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Pierrakos and Vincent Critical Care 2010, 14:R15 http://ccforum.


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!epsis %iomarkers: a re&ie'
Charalampos Pierrakos, (ean)*ouis Vincent
"%stract ,ntroduction: -iomarkers can %e useful for or rulin/ out sepsis, patients 'ho ma. %enefit from specific therapies or assessin/ the response to therap.. 0ethods: 1e used an electronic search of the Pu%0ed data%ase usin/ the ke. 'ords 2sepsis3 and 2%iomarker3 to identif. clinical and e4perimental studies 'hich e&aluated a %iomarker in sepsis. Results: 5he search retrie&ed 6670 references co&erin/ 178 different %iomarkers. Conclusions: 0an. %iomarkers ha&e %een e&aluated for use in sepsis. 0ost of the %iomarkers had %een tested clinicall., primaril. as pro/nostic markers in sepsis9 relati&el. fe' ha&e %een used for dia/nosis. :one has sufficient specificit. or sensiti&it. to %e routinel. emplo.ed in clinical practice. PC5 and CRP ha&e %een most 'idel. used, %ut e&en these ha&e limited a%ilit. to distin/uish sepsis from other inflammator. conditions or to predict outcome. ,ntroduction
!epsis is a leadin/ cause of death in criticall. ill patients despite the use of modern anti%iotics and resuscitation therapies ;1<. 5he septic response is an e4tremel. com) ple4 chain of e&ents in&ol&in/ inflammator. and anti) inflammator. processes, humoral and cellular reactions and circulator. a%normalities ;2,6<. 5he dia/nosis of sepsis and e&aluation of its se&erit. is complicated %. the hi/hl. &aria%le and non)specific nature of the si/ns and s.mptoms of sepsis ;4<. #o'e&er, the earl. dia/no) sis and stratification of the se&erit. of sepsis is &er. important, increasin/ the possi%ilit. of startin/ timel. and specific treatment ;5,=<. -iomarkers can ha&e an important place in this pro) cess %ecause the. can indicate the presence or a%sence or se&erit. of sepsis ;7,8<, and can differentiate %acterial from &iral and fun/al infection, and s.stemic sepsis from local infection. $ther potential uses of %iomarkers include roles in pro/nostication, /uidin/ anti%iotic ther) ap., e&aluatin/ the response to therap. and reco&er. from sepsis, differentiatin/ >ram)positi&e from >ram) ne/ati&e microor/anisms as the cause of sepsis, predict) in/ sepsis complications and the de&elopment of or/an d.sfunction ?heart, kidne.s, li&er or multiple or/an d.s) function@. #o'e&er, the e4act role of %iomarkers in the mana/ement of septic patients remains undefined ;A<.
+ Correspondence: Bl& Department of ,ntensi&e Care, rasme #ospital, Eni&ersitF *i%re de -ru4elles, route de *ennik 808, 1070 -russels, -el/ium

C)reacti&e protein ?CRP@ has %een used for man. .ears ;10,11< %ut its specificit. has %een challen/ed ;12<. Pro) calcitonin ?PC5@ has %een proposed as a more specific ;16< and %etter pro/nostic ;14< marker than CRP, althou/h its &alue has also %een challen/ed ;15<. ,t remains difficult to differentiate sepsis from other non) infectious causes of s.stemic inflammator. response s.ndrome ;1=<, and there is a continuous search for %et) ter %iomarkers of sepsis. 1ith this %ack/round in mind, 'e re&ie'ed the litera) ture on sepsis %iomarkers that ha&e %een used in clinical or e4perimental studies to help %etter e&aluate their utilit..

0aterials and methods
5he entire 0edline data%ase 'as searched in Ge%ruar. 200A usin/ the ke. 'ords HsepsisI and H%iomarkerI. "ll studies, %oth clinical and e4perimental, 'hich e&aluated a %iomarker 'ere included. Gor each identified %iomar) ker, the 0edline data%ase 'as searched a/ain usin/ the %iomarker name and the ke. 'ord H%iomarkerI.

" total of 6670 studies that assessed a %iomarker in sep) sis 'ere retrie&ed9 178 different %iomarkers 'ere e&alu) ated in the 6670 studies. 5he retrie&ed %iomarkers and the maBor findin/s from ke. studies usin/ these %iomar) kers are listed in 5a%les 1, 2, 6, 4, 5, =, 7, 8 and A. $f the 178 %iomarkers, 18 had %een e&aluated in

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%ut also other patho) Pa/e 2 of 18 5a%le 1 C... comple4 pathoph.17< and in patients 'ith "lNheimerIs disease. a stud. D.) four %iomarkers 'ere identified that ha&e %een assessed for use specificall. "dditionall. e4perimental studies onl. %e useful &aries.==.52< . Bust 8 %iomarkers 'ere identi) fied . of patients 'ith m. in e4perimental models.42.s .76< 0onoc.pes.42.=8.7=. . 'ith less than 20 patients9 -.71.*)1 receptor anta/onist . mediators of inflammation .9 0$G: multiple or/an failure9 !$G": seMuential or/an failure assessment. as the sepsis response &aries 'ith time. and specificit. and this is difficult to assess relia%l.stem acti&ation.. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. 'ith 20 to 50 patients9 C.stemic nature of sep) sis and the lar/e num%ers of cell t. man.5=.C #i/her in septic shock than sepsis. .*)16 .. complement.5A< . and apoptosis are all in&ol&ed in the sepsis process.57< .75< R":5 ! .s Predicti&e of lethal outcome from postoperati&e sepsis #i/her in septic shock than sepsis Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. of less than A0L9 +++sensiti&it. /roup)%o4 1 protein ?#0>-)1@ .51.78. Clinical stud.58< .*)10 . 58 in %oth e4perimental and clinical studies. and not e4peri) mentall.te chemotactic protein ?0CP@)1 and 2 .s .1A<. more than in other disease pro) cesses9 for e4ample.s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. and specificit.stem ha&e %een proposed ?5a%les 1 to A@. Discussion " multitude of %iomarkers has %een proposed in the field of sepsis.P@)1 and) 2 . 'hich in&ol&es man.s Correlation 'ith !$G" score . pro%lems 'ith spe) cies differences.=A< .4A.siolo/.ncreased in septic compared 'ith non)septic indi&iduals .72< 0acropha/e mi/ration inhi%itor.siolo/ical mechanisms.ncreased le&els associated 'ith de&elopment of sepsis Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. "dditionall.*)1% .*)8 .56)55< . the e4act time period durin/ 'hich an.18<. contact s. 5hirt. inflammation. compared 'ith disease processes that in&ol&e indi&idual or/ans or are more localiNed. more than A0L9 ". and separate mar) kers for each ?part of each@ s. Clinical stud. of sepsis.70< 0acropha/e inflammator. protein ?0. medical patients onl. 5his is likel.s Prediction of 0$G. of less than A0L9 ++sensiti&it. the s.=6)=5< .50< #i/h mo%ilit.7A< #i/her in septic shock than in sepsis :o difference %et'een sur&i&ors and non)sur&i&ors at 28 da. Coa/ulation.=1.s in patients 'ith septic shock K K K+ K+++ K++ K K K K K++ K+ K K K K K K K K K K +sensiti&it. to %e related to the &er. tissues and or/ans in&ol&ed e4pand the num%er of potential %iomar) ker candidates.*)= .ocardial infarction re&ealed 14 %iomarkers suita%le for dia/nosis and determination of pro/nosis . controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.*)12 .74< $steopontin . 5his lar/e difference in the num%ers of %io) markers for sepsis is likel.ncreased in sepsis compared 'ith health. and pro%lems in determinin/ end)points in animal studies. 'ith more than 50 patients9 ?s@. of more than A0L %ut specificit. distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.Pierrakos and Vincent Critical Care 2010.tokine/chemokine %iomarkers identified in the literature search ?'ith some selected references@ !epsis marker &aluated in e4perimental studies K K K K &aluated in clinical studies C ?m@ C " " C ?s@ K C -?s@ " " C &aluated as a pro/nostic factor K K K Comment >R$)alpha .67.77< 5:G .48.=0< ..9 ?m@.ncreased in parallel 'ith disease se&erit.G@ .*)4 . 0ore) o&er. factor ?0. and 101 in clinical studies onl.=7< . controls . specific %iomarker ma.t is interestin/ to note that most of the %iomarkers 'e identified ha&e %een tested clinicall.ncreased in sepsis compared 'ith health. 14:R15 http://ccforum. &alues /reater than A0L..*)2 .C: disseminated intra&ascular coa/ulopath. reflects all aspects of human sepsis. as there is no H/old standardI for the dia/nosis of . in the dia/nosis of sepsis ?5a%le 10@9 of these Bust fi&e reported sensiti&it.*)18 . to %e in part related to difficul) ties creatin/ an e4perimental model that accuratel.ncreased in sepsis compared 'ith health. D. sur/ical patients onl.=2< . and specificit. Clinical stud.

ill patients de&elop some de/ree of inflammator.ears. and specificit. assessed as potential %iomarkers are the c. mak) in/ interpretation difficult..A0< CD=4 .24< and cardiac sur/er.8=< CD25 ?cellular and solu%le@ .26<. of less than A0L9 ".28<.ndrome. i.27<. rapidl.21. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.A4< K K Decreased in septic shock compared 'ith health.27. and sensiti&it. 'hether or not the. lo' ?t. controls Correlation 'ith "P"C# .siolo/. and specificit.5a%le 2 Cell marker %iomarkers identified in the literature search ?'ith some selected references@ !epsis 0arker &aluated in e4perimental studies K K &aluated in clinical studies " -?s@ " C &aluated as a pro/nostic factor Comment CD10 .n a clinical stud. 5he dia/nosis of sepsis is a challen/e. . &aria%les .s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.. . Clinical stud. %e helpful to e&aluate the response to therap. rou) tinel.ncreased in sepsis compared 'ith health. used in clinical practice %ecause of its /reater a&aila%ilit. cases. PC5 has %een used particularl. the com%ination of clinical si/ns and a&aila%le la%orator. 10 %iomarkers that ha&e %een assessed for their a%ilit.25<. none of these %iomarkers has %een tested for %oth sensi) ti&it..A2< CD80 . of PC5 for the dia/nosis of sepsis is relati&el. %elo' A0L@.82.siolo/. the effecti&eness of a %iomarker needs to %e com) pared 'ith current methods used to dia/nose and moni) tor sepsis in e&er.8<. #o'e&er. effort and costs to measure. it is freMuentl. controls Predicted de&elopment of septic shock Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. of its time course ma. in recent . maBor sur/er. and chronic health e&aluation9 !$G": seMuential or/an failure assessment. to distin/uish septic patients from non)septic patients 'ith s. sepsis.84< CD14 ?cellular and solu%le@ .11<. such as trauma . sur/ical patients onl. o%tained. relati&el. and the stud. and !$G" scores . used in clinical studies. after sep) sis onset. and there is therefore no %iomarker clearl.8A< CD48 . &en micro%iolo/ical assessment is unrelia%le %ecause man. and &alidit. response.A1< CD=A . !ome are alread. identified as %ein/ a%le to differentiate sepsis . le&els of 5:G and . ha&e sepsis.s in patients 'ith septic shock K " " C C K K K K K K+ +sensiti&it.80.*)10 'ere increased 'ithin the first 24 hours after admission of the patient . used for other purposes and easil. Clinical stud.ield microor/anisms in these patients. e4tensi&el. controls Correlation 'ith !$G" score Decreased in septic shock compared 'ith health. the relia%ilit.stemic immune response s.tokine concentra) tions are rather erratic and their time course is not clearl. "P"C# : acute ph. $f the man.81< CD11% .da. reMuire considera%le time. and most are produced fairl.A6< m#*")DR ?solu%le@ .88< CD40 ?cellular and solu%le@ . Raised PC5 le&els ha&e also %een reported in other conditions associated 'ith inflamma) tor. response. culture samples do not ..tokines.. "nother /roup of compounds that has %een 'idel. le&ated concentra) tions of serum CRP are correlated 'ith an increased risk of or/an failure and death .s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. of sepsis. more potential %iomarkers for sepsis than are currentl. Clinical and standard la%orator. 'ith more than 50 patients9 ?s@.85< CD18 . !ome of these markers ma. . re&ealed that there are man. %iomarkers ha&e also not %een sho'n to %e a /reat asset in the dia/nosis of sepsis. .87< CD28 ?solu%le@ .n man. Clinical stud. . #o'e&er. assessed. such as coa/ulation tests or cholesterol concentrations. acute phase proteins ha&e perhaps %een most 'idel.22<. clinical practice. .. #o'e&er. 'ith less than 20 patients9 -. 'ith 20 to 50 patients9 C.88< CD1=6 ?solu%le@ . helpful %ecause most criticall. re/ardless of the cut)off &alue . $ur search retrie&ed onl.ncreased in sepsis compared 'ith health. fe' %iomarkers ha&e %een e&aluated as dia/nostic markers ?5a%le 10@.86< CD11c . 5he specifi) cit.2=<. in septic patients . %lood c.s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. $ur stud.s .20<9 e4perimental models cannot %e used for this purpose. tests are not &er. proposed markers for sepsis. "lthou/h CRP is often reported as inferior compared 'ith PC5 in terms of sepsis dia/nosis. of the proposed %iomarker ha&e not %een tested properl.picall. in concert 'ith the course of sepsis .ndeed. 5hese are important mediators in the pathoph.e. %.

. Clinical stud.121< 5hrom%omodulin .11=< Gi%rin . P5 .108< 5oll)like receptor ?5*R@ 2 and 4 . 'ith 20 to 50 patients9 C. Clinical stud.ncreased in sepsis compared 'ith health.102< >P160 .65< D)dimers. 'ith 20 to 50 patients9 C. and specificit. . 'ith more than 50 patients9 ?s@.112< 5:G)receptor ?solu%le@ .11A< Protein C and ! .C: disseminated intra&ascular coa/ulopath. phospholipase "2 ?P*"2).cation end)products. C C " K K C C K K K K+ K +sensiti&it. G1.s.@ ?solu%le@ . controls .100< G*5)1 ?solu%le@ . 5a%le 4 Coa/ulation %iomarkers identified in the literature search ?'ith some selected references@ !epsis marker &aluated in e4perimental studies K &aluated in clinical studies C &aluated as a pro/nostic factor K++ K Comment "ntithrom%in .siolo/. and specificit. Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s. Clinical stud. ill patients &aluated in clinical studies &aluated as a pro/nostic factor Comment CC chemokine receptor ?CCR@ 2 .9 ?m@.114< K K K+ K K K +sensiti&it.eloid cells9 R"> : receptor for ad&anced /l.s Predicted de&elopment of 0$G .AA< Gc)/amma R.C.A7< CR5h2 .C. of more than A0L %ut specificit.110< 5R 0)1 ?solu%le@ .118.106< .s Predicted de&elopment of 0$G.111. . 'ith less than 20 patients9 -.@)1 ..107< !52 ?solu%le. score Correlated 'ith "P"C# . correlated 'ith "P"C# . of less than A0L9 ".2.104< >roup . correlated 'ith "P"C# .ncreased in septic compared 'ith non)septic criticall. and chronic health e&aluation9 0$G: multiple or/an failure9 5R 0: tri//erin/ receptor e4pressed on m..ncreased in sepsis compared 'ith health. 'ith less than 20 patients9 -.s Correlated 'ith 0$G score in patients 'ith sepsis and D. score . hi/h ne/ati&e predicti&e &alue Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. 5"5.101.s Predicted de&elopment of 0$G Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da.117< Plasmino/en acti&ator inhi%itor ?P".122.115< "cti&ated partial throm%oplastin time ?aP55@ .126< Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. Clinical stud. Clinical stud..A5< CCR 6 . and response to therap.s . .10=< R"> ?solu%le@ . "PC# : acute ph.siolo/.. and chronic health e&aluation9 D.6=< PG)4 .ncreased in sepsis compared 'ith health.ncreased in patients 'ith >ram)ne/ati&e %acteremia Predicted response to therap. of less than A0L9 ".pe plasmino/en acti&ator receptor ?uP"R@ ?solu%le@ .116< Erokinase t.*)2 receptor ?solu%le@ . predicted de&elopment of 0$G Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.*)1 receptor@ .105. sur/ical patients onl. D.A=< C5*2 . 'ith more than 50 patients.s K K K K K K Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da. controls.s Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da.. of less than A0L9 ++sensiti&it.120.5a%le 6 Receptor %iomarkers identified in the literature search ?'ith some selected references@ !epsis marker &aluated in e4perimental studies K C K C -?m@ " K C " C "?s@ K K K C C?m@ K Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da. "P"C# : acute ph... Clinical stud. medical patients onl.10A< 5ransient receptor potential &anilloid ?5RPV@1 . score .s Predicted de&elopment of 0$G Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da. controls Predicted de&elopment of septic shock Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da.9 0$G: multiple or/an failure9 P5: prothrom%in time9 PG: platelet factor9 5"5: throm%in)antithrom%in comple4.A8< Gas receptor ?solu%le@ .

'ith more than 50 patients9 ?s@.148.165< )!electin ?cellular and solu%le@ .157< Predicted de&elopment of septic shock .me ?"C @ ?acti&it.156.152< C. correlated 'ith "P"C# .9 0$G: meultiple or/an failure9 !"P!: simplified acute ph. and specificit. predicted de&elopment of acute lun/ inBur.124.16=< *)!electin ?solu%le@ .12A.C"0@) 1 ?solu%le@ . controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. D.C compared 'ith no D.ncreased in sepsis compared 'ith health. Clinical stud.145.140< Vascular endothelial /ro'th factor ?V >G@ .5a%le 5 -iomarkers related to &ascular endothelial dama/e identified in the literature search ?'ith some selected references@ !epsis marker &aluated in e4perimental studies K &aluated in clinical studies K K -?s@ &aluated as a pro/nostic factor K K K K+ Comment "D"05!)16 .16A.9 ?m@.siolo/. correlated 'ith Predicted !"P! score Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da.l/l.151< C)t. predicted de&elopment of 0$G %et'een sur&i&ors and non)sur&i&ors Distin/uished at 28 da.C: disseminated intra&ascular coa/ulopath. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.150< Copeptin .142< &on 1ille%rand factor and anti/en .s.127.126. sur/ical patients onl.s Predicted de&elopment of septic shock Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da.s K -?m@ " K C K C C K K K K K K+ K K K+ .146. score .C Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da. score. Clinical stud.s Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da..160< ndothelial pro/enitor cells ?c PC@ .s. +sensiti&it.s Predicted de&elopment of 0$G C " -?m@ K K Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da. 'ith 20 to 50 patients9 C.128< ndothelial leukoc.s.ncreased in patients 'ith septic shock compared 'ith health.clin/ nucleotides .147< "n/iotensin con&ertin/ enN.15=.168< Vascular cell adhesion molecule ?VC"0@)1 .ncreased in sepsis compared 'ith health.s in patients 'ith se&ere sepsis de&elopment of 0$G. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.14A< 2)arachidono. controls .cerol .161< .154< lastin ..te adhesion molecule ? *"0@)1 ?cellular and solu%le@ .ntracellular adhesion molecule ?. of less than A0L9 ".141. controls " C?m@ " K "?m@ C?s@ K+ K K K . 'ith less than 20 patients9 -..164< Platelet)deri&ed /ro'th factor ?PD>G@) -. and serum@ ..ncreased in sepsis compared 'ith non)infected controls Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da. score . correlated 'ith "P"C# . Clinical stud.155< c>RP .ncreased in sepsis compared 'ith health.144< Decreased in septic patients 'ith D.125< "n/iopoietin ?1 and 2@ .68< *aminin .s Distin/uished %et'een sur&i&ors and non) sur&i&ors at 28 da.166.12=< ndocan .s Decreased in sepsis compared 'ith health.14=< "nandamide .pe natriuretic peptide ?C:P@ .162< :eopterin . 5a%le = -iomarkers related to &aosdilation identified in the literature search ?'ith some selected references@ !epsis marker &aluated in e4perimental studies &aluated in clinical studies K K " &aluated as a pro/nostic factor K+ Comment "drenomedullin and pro) adrenomedullin .s. medical patients onl.167< P)!electin .

ill patients .ncreased in tissue samples from patients 'ith peritonitis compared 'ith no peritonitis 5etrah.l/l. acidic protein ?>G"P@ . 'ith less than 20 patients9 -. 2 da. and specificit.sfun/si or/an .1A2< 5roponin .ocardial an/iotensin .ncreased in sepsis compared 'ith non)septic criticall.1=8.s ?predicti&e onl.1A6< 5ampak pada sur&i&ors dan non)sur&i&ors Pada 28 hari 5ampak pada sur&i&orsddan non)sur&i&ors pada 28 hari.. score K +sensiti&itas dan spesificitas kuran/ dari A0L9 ++sensiti&itas l e % i h d a r i A0L tapi spesifitas kuran/ dari A0L9 ".1=6< K K K -?m@ " C?s@ K K Correlated 'ith se&erit.1A0< !urfactant protein ?". score -erhu%un/an den/an !$G" scores Prediksi pem%an/unan dari 0$G 0enin/katpada s.182. 'ith 20 to 50 patients9 C.15A.te /ro'th factor ?#>G@ ?cellular and solu%le@ .ok sepsis dihu%un/kan den/an kontrol kesehatan K 5ampak pada sur&i&ors dan non)sur&i&ors pada 28 hari. and chornic health e&aluation9 c>RP: calcitonin /ene)related peptide9 #O: hi/h)molecular 'ei/ht kinino/en.1=0< :itric o4ide ?:$@.siolo/.1=4.18A< Protein !)100% . Clinical stud.. C.s. Clinical stud.P@ . and chronic health e&aluation9 0 >Q: monoeth.s %efore death@ .18=< :! .nthase ?CP!@)1 .!tudi klinis den/an kuran/ dari 20 patients9 -. -.cine4. score C?m@ " K K 0emprediksi respon dari terapi -erhu%un/an den/an !"P! . nitrite .G@ . pasien %edah saBa9 ?m@.186< 0 >Q test . .5a%le =: -iomarkers related to &aosdilation identified in the literature search ?'ith some selected references@ ?Continued@ 47 kD #O . . !tudi klinis den/an le%ih dari 50 pasien9 ?s@. sur/ical patients onl.siolo/.siolo/.dro%iopterin . 5a%le 7 -iomarkers dari d.184.1A1.l phosphate s. ..9 ?m@. Clinical stud.174)177< Giltera%le cardiodepressant su%stance ?GC!@ . "P"C# : acute ph.188< Pre . %erhu%un/an den/an !$G" score &aluasi se%a/ai pro/nostis K+ K++ Oomentar "trial natriuretic peptide ?":P@ .187. "P"C# : acute ph. of less than A0L9 ".1=5< Vasoacti&e intestinal peptide ?V.)enhancin/ factor ?P.176< ndothelin)1 and pro)endothelin) 1 .1=A< -rain natriuretic peptide ?-:P@ ..158< :europeptide P . medical pasien saBa . %erhu%un/an den/an "P"C# .cell colon.lidide9 0$G: multiple or/an failure9 :! : neuron)specific enolase9 !"P!: simplified acute ph. controls Predicted de&elopment of septic shock Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.. score9 !$G": seMuential or/an failure assessment.170)172< Car%om.181< #epatoc.1=1. nitrate. medical patients onl.185< 0. of sepsis . D@ . !tudi klinis den/an 20sampai 50 patients9 C.1=2< !u%stance P .180< alpha /lutathione !)transferase ?>!5@ . %erhu%un/an den/an !$G" score 0enin/kat pada sepsis di%andin/kan d e n / a n kontrol kesehatan 5ampak di antara sur&i&ors dan non)sur&i&ors pada 28 diidentifikasi dari literatur ?den/an referensi pilihan@ !epsis marker !udah uBi e4perimental &aluasi studi klinis C K K K C?s@ K K K K K " K K " K K 0enin/kat pada sepsi di%andin/kan den/an 'ith kontrol kesehatan 5ampak den/an sur&i&ors dan non)sur&i&ors pada 28 hari.178< >c)/lo%ulin .ncreased in sepsis compared 'ith health.15=.187< Pancreatitis)associated protein).1=7< K " " +sensiti&it. in the late phase of sepsis. %erhu%un/an "P"C# . 'ith more than 50 patients9 ?s@.17A< >lial fi%rillar.1==.

dia/nosis of sepsis9 fi&e of these had reported sensiti&it... phospholipase 2 ?P*"2). 5he sensiti&it.t is important to emphasiNe that culture)positi&e sepsis 'as /enerall. response due to other causes. necrotiNin/ enterocolitis .206< *ipopol. ill adult patients 'ithin 24 hours after admission . >roup . .. the P.@ .200< "lpha1)acid /l. arl. *. and specificit.207< -erhu%un/an den/an CRP pada pasien de n/a n s. of stratif.coprotein . this is not an a%solute rule %ecause some sepsis %iomarkers failed to ha&e pro/nostic &alue . "dditionall. and specificit.saccharide %indin/ protein ?*-P@ .5a%le 8 -iomarkers protein fase akut diidentifikasi dari pencarian literatur ?den/an referensi@ !epsis 0arker &aluasi pada studi e4perimental K &aluasi pada studi klinis -?s@ " C -?m@ K K K C?s@ C C K K+ K &aluasi se%a/ai faktor pro/nosis K K K+ K K Oomentar !erum am..2 n//ml@ . and spe) cificit. an. and specificit. %erhu%un/an den/an !$G" 0enin/kat pada sepsis score %erhu%un/an den/an uBi kesehatan dan pasien den/an >>O 0enin/kat pada sepsis di%andin/kan den/an tidak sepsi 0enin/kat pada infeksi di%andin/ d e n / a n pasien non)infeksi 5ampak antara sur&i&ors dan non)sur&i&ors pada 28 hari.R$ model has %een proposed as a 'a. "P"C# : acute ph. for the earl. score +sensiti&itas dan specificitas kuran/ dari A0L9 ".nfection. 5hese t'o %iomarkers ha&e not %een e&aluated for this purpose in adults.*)12 'as measured in ne'%orns at the time 'hen sepsis 'as first suspected clinicall.11.!" assa. or local infection from s. some of the proposed pro/nostic mar) kers. :eu) trophil CD11% could distin/uish septic pediatric patients from those 'ith possi%le infection 'ith /ood sensiti&it. and the de/ree of $r/an d.205< Pentra4in 6 .66<. . the response to therap.loid " ?!""@ . s. CD=4 had hi/h sensiti&it. of the other 11 %iomarkers used to dia/nose earl.20<.ndrome from an inflammator. 5ampak antara sur&i&ors dan non)sur&i&ors pada 28 hari.65<9 and fi%rin de/radation products ?100L for >ram)ne/ati&e sepsis %. is associated 'ith impro&ed outcomes. to differenti) ate patients due to sepsis.20=. -iomarkers can %e more useful to rule out sepsis than to rule it in. pasien medis saBa.202< #epcidin .s) function .1AA< Gerritin . s ensiti&it.1A4.ok sepsis Prediksi disfun/si hati pada pasien de n /a n sepsis Prediksi response terhadap therap. !tudi k l i n i s den/an R50 pasien9 ?s@.P)10@ 'as hi/her in neonates 'ith sepsis and necrotiNin/ enterocolitis than in neonates 'ho had onl.2A<.. to predict 'hich patients 'ere at /reater risk of d. . institution of appropriate therap. of more than A0L.1A8. dia/nosis of sepsis is also an important issue as earl.1A=. and specificit.60<.1A7< C)reacti&e protein ?CRP@ .siolo/. 5he maBorit. 1e iden) tified 1= factors that ha&e %een e&aluated specificall. and chronic health e&aluation9 !$G": seMuential or/an failure assessment.204< Procalcitonin ..@ 'as reported to ha&e hi/h sensiti&it.67)6A<. and specificit. .64<9 acti&ated partial throm%oplastin time ?aP55@ 'a&eform ?A=L@ .ndeed. to die. %erhu%un/an den/an !$G" score 5ampak antara sur&i&ors and non)sur&i&or spa da 28 hari.6A. sepsis 'ere not reported or 'ere less than A0L. dia/nosis of sepsis in adults.1A5< Ceruloplasmin . of or/an failure has a si/nifi) cant impact on the pro/nosis of patients 'ith sepsis. . and specificit.t is kno'n that the e4tent of infection and the se&erit. includin/ anti) %iotics.164.nterferon)induced pro) tein 10 ?. patients 'ith sepsis. Pasien %edah saBa9 ?m@. %erhu%un/an den/an "P"C# . 'ere tested in onl. !tudi k l i n i s den/an 20 sampai 50 patients9 C. .stemic sepsis . to sur&i&e from those likel.6=<. &aries amon/ patients.21. 0oreo&er. and none had sufficient ?more than A0L@ sensiti&) it. . %iomarker is e4pected to ha&e some pro/) nostic &alue and sepsis %iomarkers are no e4ception9 ho'e&er. for the earl.n the future. of the %iomarkers that 'e identified in our search 'ere assessed for their a%ilit.. %ut could not relia%l.62<.in/ septic patients accordin/ to their Predisposin/ condition. the Response to therap. contri%ute to this model of classification rather than Bust %ein/ used as pro/nostic markers. sepsis %iomarkers ma. 1e identified three %iomarkers 'ith hi/h ne/ati&e predicti&e &alue to rule out sepsis: PC5 ?AAL at a cut)off &alue of 0. of .201. althou/h cultures ma. remain ne/ati&e in man. to predict the de&elop) ment of multiple or/an failure and t o e &aluate response to therap. used as the /old standard in all these studies. . the se&erit.61<. for the dia/nosis of %acteremia in criticall. Clinical studi kuran/ dari 20 pasien9 -. distin/uish &iral from %acterial infec) tions. Recentl. and 'as hi/her in patients 'ith sep) sis than in those 'ithout . $ther %iomarkers 'ere assessed for their a%ilit.

222.ncreased in sepsis compared 'ith health.268< >hrelin . score in patients 'ith se&ere sepsis .60< *actate .s K K K K K++ K K Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. predicted response to therap.. predicted polon/ed .s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.226< Dipeptid.210< "polipoprotein C. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.26=.218< Complement ?C6.24=< #2! . correlation 'ith !"P! .260. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.5a%le A $ther %iomarkers identified in the literature search ?'ith some selected references@ !epsis marker &aluated in e4perimental studies K K " C " " C -?m@ K K C "?s@ C?s@ C " -?m@ " -?s@ K K C?s@ C C?m@ K K K++ K+ K Correlated 'ith "P"C# . acid amide h.ncreased in sepsis compared 'ith health.241< #eat shock protein ?#!P@70.s in patients 'ith se&ere sepsis Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.ntracellular nitric o4ide in leukoc.p@ .227< lastase .aluronan . .264< Gree D:" .220< 5erminal complement comple4 .P)10 .nter)alpha inhi%itor proteins ?.265< >)C!G and >0)C!G .s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. correlated 'ith !$G" score .psin comple4 .te .s.tic .1A=.208< "l%umin .21A.224< Diiodot.s in patients 'ith septic shock.240< >ro'th arrest specific protein ?>as@ = .250< . .CE len/th of sta.248.s.267< >elsolin .22A< lastase)a1)antitr.256. predicted response to therap.214< -eta)throm%o/lo%ulin .ncreased in septic shock compared 'ith health. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.228.lpeptidase . 76. Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s. correlated 'ith lactate le&els .217< Cholesterol ..ncreased in sepsis compared 'ith non)septic criticall. correlated 'ith !$G" score Decreased in sepsis compared 'ith health. Predicted response to therap.ncreased in infected dia%etic patients compared 'ith non) infected dia%etics Decreased in sepsis compared 'ith health.s in patients 'ith septic shock Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.247< #.alpha.rosine ?D.242)245< #D* cholesterol #*")>5 protein ?solu%le@ .s in patients 'ith septic shock Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s Predicted response to therap.21=< Ceramide .221< Dendritic cell . 72.s./> anti%odies .262< G2 isoprostanes .266< Gatt.254< K K K K K K K K K K+ K++ K C C C K K K K .thropoietin . Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.215< Caspase)1 .225< icosanoid .261< r.5@ . in patients 'ith Boint infections Predicted response to therap. controls .24A< #.s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. C4.drolase .20A< "nti)endoto4in core anti%odies ? ndoCa%@ . K Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.252< . score Predicted de&elopment of 0$G :e/ati&el.251< . ill Correlated 'ith !"P! score.211)216< -cl)2 . controls Predicted de&elopment of 0$G Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s &aluated in clinical studies &aluated as a pro/nostic factor Comment "lpha2 macro/lo%ulin . C5a le&els@ .drol.26A. A0 and 62 .22=.

clini) cal practice. score in patients 'ith se&ere sepsis Correlation 'ith "P"C# .281< Eric acid .28=< K K C?s@ -?s@ K K " C -?s@ K " C C C "?m@ " K K -?m@ "?m@ K C?s@ C " K -?s@ C K K K Decreased in postoperati&e patients 'ith sepsis compared 'ith those 'ith no sepsis Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. esta%lished itself suffi) cientl.2=2< :G) . controls . score9 !$G": seMuential or/an failure assessment9 5.CE patients . . controls Predicted de&elopment of septic shock in neutropenic patients Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.siolo/ acti&it. controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.286< Erinar. and chronic health e&alution9 >)C!G: /ranuloc. controls Predicted de&elopment of 0$G Correlation 'ith lactate le&els in patients 'ith septic shock Correlation 'ith "P"C# .41<9 ho'e&er.280< 5.can .2==< Plasma amino acids .282< Erinar. 5he cost)effecti&eness of all these methods must also %e e&aluated.2=4< Peptido/l. score Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.2=5< Pl>G .@ . Clinical stud. Clinical stud.elinase ?enN.25A< 5. Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.s in patients 'ith se&ere sepsis.0P: tissue inhi%itor of metalloproteinase.65<. hi/her in septic than in non)septic . predicted de&elopment of 0$G .s. and e4pired@ . correlation 'ith "P"C# ..9 ?m@.2=1< :ociceptin/orphanin GS ?:/ $GS@ .ncreased in sepsis compared 'ith health.te)macropha/e colon.257< !erum l. stimulatin/ factor9 0$G: multiple or/an failure9 :G) -: nuclear factor kappa -9 Pl>G: placental /ro'th factor9 !"P!: simplified acute ph.5a%le A: $ther %iomarkers identified in the literature search ?'ith some selected references@ ?Continued@ *actoferrin . %e interestin/ to com%ine se&eral %iomarkers .275< !erum %icar%onate . and e4pression@ .ncreased in sepsis compared 'ith health.da.272< Resistin . 8)$hd> .s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.. it ma.274< !elenoprotein P .27A. :o %iomarker has.s . of less than A0L9 "..277< !ulfite .@ .255.. therefore.. Clinical stud.240. 'ith less than 20 patients9 -.276< !elenium .?acti&it.ncreased in sepsis compared 'ith health.25A< 0icroparticles ?cell deri&ed@ . controls Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.pothesis reMuires further stud. in patients 'ith se&ere sepsis Decraesed in sepsis compared 'ith health.s Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. controls K K Predicted response to therap. 'ith 20 to 50 patients9 C.. 'e tried to cate/oriNe the sepsis %iomar) kers accordin/ to their pathoph. "P"C# : acute ph. to %e of /reat help to clinicians in e&er. of the aP55 'a&eform in the dia/nosis of sepsis . "s each %iomarker has limited sensiti&it.252< :eurotensin .s Correlation 'ith "P"C# .s K K Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da. medical patients onl.siolo/ical role in sepsis.ncreased in se&ere sepsis compared 'ith health.s K K++ Distin/uished %et'een sur&i&ors and non)sur&i&ors at 28 da.40.2=7)2=A< Plasma fi%ronectin . and specificit.285< Qanthine o4idase ?acti&it. this h.258< 0atri4)metalloproteinase ?00P@)A . " clinical stud.278< 5ransformin/ /ro'th factor ?5>G@)%1 .siolo/.me acti&it.te colon.0P)1 and 2 .me ?enN. score . of more than A0L %ut specificit. %iliru%in o4idati&e meta%olites ?-$0s@ .2=0< :itrate e4cretion ?urinar.n this stud. :o pro/nostic &alue. !tudies usin/ panels of sepsis %iomarkers ha&e also pro&ided encoura/in/ results .s in patients 'ith se&ere sepsis Predicted response to therap..soN. correlation 'ith !$G" score K K K K K K K+ K +sensiti&it.)stimulatin/ factor9 >0)C!G: /ranuloc.42)44<. sho'ed that the com%ina) tion of aP55 'a&eform 'ith PC5 increased the specificit.s. 'ith more than 50 patients9 ?s@.ncreased in sepsis compared 'ith health.27=< !phin/om. and specificit.270< Plasmin alpha2)antiplasmin comple4 .271< Renin .2=6< :ucleosomes .25=< *eptin .284< "nne4in V %indin/ . sur/ical patients onl. . of less than A0L9 ++sensiti&it.0P)6 .@ .

to distin/uish %et'een &iral and %acterial infections Distin/uished %et'een sepsis and !. nitrate.R! Distin/uished %et'een %acteremic and non)%acteremic infections Distin/uished %et'een sepsis and or/an reBection in transplanted patients #i/her in septic patients compared 'ith those 'ith no sepsis arl. sur/ical patients onl.stemic inflammator.R! #i/her in patients 'ith sepsis and D.R! Distin/uished %et'een sepsis and !. dia/nosed pneumonia Dia/nosis of m.28A< 64 5roponin .=1< 1= .R! in neutropenic pediatric patients #i/her in septic shock compared 'ith cardio/enic shock Distin/uished %et'een sepsis and !.*)8+ .127< A )!electin ?cellular and solu%le@ .R! *o' sensiti&it. sin/le &alue9 c.C: disseminated intra&ascular coa/ulopath.. ?solu%le@+++ .241< 12 16 14 15 >)C!G .2A< 18 .te chemotactic protein9 :$: nitric o4ide9 P".9 ?m@. C.270< 2A P*"2).267< >elsolin . C4.@ .68< *-P .288.R! #i/her in septic patients compared 'ith patients 'ithout sepsis arl.287< Clinical stud. &alues o&er time.C compared 'ith no)septic patients 'ith D.258< 61 !52 ?solu%le@ .118< 2= Pentra4in 6 .65< CD11%+++ .saccharide)%indin/ protein9 0CP: of measurement c s s s s s c s s s s s c s s s s s s s s s s s s s c s s s s s s s $utcome #i/h ne/ati&e predicti&e &alue #i/her &alues in neonates 'ith sepsis than in those 'ith possi%le infection Distin/uished %et'een sepsis and !. more than A0L9 ".P: interferon)induced protein9 *-P: lipopol. of less than A0L9 +++sensiti&it.R! Dia/nosis of sepsis.*)18 . dia/nosis of sepsis %efore s. response s.60< *aminin .9 ": elastase alpha 1)proteinase inhi%itor9 *"0: endothelial leukoc. Clinical stud.12A< 8 ndocan .P)10+++ . dia/nosis of sepsis in ne'%orns Distin/uished %et'een Candida sepsis and %acterial sepsis Distin/uished %et'een >ram)positi&e sepsis and >ram)ne/ati&e Distin/uished %et'een sepsis and !.55< .61< 60 !erum l.sfunction in septic patients 5 Complement ?C6.ocardial d.21A< = " comple4 . distress s.ncreased in trauma patients 'ith sepsis compared 'ith no sepsis Distin/uished %et'een sepsis and !. of less than A0L9 ++sensiti&it. and specificit.66< CD25 . dia/nosis of "RD! in septic patients Distin/uished %et'een sepsis and !.can . medical patients onl.268< .: plasmino/en acti&ator inhi%itor9 pG:: plasma fi%ronectin9 P*"2: phospholipase "29 !.te colon.207< 27 Peptido/l. 'ith less than 20 patients9 -.108< 62 !urfactant protein ?".ndrome9 5R 0: tri//erin/ receptor e4pressed on m. nitrite .5a%le 10 -iomarkers that ha&e %een assessed for use in the dia/nosis of sepsis !epsis %iomarker 1 2 6 4 aP55++ .16=< 10 Gi%rin de/radation products .me acti&it.1A2< 66 5R 0)1 ?solu%le@ .mptoms in ne'%orns #i/her in septic neutropenic patients compared 'ith fe%ril neutropenic patients 'ithout sepsis #i/her in septic shock compared 'ith cardio/enic shock Dia/nosis of sepsis in pediatric patients Distin/uished %et'een >ram)positi&e and >ram)ne/ati&e sepsis.6=< 11 >as= .)stimulatin/ factor9 .me ?enN. of more than A0L %ut specificit.te adhesion molecule9 >)C!G: /ranuloc.62. and specificit. increased earlier than CRP . and specificit. Clinical stud. . -.*)1 receptor anta/onist .75< P".*)10 .R! #i/h ne/ati&e predicti&e &alue #i/her &alues in patients 'ith se&ere sepsis compared 'ith patients 'ith or/an failure %ut no sepsis Distin/uished %et'een sepsis and !. 'ith 20 to 50 patients9 C. C5a@ .87< CD=4+++ . C " C C C?s@ C -?s@ C C " C -?s@ C " C C C -?s@ " C 5.1A6< +sensiti&it. #i/her in trauma patients 'ith sepsis than in those 'ithout arl.1=1< $steopontin .2=2< 28 pG: .soN. 'ith more than 50 patients9 ?s@. Clinical stud.=5< 17 .R!.C Distin/uished %et'een septic shock and !.ndrome9 CRP: C)reacti&e protein9 D.)1 .R!: s.*)12+++ .=1< :$. aP55: acti&ated partial throm%oplastin time9 "RD!: acute respirator.70< 1A 20 21 22 26 24 25 . D@ .204< 0CP)1 .eloid cells.260< 7 *"0)1 ?cellular and solu%le@ .9 s.R! #i/her in postoperati&e patients 'ith infection compared 'ith no)infected postoperati&e patients Distin/uished %et'een sepsis and !.

nfect 2005. 5an/ -0. %ut none has suffi) cient specificit. ( mer/ 0ed 1AAA. 26:455)4=0. Pinsk. %ut this reMuires further e&aluation. Crit Care 0ed 200A.nfection 2008. -eale R. >erlach #. !a%ino #: C)reacti&e protein as a marker of infection in criticall.CEV. more for pro/nosis than for dia/nosis. 17. Gernandes ". Vincent (*: 5he time course of %lood C)reacti&e protein concentrations in relation to the response to initial antimicro%ial therap. 64:158A)15A=. :o%ori 5: fficac. Crit Care Clin 200=. 0aru. Crit Care 0ed 2008. >ullo ". $ntario.stemic inflammator. 0R: pidemiolo/. Uimmerman (*.9 . Reinhart O. Vender (!. 26. 0andra/os O. 1A:152)157. . 5akeda 5. >: 2001 !CC0/ !.sis. Run/atscher ". *ancet .ne -. Ramsa. Crit Care 0ed 1AAA.. Calandra 5. Gaist . 61:1767)1741.mplementation of the !ur&i&in/ !epsis Campai/n /uidelines for se&ere sepsis and septic shock: 'e could /o faster. Vincent (*: . 7:210)217. 0ealha R. also %e /uided %. Cook D. Carcillo (. 61:5A1. (. Uam%on 0. or sensiti&it. 2A:1606)1610. *uNNani ". Rantanen 5: *a%orator. Reinhart O: 0easures. !akurai #. *e 5ulNo P. 0arshall (C. Parrillo ( . and associated costs of care. 22. of se&ere sepsis in the Enited !tates: anal. emplo. =. to %e routinel. 8. 6=:216)21A.! .n &ie' of the comple4it.. 0arshall (C. . Oumar ". 0erlini ": Comparison of procalcitonin and C)reacti&e protein as markers of sepsis. *a&oue !. !il&a . . 5o'nsend !. !hock 200A. Crit Care 0ed 2001. -ohuon C. "n/us D. epidemiolo/. 67:22A0)22A8. 1ada #. . %e asso) ciated 'ith impro&ed outcomes . "nn "cad 0ed !in/apore 2008. Oumar R: -iomarkers of mild co/niti&e impairment and "lNheimerIs disease. 5oronto. 15. 17:101A)1025.ndrome. in patients 'ith sepsis. markers.45. -0( 2007. T Com%inations of se&eral %iomarkers ma.potension %efore initiation of effecti&e antimicro%ial therap. 12.4=<. Gisher C( (r. . 00. %ut this reMuires further e&aluation. 5he use of no&el therapies that modif. >. 2010 References 1. %ut it should also %e a%le to %e used to /uide therap. T :one has sufficient specificit. "%raham . Ranieri 0. ill patients. 20.C0/"CCP/"5!/!. !amii O: Procalcitonin and C)reacti&e protein durin/ the earl. =A:8A)A5. $lshaker (!: 5he C)reacti&e protein.t has %een sho'n that usin/ PC5 le&els to /uide therap. 0arshall (. and mediators: to'ard a sta/in/ s. 6. 14. :ishioka (. >ullo ".me)linked immunosor%ent assa. >iamarellos)-our%oulis (. 61:1250)125=. -run)-uisson C. " com%ination of se&eral sepsis %iomarkers ma. Vincent (*: !ur&i&in/ !epsis Campai/n: international /uidelines for mana/ement of se&ere sepsis and septic shock: 2008. reduces anti%iotic use and ma. Clermont >. *e&. phospholipase 29 5:G: tumor necrosis factor. used.siolo/. >acouin ". to %e routinel.siolo/ical pro) cess of sepsis ma. is under'a. 0ercan D. Competin/ interests 5he authors declare that the. Recei&ed: 10 (ul. #otchkiss R!. Parker 00. and dia/nosis. 0c*ean "!: "ccurac. 10. and treatment of sepsis. %e more effecti&e than sin/le %iomarkers. Dhainaut (G. 16. Clin Chem *a% 0ed 2000.P)10: interferon)induced protein 109 PC5: procalcitonin9 P*"2). DoriNNi R. %io) markers that can %e used in sepsis. dia/nosis of %acterial infections in a critical care unit. posttraumatic s.ntensi&e Care 0ed 1AA8. Voros D. Ramsa. of procalcitonin in the earl. -erlot >: 0ana/ement of se&ere sepsis and septic shock: challen/es and recommendations. . !uppes R. #ar&e. "n/us DC. 648:168)150. help to identif. 6=:2A=)627. 21. 5an/ -*. Goster D.sis of incidence. 0oreira P. CP and (*V 'rote the manuscript. that a sin/le ideal %iomar) ker 'ill e&er %e found. emplo.!": enN. : 5he pathoph.nternational !epsis Definitions Conference. Camus C. 24:185)188. PC5 and CRP ha&e %een most 'idel. "lmeida . Penttila . it is unlikel. 2010 Pu%lished: A Ge%ruar. douard "R. >urka D. 27:4A8)504. -iomarkers Definitions 1orkin/ >roup: -iomarkers and surro/ate endpoints: preferred definitions and conceptual frame'ork. ( Crit Care 2008.ed in clinical practice. 1ood O .n the future. Vincent (*. Clin 0icro%iol . "n/us DC./o& identifier :C50068=425@. -ianco :. Chean/ 0: Duration of h. 200A Re&ised: 28 Decem%er 200A "ccepted: A Ge%ruar. Ro%erts D.. 11. 2000. 11:101)108. 67:40=)410. Pa&an R. " report of the Gifth 5oronto !epsis Roundta%le. >recka P. Ceola 0. Geuillu ". -enoist (G. 5ai%er/ *. 665:87A)886. Crit Care 0ed 2006. . >iannopoulou P..stematic re&ie' and meta) anal. Crai/ (C. 68:187)1A7. *e&er ". Ru%enfeld >. Polati . Oarl . Reinhart O: -iomarkers of sepsis. Canada. . *e&. CP conducted the literature search. "uthorsI contri%utions CP and (*V concei&ed the stud. "ssicot 0. 0atsushima P. 5hompson -5. the pathoph. Conclusions $ur literature re&ie' indicates that there are man. Crit Care 0ed 200=. conditions or to predict outcome. 18. Cl.: !epsis: definition. %ut e&en these ha&e limited a%ilities to dis) tin/uish sepsis from other inflammator.stem for clinical sepsis.48<. response s. *idicker (. $pal !0.: /roup . !e&ransk. or sensiti&it. Coelho *. to e&aluate the &alue of protein C le&els to /uide the administration of acti&ated protein C ?clinicaltrials. !uprin . Vincent (*: Procalcitonin used as a marker of infection in the intensi&e care unit. A. Po&oa P. 5homas R: Procalcitonin: a &alua%le indicator of infection in a medical . sepsis %iomarkers ma. #atada 5. Cook D(.keBiri 0. 0ackenNie . 2=:1262)1268. Carlet (0. help us administer these thera) pies to the ri/ht patient at the ri/ht time. $cto%er 25)2=. E/arte #. 0arshall (C. ( Crit Care 2004. *inde)U'ir%le 15. Oe. Gink 0P. 4. 7.stemic inflammator. "lmeida)de)Castro R. Cohen (. response s. Crit Care 0ed 2006. 0imoN $. 22:48A)501.ama O. is the critical determinant of sur&i&al in human septic shock. of the sepsis response. !chmit Q. !harma !. outcome. 2. 61:15=0)15=7.ed in clinical practice.ntensi&e Care 0ed 2000. -ion (.saBi !. Oumar ".. : n/l ( 0ed 2006. %iomarkers . or rule out sepsis. Crit Care 0ed 2006. Vincent (*. Penttila O. :akamura ". 1A. *i/ht -. . >iamarellou #: !hould procalcitonin %e introduced in the dia/nostic criteria for the s. dia/nosis of patients 'ith acute chest pain.*: interleukin9 . 00. messa/es T 0ore than 170 different %iomarkers ha&e %een assessed for potential use in sepsis.ndrome and sepsisV. Dellin/er RP. "%%re&iations aP55: acti&ated partial throm%oplastin time9 CRP: C)reacti&e protein9 *. " stud. 5. of procalcitonin for sepsis dia/nosis in criticall. 1=. slick >D. Geinstein D. ha&e no competin/ interests. ill patients: s. 0arini ((. Clin Pharmacol 5her 2001. de 0endonca ". Uanotti !." useful sepsis marker must not onl.nfect Dis 2007..47. %e more effecti&e. Gink 0P. 0. (aeschke R.

-oNNa G". de >root R: CC and CQC chemokine le&els in children 'ith menin/ococcal sepsis accuratel.*)=. 4A. PilmaN : !erum . Qia P#: . -runkhorst G: *ipopol.24. 4p 0ol Pathol 2002..smail 00. -artels #. Oimura #. De&iere (. 5ore $. !cheel 5. 1=8:2000)2007. 0arshall (C. 4=. #ermida (. #icklin >. -riel 0. 8A:A6)104. !asaki (.*)8 in septic patients. Piilonen ". 28. (ohnson D#. *ian/ QU. Ouster #. =6. !chneider EV. -irkhahn R. >raf (D. 2=. 0urch $. isen%er/ PR: le&ated concentrations of cross)linked fi%rin de/radation products in plasma. dia/nosis of neonatal sepsis 2 da. #el&aci !: &aluation of serum C)reacti&e protein. Pradier $. 11:R4A. 18:601)605. and interleukin)10 le&els as dia/nostic and pro/nostic parameters in patients 'ith communit. Van :uffelen 0. Pao #>. Chest 1AA6. "ndersson !. impro&ed 'a. 18:==8)=72. 0ueller -.stemic inflammation. Volk 5. /roup protein -1 in hepatic tissue 'ith the se&erit. "kalin #. -road%ent R. 1on/ RP. to detect infections. Van 0eter *. *aitinen . Do/an P. l. 0R. Da. and safet. tract infections in primar. predict mortalit. #elter%rand (D. 2A. and safet.P) 10 is an earl. :e&alainen 5(. "le/re 0. 6=. Rodri/ueN)1ilhelmi P. OonertN 1.C"0)1.. 644:=AA)70A. 25.nterleukin 1 receptor anta/onist and )selectin concentrations: a comparison in patients 'ith se&ere acute pancreatitis and se&ere sepsis.ntensi&e Care 0ed 1AA8. "l%ertson 5 . !epodes -. RaBamaki ". Clin Chem 200=. Chun/ O. 0R: . 5eoh *. ( Crit Care 1AAA. !un/urtekin #. -oNNa P5: C. : n/l ( 0ed 2001. !hock 2002. 0ate&ossian . Oaul 0. Chuan/ DP. ur ( Clin 0icro%iol .*)18 as an earl. of interleukin)12 and interleukin)10 in comparison 'ith other c. #ar%arth !. 0ac"rthur RD.tokine le&els in patients 'ith se&ere sepsis. Crit Care 2007. Dupont : !erum c. Uhon//uo 1ei Uhon/ -in/ (i (iu Pi Que 200=. 47. 48. #urtado V. ( . predicti&e indicator of lethal outcome. .sfunction. !im%runer >: . !her'in C. *opeN) Rodri/ueN ". 46. *i O.. =1. 126:2046)204A. 14:=6)=8. 81:160=)1608. "ika'a :: !erum 0. Chest 2006. and clinical course. Castro)Garia):eto #C. >urses . Poun/s D. -ota DP. Ruokonen : #0>-1 as a predictor of or/an d. =1:526)560. Uakariah ":. 0iller 0. Redl #. Curr $pin Pediatr 200=. Rohner P.R! and pulmonar. O. !hapiro :. Elm O. !child E. 5a%riNian 0: 5o'ard resol&in/ the challen/es of sepsis dia/nosis. Doi/ C: fficac. -r ( Pharmacol 200=.tokine profiles as markers of disease se&erit. Poun/ (. 41. 108: 12. #olNmann -: Differential re/ulation of s. Ourt ":. >. >omeN)*opeN *. Christ)Crain 0: Procalcitonin)/uided anti%iotic use &s a standard approach for acute respirator. Periat P. -ille (. *ancet 1AA8. !alluh (. Panacek ". multicenter deri&ation of a %iomarker panel to assess risk of or/an d. dia/nosis and mana/ement of neonatal sepsis. ".)onset neonatal sepsis. :/u. 66. Gischkoff !. 1illeitner " . and or/an failure in criticall. Vincent (*. "ittoniemi (. Carri/an !D. Gisher C( (r: fficac. Gerrer)Codina . "ssis G. G. Vincent (*: Com%ination of %iphasic transmittance 'a&eform 'ith %lood procalcitonin le&els for dia/nosis of sepsis in acutel.sfunction in rodent models of /ram)ne/ati&e and /ram)positi&e shock. 25:68A)6A4. 6=:2014)2022. 5hiemermann C: *. 0elot C.nflamm 2007. *emesho' !. 25:=2A)=6=. Relation to multiple) s. Detlefsen !. 1ei/hardt #. Oaptano/lu -: Esefulness of procalcitonin for dia/nosis of sepsis in the intensi&e care unit.ntensi&e Care 0ed 2008. *iaudat !. !tein/ru% (!. =2. 64:104=)1056.tes: a ne'. h. 58. d. #ensel 0.sis of Gc/ammaR. Gok 5G: . #amilton R>.. 628:18A)200.. procalcitonin. Pinsk. :/ PC. of the monoclonal anti)tumor necrosis factor anti%od. #eidecke CD. Chui O0.*@)8 and /ro'th related onco/ene)alpha in se&ere endoto4emia and the effects of a tumor necrosis factor)alpha/ . #. 0ota)Gilipe #. . *)selectin. -alc.ntern 0ed 2008. !0. >omes R:. 62:2176)2182. Oofoed O. #": 5he dia/nostic &alue of C)reacti&e protein. 7:85)A0. CoNNi !0.pes of sur/er. 67. *am #!: Dia/nostic markers for neonatal sepsis. $tero R.nterleukin = is a pro/nostic indicator of outcome in se&ere intra)a%dominal sepsis. 18:125)161. Pediatr Res 0. $s%orn 50.. VC"0)1. DiPiro (5. Car%onell) stran. !oares 0.*)18 and .stem or/an failure and mortalit. 177:4A8)505. 24:=80)=84. 0ontes R.lcholine reduces the or/an inBur. #ollander ( . -oNNa 05. 0oneer 00. !chick C. Gi/ueras)"lo. %ut pre&ents earl.*) 12 release durin/ postoperati&e sepsis: hi/h serum . 0ans%er/er "R (r: "ssociation of interleukin)4 plasma le&els 'ith traumatic inBur.nfect Dis 2001. 1on/ . l 0ahalla'. OanaNa'a 0. C.sophosphatid. !cott >. 0ontes 0. 5schirna D. 40. #eper P.pertension in pi/s. (ousela . l 0a/hra%. 0eisner 0. -r ( !ur/ 1AA4. !hinoNa'a P. :/o *. Chest 1AA6. 1orth (. Crit Care 0ed 2008. 0ilNman D. *aterre PG. and 5:G)alpha le&els in earl. ( Pediatr #ematol $ncol 2007. >oral >. 56. -archuk 15. Vincent (*. for sepsis %iomarkers usin/ 40"P technolo/. (eremias . and P)selectin le&els as markers of infection and their relation to clinical se&erit. !hao P0. department patients 'ith suspected sepsis. !hock 200=. :ikoskelainen (: arl. !uNuki 0. Chu 1C. !chuetN P.te chemotactic protein in risk stratification of fe%rile neutropenic children 'ith hematolo/ic mali/nancies. Clausi C0. 27..en #-. Rintala 0. 61. Oo4 1(: #. *aRosa !P.. 52:1284)12A6. Reinhart O. :o%re V. *opes)Gerreira G. (. -udak G. and monoc. tumor necrosis factor alpha. 5schaiko'sk. Valtonen 0. . 2A:161)16=. :uutila (. Vincent (*: C)reacti&e protein le&els correlate 'ith mortalit. !un/urtekin E. Deen O.stemic . D-. 65. 5rNeciak !. de OleiBn D. !hala%. =1:A6)A8. Oarlsson !. *aru)!ompa R.nninen 0. Daum *.sfunction and outcome in patients 'ith se&ere sepsis.s %efore clinical manifestation. 0istik R. 5akkunen $: . Oei/hle. 5=. 5A. #o'dieshell 5R. and pro/nosis of sepsis in rat<. 55. (ohnson !.nfusion of increasin/ doses of endoto4in induces pro/ressi&e acute lun/ inBur. Vermont C*. Dhainaut (G. *ilius 0: !imultaneous Muantitati&e anal. 60. *o%o !0. 24:661)668. 5roillet :: Esefulness of procalcitonin serum le&el for the dia/nosis of %acteremia. (imeneN)>onNaleN R: !erum solu%le . GuBishima !. %. 1eiss 0. Q. 10:R66. 45. -ernard >R. (ar&enpaa "*. in neonatal sepsis. 62./un "D. !chuttler (: Postoperati&e plasma concentrations of procalcitonin after different t.n&est 2001. Pettila V. 1u #P. *ipo'sk. 1ar'ick (. #ori !. 1. *0. and d. Crit Care 200=. Ellrich R: .P)1 alpha and . 160:115A)11=2.saccharide %indin/ protein in a sur/ical intensi&e care unit: a marker of sepsisV. =0. "nesthesiolo/.sis. dia/nostic marker for identification of late)onset %acterial infection in preterm infants.mmunol 0ethods 2007. Crit Care 0ed 2008. Ootilainen P. "m ( Perinatol 2007.*) 1%eta. Deitcher !R. 6A. "rch . !al&ia)Roi/es 0D.. Goster !(. Reith D: Etilit. Ouusela P. *eun/ 5G. (apiassu "0.. 64. identification of %acteremia %. /erer O.Relation %et'een le&el of e4pression of hi/h mo%ilit. 68. Oahn R(.er . 652:1271)1277. Ri&ers P: " prospecti&e. #aNelNet (". !cand ( Clin *a% ..pass. 20:524)527. >ermann P. interleukin)8. Oern G. shock. #ua CC. Pan/ C#: !erial c. >o. . >aieski DG. U%oBan (. 67:A=)104. :/ PC. 148:7=A)777.tokines and acute)phase reactants in the dia/nosis of neonatal sepsis. care.nninen 0. . 106:1107)1112.. . Poun/ !. >odekmerdan ". 0arkkanen #. Pediatrics 2001. "m ( Perinatol 2008.*)8. 5enhunen (. >ei/er R. 5akuma O. 6=:1507)1512.tokine le&els in human septic shock. Ourt ". !chmidhammer R. Do%%elsteen &an den >P. :ikoskelainen (. Cairns C-. 50. 42. Calla'a. Pu/in (: Ese of procalcitonin to shorten anti%iotic treatment duration in septic patients: a randomiNed trial. >ar%er > . G?a%I@2 fra/ment afelimoma% in patients 'ith se&ere sepsis and ele&ated interleukin)= le&els. in sepsis: a multiple4 anal. marker of /ram)ne/ati&e %acteremia. ill patients. 0ediators . and death in emer/enc. "n earl. 2007:616A7. u/en)$lsen (: De&elopment and &alidation of a multiple4 add)on assa. 0oretti . Patel R5.sfunction associated 'ith cardiopulmonar. -ur/ett E. "k/oN !. >oddard (O. >unnerson O(. "ndersen $. 0edlicott :(. 51.ntensi&e Care 0ed 1AA=. ill patients. 0cCaffre. #utNler ". . Crit Care 0ed 2004. *iu PC. Clin Chem 2004. !ie'ert (R. 0atsuka'a ". "m ( Respir Crit Care 0ed 2008. 44.perprocalcitonemia in patients 'ith noninfectious !. :upponen .)acMuired sepsis. 1assermann . Collin 0. Vaara 0. 76:220)22A. Oautiainen #. !akr P. ?CD=4@ e4pression on neutrophils and monoc. 106:5=5)575. "rch !ur/ 1AA5. $ral -. Repo #: :eutrophil CD11% e4pression and circulatin/ interleukin)8 as dia/nostic markers for earl.*)1%eta inhi%itor on these chemokines. pulmonar. *o%o GR. Rodri/ueN)0i/ueleN (0. :us%aumer C. :acul G . 1AA8. of recom%inant human acti&ated protein C for se&ere sepsis. #ohenthal E. Crit Care 0ed 200A. *aine !. (ordan)>arcia . #. 52.nterleukin ?. 57. mmanuilidis O.. -ucher #C. 22:11=A)1175. 50:1601)1614.nflamm Res . !oliman #0. Chen CO. 54. Crit Care 2006. Docke 1D. Rocha : . . PraN >. 5sen/ (C. and disease se&erit. %iochemical markers of s.nterleukin)1 receptor anta/onist and interleukin)= for earl.

. Ourimoto 0. #eidecke CD. !'iss)Dutch (5 . De Greitas . Van$tteren >0. $%erholNer ". #iraide #. Coopersmith C0. interleukin)1. "m ( Vet Res 2004. idhof #. !hock 2005. 0iller ((. #ack C : 0onoc. 5onnessen 5. 20:160)167. Colli/han :. 64:217=)2184. Papasteriades C. Ourosa'a !: Reduced neutrophil CD10 e4pression in nonhuman primates and humans after in &i&o challen/e 'ith . 5'i// 0.*)8: sensiti&e earl. in sepsis.lor G. Roussos C. 5akala ". markers of se&erit.*)12 production %efore sur/er. >old (": CD40 and CD80/8= act s. !cand ( . "ki%a O. 0atsuka'a ".nfect Dis 1AAA. >alle C.nterleukin)18 plasma le&els are increased in patients 'ith sepsis compared to se&erel. =A. -ohe (. %drup *. ( !ur/ Res 200=. Calandra 5.=4.(r. :a/ai 0.te)macropha/e colon. of patients 'ith se&ere communit. $rfanos ! . 12:285)2A1.. >rau > . Pan/ P. 82. 1oittieN "(.rosine kinase)1 in septic shock patients treated 'ith direct hemoperfusion 'ith a pol.te anti/en)DR e4pression predicts mortalit. Ootanidou ". 1==:2025)2062. 5hor/ersen -. Calandra 5..mmunol 2001.ama #. 5rentN $. Reinhart O. 174:1104)1110. solu%le CD1=6. Oron%or/ >: 0acropha/e serum markers in pneumococcal %acteremia: Prediction of sur&i&al %.ama . DouNinas : :eutrophil CD=4 e4pression and serum . Dimopoulou . in septic shock. 5 cells and plasma le&els of solu%le CD25. ( . !hock 2006. 0u 1. Chiocchetti ": !erum le&els of osteopontin are increased in !. #. 0ortiN ". Glierl 0.. 0aier !. A7. 5onnesen . ( Clin . >roup. Psarra ". 101. 1eiden 0. A8. 0onneret >.ner/isticall. Vandi&ier R1. Chest 2004. !cand ( . de *eiB *G: :eutrophil function capacit. 0ate&ossian . *aisne 0(. >oldman 0: Clinical and %iolo/ical si/nificance of interleukin)10 plasma le&els in patients 'ith septic shock. "rma/anidis ". #su 10. !u PC: " ne' model for outcome prediction in i ntra)a%d omi nal sepsi s %. Chesne. Oelse. 1hite !". Oro/ (.lor G (r. 1eiss D(. "m ( Respir Crit Care 0ed 2008. 6A:5A=)=06. >austad P. 5ack -G. $li&ieri C. 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Pharo ". (ohansen #5.te human leukoc. -rahm%hatt 5!. =5:5A)=6.(r. 5suBimoto #. de #aas 0. receptor and Gas/Gas*. 177:107)115.. !chrei%er #. "alto #. 162:4=)51. 1an/ C#. Voirin :. the increases in percenta/es of circulatin/ CD4WCD25W re/ulator. Oilds/aard (.tes from septic patients. A0. >iannoudis PV. 177:601)608. UiBlstra (>. 0ehta :. 76. #u%er)*an/ 0. #ira. Cholle. in 5A patients. Oinase'itN >5. 1etsel R": 4pression of the complement anaph. De >roote D. ( . -o//io . "ttermann (. 0artens ". 17A:16=)141. 26:6A)44. Rittirsch D. !uffredini "G: Detection of macropha/e inflammator. *epape ". Ounkel !*.saccharide. "nn !ur/ 2002. Griedman >. Venet G. 1illiams 0". !u P:.nfect Dis 1AA5.tes in infectious diseases: flo' c. -ra&o R: *P! do'n)re/ulates the e4pression of chemokine receptor CCR2 in mice and a%olishes macropha/e infiltration in acute inflammation. >uillou P(. Pounkin .mmunol 1AA8. >erauer O.mmunol 1AA5. Gosse . ( . =5:2=5)2=A. 154:1A00)1A08. "m ( Pathol 1AA7. 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Elm O. #akim ". 6=:286)2A0. 0arecau4 >.asaka O. 70. acMuired infection. !chellekens (. *ukacs :1. 5her "pher Dial 2008.lato4in C6a and C5a receptors on %ronchial epithelial and smooth muscle cells in models of sepsis and asthma. 0oller #(. 1=4:2768)2744. Crit Care 0ed 200=. 1=1:A82)A87. >emsa D. :ielsen #.sis of . 5hiN. 0eier)#ellmann ".nterleukin 16 and inflammator. se&ere sepsis. -riard C. A=. 1elle 0. =8.P)1%eta durin/ e4perimental endoto4emia and human sepsis. !u/imoto O.mmuno/lo%ulin !tud. Colom%o D. Van Damme (. :icola !. 114:220)227. in pol. :P.ashi :. GernandeN)!omoNa 0. Chan/ OC. 72. #sieh 1!. 5sao P:. -ohe (. correlate 'ith disease se&erit. #oshino !. -run #. 1esterholt ". !iitonen !. Chen CP. A6. ssenfeld)!ekler . Pierard >. Ourosa'a !: !epsis is characteriNed %. #oshi O. >raulet "0.sis of surface anti/en. and outcome in sepsis. tumor necrosis factor) alpha/tumor necrosis factor t. Ua%ner (. 0onneret >: 5he 5h2 response as monitored %. 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Vaschetto R.te chemotactic protein 1 is released durin/ lethal and su%lethal %acteremia in %a%oons. #sieh G(. *an #P. :a&alesi P. 17:2=6)2=8. >lauser 0P: Pro/nostic &alues of tumor necrosis factor/ cachectin. Oaneko !. !eki !.mphoc.mmunol 2000.nfect Dis 1AA0. Vanhems P: Persistin/ lo' monoc.*)16 in an e4perimental model of sepsis. to re/ulate inflammation and mortalit.

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Crit Care 0ed 2004. Go'ler "" . Pentti (. >lauser 0P. : . Crit Care 0ed 2005. 22:1568)154=. "-. Din/ C. :iimura 0.saccharide administration in &i&o. . 1halen 0(. &an Oessel OP.. -runner 0. Dimopoulou . -rade (. Pard -". #epatolo/. !akata P: !e&ere secondar.sfunction. 110. :ielsen #. D'orschak 0. $hmori 5. Choi !#. Choi #O. Pan !-. 60:A2)A7. >ro'th Gactors 2007. ur ( Pharmacol 2007. 114. procalcitonin. 120. $rfanos ! . 125. 1AA5. 5urner (. !eidelin (-. Ouhn D. Dou/ht. Ru%in D-. !hock 2004./>1 production in patients 'ith sepsis and trauma. Oochanek P0. 4=:6A8)404. Podesta (.ntensi&e Care 0ed 2004.

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"P)D@ le&els in patients 'ith septic "RD!. !uNuki !. 176:6065)6046. marker of acute lun/ inBur. *acks D. 201. 0ooiBaart !P. >urso. Clin .. >ao *.nflamm Res 1AAA. 10A:8=4)8=7. 150:126)160. !hock 1AAA. -achelet 0. response s. >l. 2A:2157)21=1.l/l. infection. 5raut'ein C.nada O. "m ( Respir Crit Care 0ed 1AA4. 1A7.)enhancin/ factor as a potential no&el %iomarker in acute lun/ inBur. "ntonucci "..durin/ porcine endoto4emic shock ma.ashi >.loid a protein in septic shock patients..tes./onin "". -ar%osa (".l *e'is?4@ /roups. &an Disseldorp . ndo !. 0ehta :(.. !eller)PereN >. sepsis. llis 0. !hoBi #. 2008:=61414. Pu P. A=:182A)1861. . !hipko&a 0.stemic inflammator. response in patients e4periencin/ endoto4emia follo'in/ electi&e cardiac sur/er. -(. 214. Couto RC.sfunction in septic patients 'ith pneumonia. 210. 1=4:68A)6A5. !imon -". >ietema (". 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0ostafa !0. !alto)5elleN 0. ( . -ohe (. Gamularo >. "naesth . 181:6558)65==. Proc :atl "cad !ci E!" 2005. 1A85. 62:1=67)1=42. ( ndoto4in Res 2007. !undM&ist O>. (or/ensen 5. -rueckmann 0: 0atri4)metalloproteinases and their inhi%itors are ele&ated in se&ere sepsis: pro/nostic &alue of 5. #offmann #: P0: elastase and leukoc. 5homas #. 0olda'er **.5@ in se&ere infections and sepsis: D. 1eerkamp "#.rosine ?D.tic elastase: an indicator of patho%iochemical alterations in septicemia after a%dominal sur/er. ratio of immature to total /ranuloc. Crit Care 0ed 2007. 24A. 1ada . 250. Pana/ihara .nt.saccharide)induced inflammation in the mouse.tic anti%odies correlate 'ith fa&ora%le outcome in sepsis. Vincent (*. Gai4 (D. Voirin :.nfect Dis 1A88. in se&ere sepsis patients: relationship to procalcitonin.te anti/en)>5 in septic shock: marked and persistin/ ele&ation as a predictor of sur&i&al. 252. 1illiams (P. 2=5.. ( Pediatr 1AA=. ( . -ertsch 5.t C .n Vi&o 200=.. -essman !. 248. 10:R=0. 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Van der 0R: :itric o4ide)deri&ed urinar. *ammle -. 5hompson (P. 1enstone R. eren%er/ "(.aluronan: relationship to hemod. 144:56=5)5671. 72:A45)A56. Palard. $&erturf >. 0ontiel C: Predicti&e &alue of nuclear factor kappa. 22A. PeBler >. CalieNi C. VelasMueN #!. -ohuon C: Decrease of serum dipeptid. 1an/ U(. 244.lpeptidase acti&it. 128:7=5)7=A. 0ori. Olaasen #*. Rios (. !otiropoulou C. (ochum 0. Ri&ers P.stemic inflammation and sepsis. !chears >. 5suchi. . 0onneret >. Cam)DucheN V. Vikerfors 5: . 240:4=5)471. Piliponsk. :a/araBa V. ill. "%rink 0. #aBi)0ichael P>. Puthuchear. :akahira O. c.ama O. >ehan -.on)!onsino D. Puchstein C. *aurent 5C. *enti *. #orn C. "0. 20:1615)1621.a P. (ones .0P)1 in se&ere sepsis. 0eta%olism 1AAA. 66:2540)254=. !ur/er. 5sai 0. Dus'ald O#. *aurent 5C. $fenstein (P. ( Crit Care 1AA7. 25A. Rosendahl 5. *im PP. 257. Rama/lia V. 256. !ir. !himiNu 5. 68:8=7)872. !chein R0. #offmann E. 6=:828)866. (aco%sen >. Crit Care 0ed 2005. 12:R10=. 241. 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