic
il
li
n-al
lergicpati
ent
smayr ecei
vearespi
rat
ory
fl
uoroqui
noloneandaztreonam

Forpseudomonali nf ecti
ons,admi nis
ter(1)anant i
pneumoc occ
al,anti
pseudomonalbet
a-
l
actam agent( eg,pi peraci
ll
in-taz
obac tam,cefepime,i
mi penem,ormer openem)plus
ci
proflox
ac i
norl ev ofloxaci
n;(2)thebet a-l
act
am abov eplusanami nogly
cosideand
azi
thromy ci
n;or( 3)t hebeta- l
actam aboveplusanami noglycosi
deandanant i
pneumoc
occal
fl
uoroquinolone(f orpeni ci
ll
in-al
lergi
cpatient
s ,useaztr
eonam insteadoftheabovebet
a-
l
actam)

Addvancomy
cinorl
inez
oli
dforpat
ient
swi
thc
ommuni
ty-
acqui
redMRSA(
CA-
MRSA)
i
nfec
tion

Ot
herI
DSA/
ATSr
ecommendat
ionsi
ncl
udet
hef
oll
owi
ng[
2]:

Inf
luenzaAEar l
ytreat
ment(
48hraf t
ersy
mpt omsonset
)withosel
tamivi
rorzanamivi
r;
alt
hought hese2agentsar
enotrecommendedforusei
nunc ompl
ic
atedinfl
uenzawit
h
symptomsl ongert
han48hours,theymaybeus
edf orr
educti
onofvir
alsheddi
ngininpati
ent
s
orforinfl
uenzapneumonia

H5N1infecti
onI
ns uspectedcas
es,admini
sterosel
tami
vi
randant ibac
teri
alagentsagai
nstS
pneumoniaeandSaureus,whic
hc ancaus
esec ondar
ybacter
ialpneumoniaininf
luenza
pati
ent
s

I
ntr
a-abdomi
nali
nfec
tions
Forcommunity-acqui
redabdomi nal i
nfect
ions,theIDSAandt heSurgi
calI
nfect
ionSoci
ety
(SI
S)indi
cat
ethatempi r
icantibi
otictherapiesshouldbeacti
veagainstent
eri
cgram-negat
ive
aerobi
candfacult
ativ
ebacil
liaswel lasenteri
cgr am-pos
iti
vestrept
ococci
.[
2]

Empiriccoverageisnotneededf orEnt erococ cus,norisempi r

icanti
fungaltherapyneededf or
Candida,unlesstheseinfectionsar esev ere.Ant i
bioti
cswi thacti
vi
tyagainstEf aecal
isinc l
ude
ampicil
li
n,piperaci
lli
n-tazobactam,andv anc omyc i
n.Fl
uc onazol
eisusedf orisolat
edCal bi
cans;
anechinocandin(eg,c aspofungin,mic afungi n,oranidulafungi
n)isusedforfluconazole-
resi
stantCandida.[2]Inc r
iti
call
yillpatient s,anec hi
nocandi ni
srecommendedov eratriazole
(eg,f
luconazoleoritraconazole).
[2]

Agentsthatcausehealt
hcare-
assoc
iat
edintr
a-abdominali
nfec
tionsincl
udeCandi
da,
Enter
ococ c
us,andMRSA.Empi ri
canti
biot
icther
apyforthosei
nf ec
tionsshoul
dbebasedon
l
ocalsuscepti
bil
it
yresul
ts.

Inadult
swi thcommuni t
y-acquiredinfect
ionorhos pi
tal-as
sociatedintr
a-abdominalinf
ecti
on
ofhighs ev
erit
y(eg,AcutePhy siol
ogyAndChr onicHeal thEval
uat i
on[APACHE]I Is c
ore>15),
broad-spectr
um agentsareus edagainstgram-negativeacti
vit
y( eg,metroni
dazoleplus
meropenem,i mipenem-ci
las
t ati
n,doripenem,piperaci
ll
in-t
azobac tam,ci
profl
oxacin,or
l
evofloxaci
n;alt
ernati
vel
y,met roni
dazoleplusceftazi
dimeorc efepime).
[2]

Antibioti
cst hatarenotrecommendedf ortr
eati
ngi ntra-
abdomi nali
nfecti
ons,becauseoft he
greaterprevalenceofr es
istance,i
ncludeampici
ll
in-sul
bactam andquinolones(highresi
stance
i
nc ommuni ty-acquir
edEc oli
),aswellascef
otetanandc li
ndamy ci
n(highresist
ancein
Bacteroidesf r
agili
s).
[2]I
naddi ti
on,aminogl
ycosides,becauseoftheirtoxi
cit
yandt he
avail
abil
ityofot heragents,arenotrecommendedf orrouti
neus eincommuni ty-
acquir
ed
abdomi nalinfecti
ons .

Cor
tic
ost
eroi
dTher
apy

Cort
icosteroidinsuff
ici
enc yhasbeenas soci
atedwithsevereil
lness.[
93]TheAmer i
canCol l
ege
ofCri
ticalCareMedi ci
ne( ACCCM)us esthet er
m cri
ti
calil
lnes
s -
relat
edc ort
icoster
oid
i
nsuffi
ci
enc y(CIRCI)todes cr
ibehypothalamic-pi
tui
tary
-adrenal(HPA)ax i
sdy sf
unctionin
cr
iti
cal
lyillpati
entsandr ecommendsav oidi
ngus eoftheterms absolut
eor r
elat
iveadrenal
i
nsuffi
ci
enc yins uchpatients.
[65]
Alt
hought hereistheor
etic
alandex perimentalanimalevidencefav
or i
ngtheuseoflargedoses
ofcor
t i
costeroi
ds(eg,methylprednis
olone,hy dr
ocort
isone,anddex amet
hasone)i
npat i
ents
wit
hs ever
es epsi
sands epti
cs hock,thecl
inicalmedicall
iter
atur
edoesnots uppor
tt herout
ine
useofsuchdos esinthesepatients.

High-dos ecor t
icosteroidss houldnotbeus edinpatientswi t
hsev eresepsisorsepticshock.A
meta-analy si
sofpr os pecti
v e,randomized,contr
oll
edt r
ialsofglucocorti
coidusedi dnotf i
nd
anybenef itfrom cort i
costeroidsands uggestedthattheirusecoul dbehar mful
.[94]Ar evi
ew
of3met a-analysesfoundt hatus eoflow-dosecorti
costeroidsdidnoti mprovesur v
ivalin
septi
cs hoc kands ev ereseps i
sandt hattheywer eassoci
at edwiths i
deeffectst
hati ncl
uded
superi
nf ecti
ons ,bl
eedi ng,andhy per
glycemia.
[95]

Somet r
ial
shavedocumentedposi
tiv
er esul
tsfrom s
tress
-doseadmi ni
str
ati
onof
cort
icos
teroi
dsinpati
ent
swithsevereandrefract
oryshock.[
96]Althoughfurt
her
confi
rmatoryst
udi
esareawait
ed,str
ess -
dosesteroi
dc ov
erageshouldbeprovidedt
opat
ient
s
whohav etheposs
ibi
li
tyofadr
enalsuppressi
on.

Others t
udieshav eshownt hatl
ower-dosest
eroidsmaybebenef i
c i
alforpati
entswi
threl
ati
ve
adrenalinsuffi
ci
enc y
.Inas tudybyAnnaneetalt hati
ncluded299pat i
entswithsept
ics
hock
whower er andoml yassignedtorecei
velow-dosester
oids( hydr
oc ort
isone,50mgq6hr,and
fl
udrocor t
isone,50g/ day)orplac
ebo,77% werenonres ponders;fornonresponder
swho
recei
veds teroi
ds,therewasa10% abs ol
utebenefi
twithr espec
tt omor tal
it
y(63% v
s
53%) .
[97]

Inthisstudy ,al
lpati
ent shadbeeni ntubated,hadbeenpersis
t entl
yhy potensivedes pi
te
cry
s t
all
oidr esusci
tationandv asopressoradmi ni
str
ati
on,andhadhadev i
denc eofend- organ
fai
lur
e.[97]Nonr esponder swer edefi
nedast hos
ewhos ecort
is oll
evelincreasedbyl essthan
10g/ dLinac ort
isolstimulati
ontestandt huswer econsi
deredadr enall
yinsuffic
ient.This
testi
nv ol
vesmeas uringcortis
ollevel
sbefor eand30mi nut
esaf terIVadmi nis
t r
ationof0.25
mgofc osynt r
opin(ie,adrenocorti
cotropi
chor mone[ACTH] )
.

Alt
houghperformi
ngthec or
tisolst
imul
ati
ont es
tintheEDs et
tingmaynotbeprac
tic
al,gi
ven
ti
meandr es
ourceconst
raint
s,itiswort
hnotingthatmorethan75% ofpati
entswi
th
vasopr
ess
or-ref
rac
toryhypotensionwereadr
enallyi
nsuf
fic
ient
.[97]Thi
sfi
ndi
ngsuggest
ed
thatthemaj or
ityofpatient
swithvasopres
sor-r
efr
actor
ys hockwouldbenefi
tfr
om s
ter
oid
administ
rati
on,r egar
dlessoft
heresult
soft hecor
tis
olsti
mulati
ontest
.Ac ommonchoicei
s
hydrocort
isone100mgI V;agoodalter
nativei
sdexamethasone10mgI V.

I
nas ubs equents t
udy,Annaneetalpubl i
shedas yst
emat i
crevi
ewofc or
tic
osteroidusefor
s
everes epsisands epticshock,thepooledresult
sofwhi chshowedthatthesubgr oupof
s
tudi
esus i
ngpr olonged,low-dos ecorti
cost
eroidtherapydemonstr
atedabeneficialef
fecton
s
hort-term mor tal
ity
.[98]Howev er,noc l
earbenefi
twass hownwiththeus eofhigh-dose
c
orti
cos teroi
dsf orseveresepsisors ept
icshock.
[98]

IntheCORTI CUS( Cor ti

costeroidTherapyofSept i
cShoc k)study,al
ar ger andomi z
edt ri
alof
hydr oc
orti
sonev ersusplaceboi npatientswithsepticshock,nodiff
er encei nmor t
ali
tywas
notedbet weent hegr oups,event hought hepati
entswhor eceivedsteroidshadamor erapid
resoluti
onofs hock,asmeas uredbyas hort
erdurat
ionofv asopress
ort herapy[99]anda
fasterimprovementi nSequent i
alOrganFai l
ureAssess
ment( SOFA)s c ores.[
100]Howev er,t
he
i
ncidenc eofsuperinfecti
onandr ecurrentsepsi
swashi gherinthosewhor ecei
veds t
eroids.

Additi
onally
,ther esul
toft hecort
isolstimul
ati
ont esthadnobear i
ngonout c
omei nthe
CORTICUSt ri
al,[
99]whi c hrai
sesques t
ionsaboutthev al
ueofthistesti
ndet ermi
ningwhowi ll
benefi
tf r
om s teroidtreatment.Howev er,t
heCORTI CUSs tudyenroll
edallpati
entswithsepti
c
shock,regardlessofv asopressorresponse.Consequently
,pati
entsinthi
ss tudyhadal ower
mortali
tythant hos eint heAnnanes tudy.

Gui
del
inesr
ecommendat
ionsands
ummar
yofkeypoi
ntsr
egar
dings
ter
oids

The2012Sur vi
vi
ngSeps i
sCampaigngui
deli
nesemphasi
zethatsteroi
dsshouldnotbe
admini
steredtopati
entswit
hs ept
ics
hockunlesshemodynamicstabi
li
tycannotbeac hi
eved
withfl
uidresus
cit
ati
onandv as
opress
oragents.
[11]I
nadditi
on,t
hes egui
deli
nes[11,60]and
thoseoftheACCCM[ 65]rec
ommendt hefoll
owing:

Donotus
etheACTHs t
imul
ati
ontestt
oidenti
fyt
hes ubs
etofadul
tpat
ient
swi
ths
ept
ics
hoc
k
(
orARDS)whoshoul
drecei
vehydr
ocort
isone[
11,60,65]

Donotadminis
t erdexamet
has
onewhenhy drocort
isoneisav
ail
abl
e;fl
udrocor
tis
oneis
opt
ionali
fhydrocorti
sonei
sused,butwhenhydrocort
isonei
snotavai
labl
eandt he
subs
tit
utedster
oiddoesnothav
es i
gni
fi
cantmi
ner
alocor
tic
oidac
tiv
ity
,cons
iderdai
ly
admini
str
ati
onoforalfl
udroc
ort
isone(
50goncedail
y)[
11,60]

TheACCCMal
sohast
hef
oll
owi
ngt
reat
mentr
ecommendat
ions
[65]:

Forpati
entswi
thsept
icshock,adminis
t erhydrocort
isone200mg/ dayI
Vi n4di v
ideddos
esor
asa100-mgbolusfol
lowedbyc onti
nuousi nfusi
onat10mg/ hr(240mg/ d);inpati
ent
swith
ear
lysever
eARDS,theopti
mali ni
ti
altreatmentr egi
meni sconti
nuousinfusionof
methyl
predni
sol
one1mg/ kg/day

Althoughtheopti
malt reatmentperi
odforc ort
icos
teroi
dsinpati
entswithsepti
cs hockand
earlyARDSremainstobedet ermined,aregimenof7day sorlongershoul
dbeus edinpatient
s
withsepti
cshockpr ovidedthatsi
gnsofs epsi
sors hoc
kdonotr ecurbeforetaperi
ng,anda
regimenof14day sorlongershouldbeus edinpati
entswit
hear l
yARDSbef oretaperi
ng

Donotus
edex
amet
has
onet
her
apyf
ors
ept
ics
hoc
korARDS

Thef
oll
owi
ngkeypoi
ntss
ummar
izeus
eofc
ort
icos
ter
oidsi
nsept
ics
hoc
k:

Ol
der
,tr
aditi
onalt
rial
sofcort
icos
ter
oidsi
nseps
iswer
euns
ucc
ess
ful
,pr
obabl
ybec
aus
eof
hi
ghdosagesandpoorpat
ientsel
ect
ion

Morer
ecenttri
alswi
thlow-dose(phys
iol
ogic)dosagesi
nselectpati
entpopul
ati
ons(
thos
e
wit
hvasopres
sordependenceand,possi
bly
,relat
iveadr
enali
nsuffi
ci
ency)mayhaver
esul
ted
i
nimprovedoutcome

Corti
coster
oids(
hydrocor
tis
one)shouldbeconsi
der
edonl
yforpat
ientswithvasopr
essor-
dependentsepti
cshock[65];weansteroi
dther
apywhenvas
opres
s orther
apyisnolonger
needed[11,60]

Consi
dermoder at
e- dosecortic
os ter
oidsinthemanagementofpat ientswithear
lysev
ere
ARDS( ar
teri
aloxygent ensi
on[ PaO2] /fr
act
ionofinspi
redoxygen[FI O2]<200),aswellas
bef
oreday14i npat i
entswi t
hunr esolvi
ngARDS[ 65];i
nvest
igatorss t
il
lneedtodeter
mi ne
whatrolecort
icos
t eroi
dt r
eatmentmayhav einl
esssevereARDS( PaO2/ FIO2>200)[65]

Acort
isols
timulati
ontes
tmaybeperfor
medtoident
ifypati
ent
swit
hrel
ati
veadr
enal
i
nsuf
fic
iency,defi
nedasfai
lur
etoi
ncr
easel
evel
sbymor ethan9g/
dL

Donotadmi
nis
terc
ort
icos
ter
oidst
otr
eats
eps
iswhens
hoc
kisnotpr
esent[
11,60]

Mai
ntenancester
oidt
herapyorstr
ess
-dosester
oidsmaybec ont
inuedasneededont
hebas
is
oft
hepatient
sendoc
rineorcor
tic
ost
eroi
d-adminis
trat
ionhi
stor
y[ 11,60]
Gl
ycemi
cCont
rol

ABel gianst
udyofc ri
tical
lyil
ls ur
gicalICU( SICU)pat i
entsfounda10% mor talit
ybenef i
tin
thos ewitht
ighterglyc
emi cc ontr
olwhent hegl ucos
el ev
elswer emaintai
nedbet ween80and
110mg/ dLthroughintensiv
ei nsuli
nt herapy.[101]Howev er,subsequentlarge,randomized
studiesdidnotrepli
catether esult
sf r
om t heBel gianstudy[102,103,104]Inf act,i
ntensi
ve
i
ns uli
nt r
eat
menthasbeens hownt ol eadtoi ncreasedepisodesofhy poglyc
emi aand
i
nc reasedmortali
tyi
nI CUpat i
ents.
[104,105,106,107]

Onthebasi
softhec
urrentevi
denc
e,t
heSurv
ivi
ngSeps
isCampai
gngui
del
inesr
ecommend
mai
ntai
ningagl
ucos
elevelbel
ow180mg/dL.
[11]

DVTPr
ophy
lax
isandManagementofDI
C

Deepv
eint
hrombos
is

TheSev er
eSepsi
sCampaignguidel
ineshavet
hefoll
owingrecommendat
ionsorsuggesti
ons
regar
dingprophy
lax
isofdeepveinthrombosi
s(DVT)inpat
ientswi
thsev
ereseps
is[11,60]:

Intheabsenceofcontr
aindicat
ions(
eg,ac
tiv
ebl eedingorthr
omboc ytopenia)
,administer
eit
herlow-doseunfr
acti
onatedhepari
n(UFH;2or3t imesdai
ly)orl
ow- molecular
-weight
hepari
n(LMWH) ;LMWHmaybepr ef
err
edinv er
yhi ghri
skpati
ents(eg,pati
entswi t
hs ever
e
sepsi
sandpr ev
iousDVT,trauma,orort
hopedicsurgery)

I
fthepat
ient
sc
reat
ini
nec
lear
anc
eisl
esst
han30mL/
min,dal
tepar
inmaybeus
ed

I
nthepr es
enceofc ontr
aindicat
ionsforhepari
nuseandintheabsenceofot
her
c
ontraindi
cat
ions,usemec hanic
al DVTprevent
iondevi
ces(
eg,graduat
edcompres
sion
s
tockings[GCS]orinter
mi tt
entc ompressi
ondevic
es[I
CDs])

I
nveryhighris
kpatients,considerc
ombiningphar
macol
ogi
candmechani
calpr
ophy
lac
tic
t
herapyunles
sc ont
raindic
ationsexis
torsuchther
apywoul
dbeimpr
acti
cal

(
SeeDeepVenousThrombosi
s,Thr
omboembol
is
m,andGener
alPr
inc
ipl
esofAnt
icoagul
ati
on
i
nDeepVenousThrombosi
s.
)

Di
ssemi
nat
edi
ntr
avas
cul
arc
oagul
ati
on
DIC,ac onditi
oninwhichbleedingandt hrombosi
soccur,c ancontri
butet omul t
iorgansystem
fai
lureandc arr
iesahi
ghmor t
alit
y.Althoughcont
rovers
yex i
stsregardi
ngDI Ct r
eat ment,t
he
overallmanagementstrat
egyi stotreattheunder
lyi
ngc aus eandprov i
des upporti
vec ar
e(see
Correc t
ionofanemiaandcoagul opathyunderGener
alTr eatmentGuidelines).

In2009,theBr i
ti
shCommi t
teeforStandar
dsi nHaematology(BCSH)publishedt heir
guidel
inesrecommendat ions,inwhichtheystatethatt
reati
ngt heunderl
yinget i
ologyis t
he
corner
s t
oneofDI Ctherapy .
[108]TheBSCHgui deli
nesregardi
ngadjuncti
v etreatment( eg,
plasmaandpl at
elett
rans fusi
on,anti
coagulat
ion,useofantic
oagulantfac
torc onc entr
ates,
andant i
fi
brinol
yti
ctherapy )aredi
scussedbelow.

Pl
asmaandpl
atel
ett
rans
fus
ion

I
ngener al,theBSCHr ecommendsr eservi
ngtransfusionofplatel
et sorpl
as ma( components)
forpat i
ent swithDICwhoar ebl eedi
ng( r
atherthanadmi nis
teringt hi
stherapyont hebas
isof
l
abor atoryf i
ndings)
.Thus,platelett
ransfusi
ons houldbecons i
der edinpatientswi t
hDICand
bleeding( orahi ghr
iskofbleeding)whohav eapl atel
etcountbel ow50109/ L
(50,000/L) .
[108]TheSurvivingSeps i
sCampaigns uggestscons i
der i
ngplatelettransf
usi
onin
suchpat ientswhenpl at
eletcount sarebelow20109/ L(20,000/L).[
11]

Ot
herBSCHpl
asma/
plat
elett
rans
fus
iongui
del
inesi
ncl
udet
hef
oll
owi
ng[
108]:

Donotadmi
nis
terpr
ophy
lac
ticpl
atel
ett
rans
fus
ionsi
nnonbl
eedi
ngpat
ient
sunl
esst
heyar
eat
hi
ghri
skofbl
eedi
ng

Consideradmini
steri
ngFFPinpatient
swithDICandacti
vebleedi
ngwhohav epr olonged
prot
hr ombinti
me( PT)andac
t i
vat
edpart
ialt
hromboplast
inti
me( aPTT),aswellast hosewho
mayunder goaninvasi
veprocedur
e;donotadminis
terFFPsolel
yont hebasisofl aborat
ory
fi
ndings

Consideradminist
eringfactorconcent
rates(
eg,prot
hrombi
ncompl
exconc
entr
ate)i
fFFP
cannotbet r
ansfused;notet hatt
heseagentscont
ainonl
ysel
ect
edf
act
orsandwil
lnot
completel
yc or
recttheDI C

Cons
ideradmi
nis
ter
ingf
ibr
inogenc
onc
ent
rat
eorc
ryopr
eci
pit
atei
ncas
esofper
sis
tents
ever
e
hy
pof
ibr
inogenemi
a(<1g/
L)des
pit
eFFPt
her
apy

Ant
icoagul
ati
on

Ther
apeut
icdos
esofhepar
ins
houl
dbec
ons
ider
edi
nthef
oll
owi
ngc
li
nic
als
ituat
ionsof
DIC[
108]:

Whent
hrombos
ispr
edomi
nat
es(
eg,ar
ter
ialorv
enoust
hromboembol
is
m)

Inthepr
esenc
eofs
ever
epur
pur
aful
minanswi
thas
soc
iat
edi
nadequat
eper
fus
iont
othe
ext
remit
ies

I
nthepr
esenc
eofv
asc
ulars
kini
nfar
cti
on

Cont i
nuousi nf
usionofUFHs houldbeconsider
edinpatientswit
hDI Cwhoareathighri
skof
bleeding;forexample,wei
ght-adjust
eddoses(eg,10U/kg/hr)maybeusedwithoutthe
i
nt enti
ont oprolongtheaPTTr ati
oto1.
5-2.5ti
mest hecontrol
.
[108]Cl
osemonitori
ngof
thesepat i
entsisrequi
redforsignsofbl
eedingandfortheiraPTTmeasurement
s .

DVTprophy
lax
iswit
hprophyl
act
icdosesofhepari
norLMWHi
srec
ommendedf
orc
rit
ical
lyi
ll
pat
ient
swit
hDI Cwhoarenotac
tiv
elybleedi
ng.
[108]

Ant
ifi
bri
nol
yti
cther
apy

I
ngener al
,theBSCHdoesnotrec
ommendadmi nist
eringant i
fi
brinol
yti
cagentstopatients
wit
hDI C.[
108]Inpati
ent
swhohav eDICt hati
sc harac
t er
izedbyapr i
mar yhyper
fibr
inolyt
ic
st
ateandwhopr es
entwit
hsev
erebleeding,admi ni
str
at i
onofl y
sineanalogues(
eg,
tr
anexamicacid1gq8hr)maybeconsidered.

ManagementofAc
uteRes
pir
ator
yDi
str
essSy
ndr
ome

ARDSandALI( nowoftenrefer
redtoasmi l
dARDS,i naccordancewi t
htheBer l
in
Defi
niti
on[
10])aremajorc ompl
icati
onsofs epsi
sandsepti
cs hock.Theinci
denceofARDSi n
septi
cshockr
angesfrom 20% to40% andi shigherwhenapul monarysourceofinf
ecti
on
exi
sts.(
SeeAcuteRes
piratoryDis
tressSyndromeandPediatri
cAc uteRes pi
rat
oryDist
ress
Syndrome.
)
ARDSc anbeas sociat
edwi thcl
ini
caldi sorderscausi
ngdirectlunginjury,suchasgas t
ricaci
d
aspir
ati
on,thoraci
ct r
auma,pneumoni a,andneardr owning;orindi
rec tl
ungi njury
,incl
uding
severesepsi
s,acut
epanc reati
ti
s,drugov erdose,r
eperfus
ioninjur
y,ands ever
enont horaci
c
trauma.Sepsi
s-associ
atedARDSc arr
iesanaby smalprognosisandc arri
est hehighest
mor t
ali
ty.

ManagementofARDSi spr i
maril
ysuppor t
ive;pharmacologicandot herinnov at
ivet herapi
es
havenotpr ovedes peci
all
ybenefici
al.Generalsupporti
vec arei
ncludesadequat et reatmentof
underl
yi
ngs eps i
swithappropr
iateantibi
oticsands ur
gicalmanagementi findic
at ed.
Appropriat
ef luidmanagementt olowerintravascul
arvolumewi thoutaffect i
ngc ardiacoutput
andorganper fusi
onmaybebenef i
ci
al.Thef l
uidmanipulationoftenrequiresinvas i
ve
hemody nami cmoni t
ori
ng.

Thegoal
sofmec
hani
calv
ent
il
ati
oni
ncl
udet
hef
oll
owi
ng:

I
mpr
ovi
nggasex
change

Reduc
ingwor
kofbr
eat
hing

Av
oidi
ngox
ygent
oxi
ci
ty

Mi
nimi
zi
nghi
ghai
rwaypr
ess
ures

Av
oidi
ngf
urt
herl
ungdamage

Al
lowi
ngt
hei
njur
edl
ungt
oheal

Alung- pr
ot ect
iveandpressure-l
imitedv enti
lat
orystr
ategyhasbeenshownt oi
mprove
survi
valratesandlowerratesofbar otrauma.Cur r
entrecommendati
onsaretouseat i
dal
volumeof5- 8mL/kg,toempl oyalongeri nspir
atoryt
ime,andnottoexceedatrans
pulmonary
pressureof30c m H2O.Per mi s
sivehyper capni
amayens uemayoc c
urwiththeuseofles
ser
ti
dalv ol
umes ,butiti
stoler
ated.

Theus eofPEEPmayr educeorpreventv ent i

lator-induc edlunginjur
y.Suff
icientPEEPto
recr
uitatel
ect
aticalveol
arunit
sandt oincreas elungv olumessot hatrespi
rationhappenson
themos tcompliantpartofthepres
s urev olumec ur v
ei srecommended.I nc l
inic
al pr
act
ice,
thi
sc anbeachievedbymeas uri
ngpl ateaupr ess uresandc al
culat
inglungcompl ianceat
dif
ferentlev
elsofPEEP.Theuseofproneposi
ti
oni
ngandNOmayprovet
obebenef
ici
ali
nthe
shortterm;thesei
nter
venti
onshavenotbeenshowntoi
mprov
esur
viv
alrat
es.

High-dosec or
tic
os ter
oids,thoughnotus ef
ulinearlymanagement ,cani
mpr ovesurvi
valin
pati
ent swhoseARDSi snotr esol
vi
ng.Inas t
udybyMedur ietal,prol
ongedadmi nis
trationof
methy l
prednis
olonei npat i
entswit
hnonr es
olvingARDSwasas s oci
atedwit
hi mprovement
andr educedmor t
ality.
[109]Mor t
ali
tywas0/ 16(0%)f orthetr
eat mentgroupand5/ 8(62%)
fortheplacebogr oupint heICU.Therateofinfect
ions ,i
ncl
udingpneumoni a,wass i
milarin
the2gr oups.Moreev idenceisneededregardingsteroiduseandARDS.

Sur
gic
alTr
eat
ment

Pati
entswi t
hfocalinfec t
ionss houldbesentf ordefi
niti
ves ur
gicaltreatmentaf teriniti
al
res
us ci
tati
onandant ibiotictherapy.[
2]Lit
tleisgainedbys pendinghour sstabil
izi
ngt he
pati
entwhi l
eaninfectedf oc uspersist
s.Howev er
,ev enthoughur gentmanagementi s
warrantedforhemody nami cal
lystabl
epatientswithoutevidenceofac uteorganf ai
lure,itmay
bepos si
bletodelayinv asi
v eproceduresupto24hour spr ovi
dedt hatv erycloseclini
cal
moni t
oringisi
nstit
utedandappr opri
ateantimicr
obialtherapyadmi nistered.
[2]

Anys oft-
tissueabs cesss houldbedr ai
nedpr ompt l
y.Cer t
ainc onditi
onswi l
lnotres
pondt o
standardtreat mentfors epticshockunt i
lthes ourceofinfectionissurgical
lyremoved.Some
ofthesec ommonf ociofinfecti
oninc l
udeintra-abdomi nalsepsis(perfor
ationorabscess),
empy ema,medi as
tiniti
s,cholangit
is,pancreaticabscess,pyelonephriti
sorrenalabscessfrom
ureteri
cobs t
r ucti
on,infec t
iveendoc ar
dit
is,septicarthri
ti
s,infectedprostheti
cdevices,deep
cutaneousorper i
rectalabscess,andnec roti
zingfasciit
is.

Whenev erpossi
ble,per
c utaneousdrai nageofabs cessesandot herwel l
-l
oc al
izedfl
ui d
coll
ect
ionsispreferr
edt os urgi
caldrainage.[
2]Forex ampl e,asuperfici
alabs cesscanbe
drai
nedint heED.Howev er,anydeepabs c
essors uspectednec roti
zingfasc i
it
isshoul dbe
drai
nedint hesur
gicalsuite.Otherex amplesofemer genc yc ondit
ionsthatc allf
orr apid
managementar ediffus
eper i
toni
tis,
c holangit
is,andintestinali
nfarcti
on.[11,60]

I
nc as
esofsepsi
sofuncl
earet
iol
ogy
,athoroughs
earchforabs
ces
sess
houl
dbeper
for
med,
wit
hpart
icul
aratt
enti
onpaidt
otherec
talandper
ianalar
ea.
Pr
event
ion

Pat
ientswit
himpai
redhostdef
ens emechani
smsar
eatgr
eat
lyi
ncr
eas
edr
iskf
ors
eps
is.The
maincausesofi
mpair
edhostdefensear
easfoll
ows:

Chemot
her
apeut
icdr
ugs

Mal
i
gnanc
y

Sev
eret
rauma

Bur
ns

Di
abet
esmel
li
tus

Renalorhepat
icf
ail
ure

Adv
anc
edage

Venti
lat
orysuppor
tandinvas
ivecathet
ersf
urt
herinc
reas
ether
iskofi
nfect
ion.Avoi
dingt
he
useofcathet
ersorremovi
ngthem assoonasposs
ibl
emayprev
entsever
esepsis.

Prophy l
acticanti
biotic
si ntheperi
operati
vephase,particul
arlyafterGIsurgery,maybe
benef i
cial
.Theus eoft opic
alanti
bioti
csaroundinvasiv
ec athetersandaspar tofdres
singsf
or
patientswithburnsi shelpful
.Otherpreventi
vemeas uresincludemaintenanceofadequate
nutriti
on,admi ni
strati
onofpneumoc occ
al v
acci
nei npatientswhohav eunder gone
splenectomy ,andearlyenteralf
eeding.

Pr
eventionofsepsi
swit
htopicalorsyst
emi canti
biot
icsi
ss uggest
edforhigh-
ris
kpatient
s.
Useofnonabsorbabl
eanti
biot
icsinthest omachtopreventtrans
locat
ionofbacter
iaand
oc
currenceofbacter
emiai
sac ontrover
siali
ssue.

Numer oustri
alshavebeenper f
ormed,us ingeithert opicalantibiot
icsal
oneorac ombinati
on
oft opi
c alandsystemicanti
bioti
cs.As yst
emi creviewbyNat hensfoundnobenef i
tinmedical
patientsbutdoc ument edareducedmor tali
tyins urgicaltraumapat ient
s.[
110]Thebenefici
al
effectwasac hievedwithacombi nati
onofs ys t
emi candt opicalanti
biot
ics,pr
edominantl
yby
reduc i
ngl owerrespi
ratoryt
ractinfec
tionsint r
eat edpat i
ent s.
Progressi
onfrom infecti
onwi t
hs ys
temicinfl
ammatoryresponsesyndrome( i
e,sepsi
s)to
severesepsi
swi t
hor gandy sf
uncti
ont osepti
cshockwithrefr
actoryhypotensi
onc anoftenbe
revers
edwi t
hear l
yidentif
icati
on,aggres
sivecry
stal
loi
dflui
dresuscit
ati
on,broad-spect
rum
antibi
oti
cadmi ni
strati
on,andr emovaloftheinf
ecti
oussourceifpossi
ble.

Bas
icmeas
urest
opr
eventnos
ocomi
ali
nfec
tionsi
ncl
udet
hef
oll
owi
ng[
54]:

Shor
teni
ngt
hehos
pit
als
tay

Remov
ingi
ndwel
li
ngc
athet
ersasear
lyaspos
sibl
e

Av
oidi
ngunnec
ess
aryi
nvas
ivepr
ocedur
es

Us
ingas
ept
ict
echni
ques

Medi
cat
ion