Current concept of abdominal sepsis: WSES position paper

MISSING IMAGE

Material Information

Title:
Current concept of abdominal sepsis: WSES position paper
Physical Description:
Mixed Material
Language:
English
Creator:
Sartelli, Massimo
Catena, Fausto
Saverio, Salomone Di
Ansaloni, Luca
Publisher:
Bio-Med Central (World Journal of Emergency Surgery)
Publication Date:

Notes

Abstract:
Although sepsis is a systemic process, the pathophysiological cascade of events may vary from region to region. Abdominal sepsis represents the host’s systemic inflammatory response to bacterial peritonitis. It is associated with significant morbidity and mortality rates, and is the second most common cause of sepsis-related mortality in the intensive care unit. The review focuses on sepsis in the specific setting of severe peritonitis.
General Note:
Sartelli et al. World Journal of Emergency Surgery 2014, 9:22 http://www.wjes.org/content/9/1/22; Pages 1-16
General Note:
doi:10.1186/1749-7922-9-22 Cite this article as: Sartelli et al.: Current concept of abdominal sepsis: WSES position paper. World Journal of Emergency Surgery 2014 9:22.

Record Information

Source Institution:
University of Florida
Holding Location:
University of Florida
Rights Management:
All rights reserved by the source institution.
System ID:
AA00021876:00001


This item is only available as the following downloads:


Full Text

PAGE 1

REVIEWOpenAccessCurrentconceptofabdominalsepsis:WSES positionpaperMassimoSartelli1*,FaustoCatena2,SalomoneDiSaverio3,LucaAnsaloni4,MarkMalangoni5,ErnestEMoore6, FrederickAMoore7,RaoIvatury8,RaulCoimbra9,AriLeppaniemi10,WalterBiffl6,YoramKluger11,GustavoPFraga12, CarlosAOrdonez13,SanjayMarwah14,IgorGerych15,JaeGilLee16,CristianTran1,FedericoCoccolini4, FrancescoCorradetti17andJamesKirkby-Bott18AbstractAlthoughsepsisisasystemicprocess,thepathophysiologicalcascadeofeventsmayvaryfromregiontoregion. Abdominalsepsisrepresentsthehost ’ ssystemicinflammatoryresponsetobacterialperitonitis. Itisassociatedwithsignificantmorbidityandmortalityrates,andisthesecondmostcommoncauseofsepsis-related mortalityintheintensivecareunit. Thereviewfocusesonsepsisinthespecificsettingofsevereperitonitis.IntroductionAbdominalsepsisisassociatedwithsignificantmorbidity andmortalityrates. Resultsofprospectivetrialshaveoftenoverestimated theoutcomesofpatientswithsevereperitonitis[1].Treatmentofpatientswhohavecomplicatedintra-abdominal infections(IAIs)byadequatemanagement,hasgenerally beendescribedtoproducesatisfactoryresults;recentclinicaltrialshavedemonstratedanoverallmortalityof2%to 3%amongpatientswithcomplicatedIAIs[1,2]. However,resultsfrompublishedclinicaltrialsmaynot berepresentativeofthetruemorbidityandmortality ratesofsuchinfections.Patientswhohaveperforated appendicitisareusuallyoverrepresentedinclinicaltrials [1].Furthermorepatientswithintra-abdominalinfection enrolledinclinicaltrialshaveoftenanincreasedlikelihoodofcureandsurvival.Infacttrialeligibilitycriteria oftenrestricttheinclusionofpatientswithco-morbid diseasesthatwouldincreasethedeathrateofpatients withintra-abdominalinfections. Afterexcludingpatientswithperforatedappendicitis, Merlinoetal.[3]foundthatthecurerateamongpatients whohadintra-abdominalinfectionsandwereenrolledin clinicaltrials,wasmuchhigherthanthatofpatientswho werenotenrolled(79%versus41%)andthatthemortality ratewasmuchlower(10%versus33%). Epidemiologicalstudiesofpatientswithintra-abdominal infectionsincludingseverelyillsubjects,havedemonstratedhighermortalityrates[4]. IntheCIAOstudytheoverallmortalityratewas7.7% (166/2152)[5].Analyzingthesubgroupofpatientswith severesepsisorsepticshockatadmissiontohospital themortalityratereached32.4%(89/274).Inpatients withseveresepsisorsepticshockintheimmediatepostoperativeperiod,themortalityratewas42.3%(110/266). Abdominalsepsisrepresentsthehost ’ ssystemicinflammatoryresponsetobacterialoryeastperitonitis. Intheeventofperitonitisgram-negative,gram-positive, aswellasanaerobicbacteria,includingcommongutflora, suchas Escherichiacoli,Klebsiellapneumoniae Streptococcusspp. and Bacteroidesfragilis ,entertheperitoneal cavity.Sepsisfromanabdominaloriginisinitiatedbythe outermembranecomponentofgram-negativeorganisms (e.g.,lipopolysaccharide[LPS],lipidA,endotoxin)or gram-positiveorganisms(e.g.,lipoteichoicacid,peptidoglycan),aswellanaerobetoxins.Thisleadtothereleaseof proinflammatorycytokinessuchastumornecrosisfactor (TNF),andinterleukins1and6(IL-1,IL-6).TNFandinterleukinsleadtotheproductionoftoxicmediators, includingprostaglandins,leukotrienes,platelet-activating factor,andphospholipaseA2,thatdamagetheendothelial lining,leadingtoincreasedcapillaryleakage[6].Cytokines *Correspondence: massimosartelli@gmail.com1DepartmentofSurgery,MacerataHospital,Macerata,Italy Fulllistofauthorinformationisavailableattheendofthearticle WORLD JOURNAL OF EMERGENCY SURGERY 2014Sartellietal.;licenseeBioMedCentralLtd.ThisisanOpenAccessarticledistributedunderthetermsoftheCreative CommonsAttributionLicense(http://creativecommons.org/licenses/by/4.0),whichpermitsunrestricteduse,distribution,and reproductioninanymedium,providedtheoriginalworkisproperlycredited.TheCreativeCommonsPublicDomain Dedicationwaiver(http://creativecommons.org/publicdomain/zero/1.0/)appliestothedatamadeavailableinthisarticle, unlessotherwisestated.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22 http://www.wjes.org/content/9/1/22

PAGE 2

leadtotheproductionofadh esionmoleculesonendothelialcellsandneutrophils.Neu trophil-endothelialcellinteractionleadstofurtherendothelialinjurythroughthe releaseofneutrophilcomponents.Activatedneutrophils releasenitricoxide,apotentvasodilatorthatleadstoseptic shock.Cytokinesalsodisruptnaturalmodulatorsofcoagulationandinflammation,activatedproteinC(APC)and antithrombin.Asaresult,multipleorganfailuremayoccur. Earlydetectionandtimelytherapeuticintervention canimprovetheprognosisandoverallclinicaloutcome ofsepticpatients.However,earlydiagnosisofsepsiscan bedifficult;determiningwhichpatientspresentingwith signsofinfectionduringaninitialevaluation,docurrentlyhave,orwilllaterdevelopamoreseriousillnessis notaneasyorstraightforwardtask. Sepsisisacomplex,multifactorialsyndromewhich canevolveintoconditionsofvaryingseverity.Ifleft untreated,itmayleadtothefunctionalimpairmentof oneormorevitalorgansorsystems[7]. Severityofillnessandtheinherentmortalityriskescalatefromsepsis,throughseveresepsisandsepticshock upmulti-organfailure. Previousstudieshavedemonstratedthatmortality ratesincreasedramaticallyintheeventofseveresepsis andsepticshock[8].Severesepsismaybeareasonable approximationofthe “ tippingpoint ” betweenstableand criticalclinicalconditionsinthemanagementofintraabdominalinfections.Severesepsisisdefinedassepsis associatedwithatleastoneacuteorgandysfunction, hypoperfusion,orhypotension. Itiswellknownthathypotensionisassociatedwithan increasedriskofsuddenandunexpecteddeathinpatients admittedtohospitalwithnontraumaticdiseases[9]; identifyingpatientswithseveresepsisearlyandcorrecting theunderlyingmicrovasculardysfunctionmayimprove patientoutcomes.Ifnotcorrected,microvasculardysfunctioncanleadtoglobaltissuehypoxia,directtissuedamage,andultimately,organfailure[10]. TheSurvivingSepsisCampaigninternationalguidelines formanagementofseveresepsisandsepticshockwere recentlyupdated[11].Theseguidelinesarethecornerstoneforthemanagementofseveresepsisandseptic shock,buttheydonotfocusonthespecificsettingof intra-abdominalinfections. Althoughsepsisisasystemicprocess,thepathophysiologicalcascademayvaryfromorgantoorgan. Therearefewdataregardingsystemicandlocalresponsesduringperitonitisinhumansandontheircorrelation topatientsoutcomes[12-14]. Basedonfindingsofhighconcentrationsofcytokinesin theperitonealcompartment,someevidencessuggested thatintra-abdominalsepsismayresultinacytokinemediatedinflammatoryresponsethatisinitiallycompartmentalizedintheperitonealcavity[15,16]. Animalmodelshaveshownthatperitonitisisassociated withasignificantandprolongedperitonealinflammatory responsewhichisadverselycorrelatedwithsurvivaloutcome[17]. Thelevelsofselectedperitonealcytokineshavebeen reportedtobesignificantlydifferentbetweenanimals thatsurvivedascomparedtothosewhodiedfollowinga septicchallenge[18]. Plausibilityofperitonealcompartmentalizationofinitial inflammatoryresponseduringperitonitiswashighlighted byarecentprospectivecohortstudyofpatientswithsecondarygeneralizedperitonitis[19].ItconfirmedthatIL-1, TNF ,IL-6,IL-10andIFN arepresentathighconcentrationsintheperitonealfluidofpatientswithperitonitis. Theresultsofthisstudyshowedalargegradientbetween peritonealfluidandplasmaconcentrationsofcytokines, withnocorrelationbetweenperitonealandplasmalevels, suggestingthatplasmalevelsmayincreaseonlyaftersaturationoftissueswithintheabdominalcompartment. Theinflammatoryresponseinpatientswithsepsis dependsonthecausativepathogenandthehost(genetic characteristicsandcoexistingillnesses),withdifferential responsesatlocal,regional,andsystemiclevels[20]. Thehostinflammatoryresponseprobablychanges overtimeinparallelwiththeclinicalcourse.Sepsis,in theearlystagesoftheinflammatoryprocess,shouldbe consideredasalocal/peritonealdisease.Inadvanced stages,severesepsisandsepticshockshouldbeconsideredasasystemicdisease,andpatientswhoareextremely unstableandexhibithighratesofmortalityshouldbe managedmoreaggressively. Incertainpatientsperitonitiscanquicklyleadtoan excessiveinflammatoryresponse,andearlyandaggressive mechanicalperitonealcontrolisdeterminantforstopping thesepticprocess.Inthosepatientsinabilitytocontrolor interruptthelocalinflammatoryresponseisassociated withpooroutcomes. Inpatientswithongoingsepsis,severallaparotomies mayberequired.Underthesecircumstances,openabdomenallowsthesurgeontoperformsubsequentlaparotomiesmoreefficientlyandpreventtheonsetofabdominal compartmentsyndromethatmayfurtherworsenthe systemicdisease. Thereviewfocusesonmanagementofpatientswith severesepsisorsepticshockinthespecificsettingof severeperitonitis.DiagnosisReducingtimetodiagnosisofseveresepsisisthoughtto beacriticalcomponentinreducingmortalityfrom sepsis-relatedmultipleorgandysfunction[11].Delineatingthesourceofinfectionasaccuratelyaspossibleprior tosurgeryistheprimaryaimandthefirststepinmanagingintra-abdominalinfections.InsevereabdominalSartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page2of16 http://www.wjes.org/content/9/1/22

PAGE 3

sepsishowever,delaysinoperativemanagementmay leadtoworseoutcomesandearlyexplorationisalways recommendedwhenperitonitisissuspectedevenifthe sourceofinfectionisnotrecognizedpre-operatively withcertainty. Thediagnosisofintra-abdominalsepsisisbasedprimarilyonclinicalassessment.Typically,thepatientisadmittedtotheemergencydepartmentwithabdominalpain andasystemicinflammatoryresponse,includingfever, tachycardia,andtachypnoea.Abdominalrigiditysuggests thepresenceofperitonitis.However,clinicalassessment aloneisnotalwaysreliableincriticallyillpatientsduetoa varietyofclinicalconstraints(e.g.,impairedconsciousness, severeunderlyingdisease,etc.).Hypotension,oliguria,and acutealteredmentalstatusarewaringsignsofthepatient ’ stransitionfromsepsistoseveresepsis. Plainabdominalfilmsareoftenthefirstimaging obtainedforpatientspresentingwithperitonitis.Upright filmsareusefulforidentifyingfreeairunderthediaphragm(mostoftenontherightside),whichcanresult fromperforatedviscera.Freeairmaybepresentinmost casesofanteriorgastricandduodenalperforation.Howeveritismuchlessfrequentwithperforationsofthesmall bowelandcolonandisunusualwithappendicealperforation.Abdominalplainfilmshavelowsensitivityand specificity,andhave,inmostcases,beenreplacedby abdominalcomputedtomography(CT).However,plain filmsoftheabdomenremainareasonableinitialstudyfor patientswithsuspectedperitonitiswho,onthebasisof historyandphysicalexamination,arelikelycandidatesfor surgicalexploration.Inthiscase,abdominalplainfilms mayconfirmevidenceofperforationinshorttime. Ultrasonographyandcomputedtomographyhavebecomeessentialdiagnostictoolsinabdominalsepsis.The diagnosticapproachtoconfirmthesourceofabdominal infectioninsepticpatientsdependslargelyonthehaemodynamicstabilityofthepatient[21]. Criticallyillpatientswhoarehaemodynamicallyunstableorhavedevelopedsevereacuterespiratorydistress syndrome(ARDS)requiringhigh-levelventilatorysupport,areatsignificantriskduringtransporttotheradiologydepartmentInunstablepatientswhodonot undergoanimmediatelaparotomyandwhosecritical conditionpreventsthemfromleavingICUforfurther imaging,ultrasound(US)isthebestavailableimaging modality[22].Itisportable,itcanbeperformedatthe bedside,itisreproducibleandcanbeeasilyrepeated. Majordrawbacksareileusandobesity,whichmay significantlymasktheUSview.USisalsostrongly operator-dependent.InsuspectedbiliarysepsisUSis alwaysthepreferredinitialdiagnosticmodalityfor acutecholecystitisandemphysematouscholecystitis. Instablepatients,abdominalcomputerizedtomography(CT)istheimagingmodalityofchoice,especially whenthediagnosisisuncertain.However,inpatients withseveresepsis,ifthediagnosisofperitonitisismade clinicallyorbypreviousradiologicalexaminations(plain filmsoftheabdomenorUS),additionalCTscanning maybeunnecessaryandwouldonlydelaymuch-needed surgicalintervention[22]. Anotheroptioninthediagnosisofcriticallyillpatients sufferingfromintra-abdominalsepsisisbedsidelaparoscopy,asitcanavoidpatienttransporttotheradiological departmentoroperatingroomisveryaccurate,and maintainsICUmonitoring[23].Laparoscopyprovidesa “ minimallyinvasive ” definitivemodalitytodiagnose intra-abdominalsepsis.Itmayquicklyprovidethenecessaryinformationtoaddressfurthermanagement.However, theoverallmortalityofpatientsundergoingdiagnostic laparoscopyintheICUishigh,regardlessofdiagnostic findingsduringthisprocedure.Theuseofdiagnosticlaparoscopyshouldbelimitedtopatientsinwhomatherapeutic interventionisstronglysuspected[24].AntimicrobialtherapyAkeycomponentofthefirst-linemanagementofthe septicpatientistheadministrationofIVantimicrobial therapy.Antimicrobialtherapyplaysapivotalroleinthe managementofintra-abdominalinfections,especiallyin patientswithseveresepsiswhorequireimmediateempiricantibiotictherapy. Aninsufficientorotherwiseinadequateantimicrobial regimenisoneofthevariablesmorestronglyassociated withunfavorableoutcomesincriticalillpatients[25]. Empiricantimicrobialtherapyshouldbestartedassoon aspossibleinpatientswithseveresepsiswithorwithout septicshock[26-28]. AprospectiveobservationalstudybyRichetal.involving180patientswithsecondarygeneralizedperitonitis, reportedsignificantlyhighermortalityratesinpatients presentingwithsepticshock(35%)comparedtothose presentingwithoutit(8%)[29]. Theroleoftheinfectingpathogenonthepatients responseinsecondaryperitonitishasbeenpoorly investigated. Someauthorssupporttheconceptofa ‘ genericseptic response ’ inwhichanidenticalimmuneresponseistriggeredbyanytypeofbacteria[30,31]. Contrastingly,otherssuggestthatdifferenttypesof pathogensmayelicitvariousinflammatoryresponses, despiteacommonpathwayofactivation. Richeetal.havefoundthatpolymicrobialculturesor anaerobesintheperitonealfluidwereassociatedwith morefrequentsepticshock[29]. Arecentprospectivecohortstudyshowedthat patientsinwhomanaerobesor Enterococcus species [19]wereisolatedfromperitonealfluidculturesreleased moreTNF intheirplasmathanthosewhowereinfectedSartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page3of16 http://www.wjes.org/content/9/1/22

PAGE 4

withotherstrains.Thehypothesisthatdifferenttypesof pathogensmayelicitvariousinflammatoryresponses, wasalreadyhighlightedinanimalmodels.Inratswith peritonitis,Montravers etal .showedthatadjunction of Enterococcusfaecalis wasassociatedwithincreased mortalityaswellashigherlevelsofTNF andIL-6 inperitonealfluid[32,33]. Evidenceregardingaspecificroleofsomepathogens onthepatternofthesepsisresponseisrathersmall,preventinganydefinitiveconclusionfromtheseresults. Howeveritiswellknownthatpatientswithsevere sepsisorsepticshockmaybenefitfromaggressiveantimicrobialtreatmentinordertocurbthespreadof themultipleorgandysfunctionsyndromecausedby anongoingperitonealtrigger. Forthesepatients,ade-escalatedapproachmaybethe mostappropriatestrategy.Increasingratesofresistance andamorecomprehensiveunderstandingofthesepsis processhavepromptedmanyexpertstoadvocatethe useofbroad-spectrumantimicrobialregimensinthe initialstagesoftreatmentforsepsis[34,35].Subsequent modification(de-escalation)oftheinitialregimenbecomespossiblelater,whencultureresultsareavailable andclinicalstatuscanbebetterassessed,48 – 72hours afterinitiationofempirictherapy. Whentreatingabdominalsepsis,cliniciansmustbe awarethatdrugpharmacokineticsmaydiffersignificantly betweenpatientsduetothevariablepathophysiologyof sepsis,andmustalsotakeintoaccountthepathophysiologicalandimmunologicalstatusofthepatient[36]. The “ dilutioneffect ” ,alsocalledthe ‘ thirdspacing ’ phenomenon,mustbeconsideredwhenadministering hydrophilicagentssuchas -lactams,aminoglycosides, andglycopeptides,whichselectivelydistributetothe extracellularspace.Lowplasmaantimicrobiallevelscan contributetolowerthanexpectedantimicrobialconcentrationsinperitonealfluidwithpotentiallyreduced antimicrobialdeliverytothetargettissues.Infact,the targetplasmaconcentration(Ct)thatshouldbeachieved withtheloadingdose(LD)dependssolelyonthevolume ofdistribution(Vd)ofthedrug(LD=CtVd).IftheVd isenlargedtheCtwillresultsinalowerthanexpected levelwiththestandardLD[36]. Higherthanstandardloadingdosesof -lactams, aminoglycosides,orglycope ptidesshouldbeadministeredtoensureoptimaldrugexposuretotheinfectionsiteinpatientswithseveresepsisorseptic shock[36]. Lastlyitshouldbekeptinmindthattheloadingdose oflipophilicantibiotics(Macrolides,Fluoroquinolones, Tetracyclines,Chloramphenicol,Rifampicin,Linezolid) whicharenotinfluencedbythe “ diluitioneffect ” ,should notbeinfluencedbytheseveresepsisorsepticshock status[36]. Onceappropriateinitialloadingisachieved,itis mandatorytoreassesstheantimicrobialregimendaily, becausethepathophysiologicalchangesthatmayoccur, maysignificantlyaffectdrugdispositioninthecritically illpatients.Lowerthanstandarddosagesofrenallyexcreteddrugsmustbeadministeredinthepresenceof impairedrenalfunction,whilehigherthanstandarddosagesofrenallyexcreteddrugsmaybeneededforoptimal exposureinpatientswithglomerularhyperfiltration[36]. InTable1recommendeddosingregimensofthemost frequentlyusedrenallyexcretedantimicrobialsaccordingtorenalfunctionareillustrated. Table1Recommendeddosingregimensofthemostfrequentlyusedrenallyexcretedantimicrobialsaccordingtorenal function[21]Renalfunction AntibioticIncreasedNormalModeratelyimpairedSeverelyimpaired Piperacillin/ tazobatam 16/2gq24hCIor3.375 q6hEIover4hours 4/0.5gq6h3/0.375gq6h2/0.25gq6h Imipenem500mgq4hor250mgq3h over3hoursCI 500mgq6h250mgq6h250mgq12h Meropenem1gq6hover6hoursCI500mgq6h250mgq6h250mgq12h ErtapenemND1gq24h1gq24h500mgq24h Gentamycin9to10mg/kgq24hb7mg/kgq24h7mg/kgq36 – 48h7mg/kgq48 – 96h Amikacin20mg/kgq24h15mg/kgq24h15mg/kgq36 – 48hb15mg/kgq48 – 96h Ciprofloxacin600mgq12hor400mgq8h400mgq12h400mgq12h400mgq24h Levofloxacin500mgq12h750mgq24h500mgq24h500mgq48h Vancomycin30mg/kgq24hCI500mgq6h500mgq12h500mgq24 – 72h TeicoplaninLD12mg/kgq12hfor3to 4doses;MD6mg/kgq12h LD12mg/kgq12hfor3to 4doses;MD4to6mg/kgq12h LD12mg/kgq12hfor3to 4doses;MD2to4mg/kgq12h LD12mg/kgq12hfor3to 4doses;MD2to4mg/kgq24h TigecyclineLD100mg;MD50mgq12hLD100mg;MD50mgq12hLD100mg;MD50mgq12hLD100mg;MD50mgq12h Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page4of16 http://www.wjes.org/content/9/1/22

PAGE 5

Regardingtheadministrationofantibiotics,treatment efficacyagainstacertainmicroorganismcaninvolvethe specificdrugconcentrationand/orthetimewhenthe drugisintroducedtothebindingsite[36]. Concentration-dependentantibiotics,suchasaminoglycosidesandquinolones,aremoreeffectiveathigher concentrations.Theythereforefeatureaconcentrationdependentpost-antibioticeffect,andbactericidalaction continuesforaperiodoftimeaftertheantibioticlevel fallsbelowtheminimuminhibitoryconcentration (MIC)[36]. Concentration-dependentagentsadministeredinhigh dosage,short-course,once-a-daytreatmentregimens maypromotemorerapidandefficientbactericidalaction andpreventthedevelopmentofresistantstrains. Thereisgoodevidenceforextendeddurationofaminoglycosidedosingincriticallyillpatients.Intermsoftoxicity,aminoglycosidesnephrotoxicityiscausedbyadirect effectontherenalcortexandtheuptakeintotherenal cortexcanbesaturated.Thusadosingstrategyofextendeddurationreducestherenalcortexexposuretoaminoglycosidesandreducestheriskofnephrotoxicity[37]. Time-dependentantibiotics,suchas -lactamsand glycopeptides,demonstrateoptimalbactericidalactivity whendrugconcentrationsaremaintainedabovethe MIC.Unlikeconcentration-dependentagents,theyhave anegligiblepost-antibioticeffect. Theefficacyoftime-dependentantibacterialagentsin severelyillpatientsisbasedontheconstantmaintenanceofsupra-inhibitorydrugconcentrations;assuch, cliniciansshouldconsidermultipledosesperday[38]. Incriticallyillpatients,continuousinfusionof -lactam antibioticsmayfacilitatefasterandmoreconsistenttherapeuticlevelsascomparedtointermittentbolusdosing.Althoughrandomizedclinicaltrialsareneededtoconfirm thesefindings,continuousinfusionof -lactamantibiotics hasproventobeausefultime-dependentapproachfor treatingcriticallyillpatients[39]. Theempiricallydesignedantimicrobialregimenis basedontheunderlyingseverityofinfection,thepathogenspresumedtobeinvolved,andtheriskfactorsindicativeofmajorresistancepatterns. Intra-abdominalinfectionsincriticallyillpatientscan betreatedwitheithersingleormultipleantimicrobial regimensdependingontherangerequirementsofantimicrobialcoverage[40]. Piperacillin/tazobactamisabeta-lactam/beta-lactamase inhibitorcombinationwithinvitroactivitytowardsgrampositive(includingEnterococci),gram-negativeandanaerobicorganisms[41]. Piperacillin/tazobactamretainsinvitroactivityagainst broad-spectrumbeta-lactamase-producing,manyextended-spectrumbeta-lactamase-producingEnterobacteriaceaeandmany Pseudomonas isolates[42].Itisstilla goodantimicrobialagentincriticallyillpatientswith community-acquiredintra-abdominalinfections. Carbapenemshaveaspectrumofantimicrobialactivity thatincludesGram-positive(exceptresistantgrampositivecocci)andGram-negativeaerobicandanaerobic pathogens. Group2carbapenemsincludeimipenem/cilastatin, meropenemanddoripenem,sharingactivityagainstnonfermentativegram-negativebacilliandbeingparticularly suitableforsevereintra-abdominalinfections[43]. Doripenemisanew1--methylcarbapenemwhich, similarlytoimipenemandmeropenem,hasabroadspectrumactivityagainstGram-positive,Gram-negative, andanaerobicbacteria[44].Doripenemseemsmore effective,invitro,thanmeropenemandimipenemagainst Pseudomonasaeruginosa[44]. Inthelastfewyearscarbapenemoverusehasbeen associatedwithincreasingratesofresistanceamong enterobacteriacea[45],particularly Klebsiellapneumonia. Fromanepidemiologicalpointofview,itisnecessarytocontrolthespreadofcarbapenemaseproducing gramnegativebacteriabyoptimizationofcarbepenems use.Theuseofcarbapenemsincriticallyillpatientsis acceptableandwellindicated.Tigecyclinerepresentsa validoptionforcomplicatedintra-abdominalinfections duetoitsfavorableinvitroactivityagainstenterococci, ESBL-producingstrainsof E.coli and Klebsiella and anaerobicorganisms.Tigecyclinehasshowedalsoconsiderableantimicrobialactivityagainst Acinetobacter spp [46,47].Itdoesnothaveinvitroactivitytowards Pseudomonasaeruginosa and Proteusmirabilis. Givenitsinvitroactivityagainstmultidrugresistant (MDR)bacteria,tigecyclinerepresentsaninteresting treatmentoptionforintra-abdominalinfectionsatrisk forMDR[48]. Recently,ananalysisofclinicaltrialsforbothapproved andunapprovedindicationsfortigecycline(includingone trialoncomplicatedintra-abdominalinfections),showed anincreasedriskofdeathamongpatientsreceivingtigecycline.ThisobservationledtoaFDArecommendation againsttheuseoftigecyclineinsevereinfections[49]. Becauseofitstissuepenetrationinperitonealandsoft tissues[50],tigecyclineisaveryusefuldrugusedin peritonealinfections.Inpatientswithseveresepsisor septicshockofabdominalorigin,inwhichtheinflammatoryprocessextendstothecirculatorysystem, tigecyclineshouldalwaysbeassociatedwithanotherantimicrobial. Althoughtheepidemiologicalroleofcandidaspecies inintra-abdominalinfectionshasnotyetbeenconclusivelydefinedbythemedicalcommunity,theclinical roleofcandidaisneverthelesssignificantgiventhat invasivecandidiasisisgenerallyassociatedwithpoor clinicalprognosis.However,thepresenceof Candida inSartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page5of16 http://www.wjes.org/content/9/1/22

PAGE 6

patientswithnosignsofinfectionisconsideredacontaminantandmaynotrequiretreatment. Fluconazolehasbeenwidelyusedforthetreatmentof candidiasissinceitsapprovalbytheFDAin1990. Theazolesactprimarilybyinhibitingthecytochrome P450-dependentenzymelanosterol14-alpha-demethylase, necessaryfortheconversionoflanosteroltoergosterolin thecellularmembraneoffungi[51]. Most C.albicans isolatedfrominvasivecandidiasis infections,remainfullysusceptibletofluconazole,which hasbeenthetreatmentofchoicefortheseinfectionsin mostsettingsincludingintra-abdominalinfections[52]. However,epidemiologicaldatademonstratethatthefrequencyof Candida infectionsisrising,withanincrease intheproportionofinfectionscausedbynon-albicans Candida speciesthatareintrinsicallyresistantorvariablysusceptibletofluconazole[52]. Severalrandomizedclinicaltrialshavedemonstrated theefficacyoftheechinocandinsinthetreatmentof candidaemiaandinvasivecandidiasis[53]. Theechinocandins:anidulafungin,caspofungin,and micafunginhaveabroadandsimilarspectrumofinvitro andinvivoactivityagainstmostCandidaspp.[54]. Echinocandinshaveseveralpotentialadvantagesover fluconazoleforthetreatmentofinvasivecandidiasis.They haveabroaderspectrumofactivity(encompassingfluconazole-resistant C.glabrata and C.krusei )andpotentfungicidalactivityagainstmostCandidaspecies[55]. Inthespecificsettingofintra-abdominalinfections, echinocandinsaregenerallyrecommendedasafirstline empirictherapyforcriticalillpatients,whilefluconazole istypicallyrecommendedforlessseverecases[21].HaemodynamicsupportOneofthemostlikelyexplanationsforthehighmorbidity andmortalityratesassociatedwithseveresepsisisthe developmentofcardiovascularinsufficiency,whichcan leadtoglobaltissuehypoxia. Inseveresepsis,theearlyhaemodynamicprofileischaracterizedbyhypovolaemia,vaso-regulatorydysfunction, andmyocardialdepression.Increasedcapillaryleakage andvenouscapacitanceultimatelyresultindecreasedvenousreturntotheheart.Additionally,cytokinesreleased duringthepatient ’ simmuneresponsemaytriggerfurther myocardialdepression. Thesehaemodynamicalterationsassociatedwiththe earlystagesofsepsisareoftenaccompaniedbyanincrease insystemicoxygendemandandimpairedoxygendelivery, therebyinducingglobaltissuehypoxia.Globaltissuehypoxiamayoverstimulateendothelialcellactivity,whichcan subsequentlyleadtothesystemicinflammatorycascade characteristicofsepsis[56,57]. Earlytreatmentwithaggressivehaemodynamicsupportcanlimitthedamageofsepsis-inducedtissue hypoxiaandpreventtheoverstimulationofendothelialactivity. Riversetal.[58]demonstratedthatearlygoal-directed therapy(EGDT),initiatedintheemergencydepartment, reducesthein-hospitalmortalityratesofpatientsinsepticshock. Ithasbeenestablishedthatthegeneralprognosticvalue ofalactateof4mM/Lonhospitaladmissionisimportant; multiplestudieshaveconfirmedtheriskstratificationof thislactatelevelforillnessseverityandmortalityinboth thepre-hospitalandin-hospitalsetting[59-63].Lactate clearancehasalsobeenassociatedwithdecreasedmortalityinpatientswithseveresepsisandsepticshock[64]. However,20to50%ofsepticshockpatientsdonothave elevatedlactatelevelsatpresentationorduringtheirclinicalcourse,yetstilldeveloporganfailure[65-67].FluidresuscitationFluidresuscitationshouldbeinitiatedasearlyaspossibleinthecourseoftreatmentforseveresepsisregardlessofapatient ’ slactatelevel. Fluidresuscitationisamajorcomponentofcardiovascularsupportinearlysepsis.Althoughtheneedforfluid resuscitationinsepsisiswellestablished,thegoalsand componentsofthistreatmentarestillamatterofdebate alsoinpatientswithperitonitis. Theabsenceofclearbenefitsfollowingtheadministrationofcolloidsolutionscomparedtocrystalloid[68], supportsahigh-graderecommendationfortheuseof crystalloidsolutionsintheinitialresuscitationofpatientswithseveresepsisandsepticshock[11]. Intravascularvolumeisthefirstparametertobeassessed duringhemodynamicoptimization. Inpatientswithgeneralizedperitonitis,fluidresuscitationshouldbekeptundercontroltoavoidfluidsoverload, whichmayaggravategutoedemaandleadtoincreased intra-abdominalpressure.Increasingintra-abdominal pressurecausesprogressivehypoperfusionofsplanchnic circulation.Pathophysiologicaleffectsincludegutoedema leadingtobacterialtranslocationandreleaseofcytokines, thereforeaggravatingthesepsiscascade[69]. Severalstudieshavealreadyshownthatapositivefluid balanceincriticalillnessmaybestronglyassociatedwitha higherseverityoforgandysfunctionandwithworseoutcomes[70]. Pathophysiologicalmechanismsassociatedwiththeinflammatoryresponseleadtocapillaryleakage.Although crystalloidsareisotonic,asignificantamountofthe volumegivenmaymigrateintotheextra-vascularspace duetoincreasedcapillarypermeabilityandchangesin oncoticpressure. Inpatientwithseveregeneralizedperitonitisexcessive infusionoffluidsmaybecomeacounterproductive strategy.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page6of16 http://www.wjes.org/content/9/1/22

PAGE 7

Thefrequencywithwhichintra-abdominalhypertensiondevelopsinabdominalsepsismayhaveotherimportantclinicalconsequencesinadditiontoitsimpact onsepsisresuscitationendpoints.Currentsurviving sepsisguidelinesemphasizetheimportanceoftraditional meanarterialpressure(MAP)>65mmHg,centralvenouspressure(CVP)of8 – 12mmHgincombinationwith acentralvenousoxygensaturation(ScvO2)>70%and Urineoutput>0.5mL/kg/hr[11].However,inpatients withseveresepsisorsepticshockofabdominalorigin, highintra-abdominalpressuremayprofoundlyinfluence commonlyusedsepticshockresuscitationendpoints suchasCVP(falselyelevated)andurineoutput(markedlydecreased). Repeatedintravesicalmeasurementsofintra-abdominal pressureshouldbefrequentlyperformedinpatientswith severesepsisorsepticshockofabdominalorigin,toidentifypatientsatriskforintra-abdominalhypertension. Monitoringthefluidstatusofcriticallyillpatientsatrisk forintra-abdominalhypertensioniscrucial.Inrecent decadeswehavewitnessedrapidadvancesinfluidmonitoringtechniques.Pulmonaryarterycatheters(PACs)have beenwidelyusedformorethanthreedecades,buttheir usefulnessinimprovingpatientoutcomesseemsdisappointing.TrialshaveconsistentlyshownthatPACsdono improvepatientoutcomesandmaysignificantlyincrease medicalcosts[71].WiththedeclininguseofPACs, therehasbeenanincreasingnumberofalternatives forhemodynamicmonitoring. Echocardiographyisausefulnoninvasivetoolwhich candirectlyvisualizetheheartandassesscardiacfunction.Itsusewaslonglimitedbytheabsenceofaccurate indicestodiagnosehypovolemiaandpredicttheeffect ofvolumeexpansion.Inthelastyearsechocardiography hasbeenusedtodevelopnewparametersoffluidresponsiveness,takingadvantageofitsabilitytomonitor cardiacfunction.Echocardiographyhasbeenshownto predictfluidresponsivenessaccuratelyandisnowa completeandnoninvasivetoolabletoaccuratelydeterminehemodynamicstatusincirculatoryfailure[72,73]. Itisstronglyoperator-dependent,anditdoesnotallow continuousmonitoring. ThePiCCOsystem(PulseindexContourContinuous CardiacOutput,PulsionMedicalSystems,Germany)is anotherinterestingalternative.Itincorporatesatranspulmonarythermodilutiontechnique(TPTD)andcontinuouspulsecontouranalysis.Itisminimallyinvasiveand doesnotrequireintracardiaccatheterization.Itcangive beat-by-beatmonitoringofcardiacoutput,andcan provideaccurateinformationonvolumestatus[74].VasopressoragentsVasopressoragentsshouldbeadministeredearlyin patientswithseveresepsisorsepticshockofabdominal origintorestoreorganperfusion.Theirearlyusemay preventexcessivefluidresuscitation. Vasopressordrugsmaintainadequatebloodpressure andpreserveperfusionpressurethusoptimizingblood flowinvariousorgans.Norepinephrineisnowthefirstlinevasopressoragentusedtocorrecthypotensionin theeventofsepticshock[11].Norepinephrineismore efficaciousthandopamineandmaybemoreeffectivefor reversinghypotensioninpatientswithsepticshock. In1993,Martinetal.showedinaprospective,doubleblind,randomizedtrialthatnorepinephrinewasmore effectiveandreliablethandopaminetoreversetheabnormalitiesofhyperdynamicsepticshock[75].TheSurviving SepsisCampaignguidelinesfavournorepinephrine[11] andtherehavebeenstudiessincethe2008updateto bolsterthispreference.DeBackeretal.investigatedthis questioninameta-analysis,focusingonlyonthose patientswithsepticshockandagainshowedthat dopaminewasassociatedwithgreatermortalitythan norepinephrine[76]. Itiswellknownthatdopaminemaycausemoretachycardiaandmaybemorearrhythmogenicthannorepinephrine[77],andasanalternativevasopressoragentto norepinephrine,itshouldbeusedonlyinpatientswith lowriskoftachyarrhythmiasandabsoluteorrelative bradycardia. Epinephrineisapotent -adrenergicand -adrenergic agentthatincreasesmeanarterialpressurebyincreasing both,cardiacindexandperipheralvasculartone.There areconcernsregardingtheuseofepinephrineinseptic patientsduetoitspotentialtodecreaseregionalblood flow,particularlyinthesplanchniccirculation,andelevationsinserumlactate.However,notrialshaveshown thatepinephrineresultsinworseoutcomes,soitmaybe usedasanalternativetonorepinephrine[78,79]. Vasopressinisapeptidehormonesynthesizedinthe hypothalamusandsubsequentlytransportedtothepituitaryglandwhereitisstored.Itisreleasedinresponse todecreasedbloodvolume,decreasedintravascularvolume,andincreasedplasmaosmolality.VasopressinconstrictsvascularsmoothmusclebydirectlyactivatingV1 receptorsandsimultaneouslyincreasingthevasculature ’ s responsivenesstocatecholamines[80]. Vasopressin(upto0.03U/min)canbeaddedtonorepinephrinewiththeintentofraisingMAPtotargetor decreasingthenorepinephrinedose[11].InotropicagentsDobutamineisfrequentlyusedtotreatsepticshock patientsasaninotropicagentincreasingcardiacoutput, strokeindex,andoxygendelivery(Do2).However,the tendencyofdobutaminetoincreaseDo2tosupranormalvaluesincriticallyillpatientshasraisedserious questionsregardingitssafetyinthetreatmentofsepticSartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page7of16 http://www.wjes.org/content/9/1/22

PAGE 8

shock.TheSurvivingSepsisCampaignGuidelinesrecommend[11]thatadobutamineinfusionshouldbeadministeredintheeventofmyocardialdysfunctionasindicated byelevatedcardiacfillingpressuresandlowcardiacoutputorongoingsignsofhypoperfusion,despiteachieving adequateintravascularvolumeandadequateMAP.AcutekidneyinjuryinsurgicalsepsisInpatientswithsurgicalsepsis,particularattention shouldalwaysbepaidtoacutekidneyinjury(AKI).A prospectiveobservationalinstitutionalstudyrecently published,hasshownthatAKIfrequentlycomplicates surgicalsepsis,andservesasapowerfulpredictorof hospitalmortalityinseveresepsisandsepticshock.Duringthe36-monthstudyperiodendingonDecember 2010,246patientstreatedforsurgicalsepsiswereevaluatedinthestudy.AKIoccurredin67%ofallpatients, and59%,60%,and88%ofpatientshadsepsis,surgical sepsis,andsepticshock,respectively. PatientswithAKIhadfewerventilator-freeandintensivecareunitfreedaysandadecreasedlikelihoodof dischargetohome.Morbidityandmortalityincreased withseverityofAKI,andAKIofanyseveritywasfound tobeastrongpredictorofhospitalmortality(oddsratio, 10.59;95%confidenceinterval,1.28Y87.35;p=0.03)in surgicalsepsis[81].SourcecontrolInitialoperationThetimingandadequacyofsourcecontrolareofoutmostimportanceinthemanagementofintra-abdominal sepsis,aslateand/orincompleteproceduresmayhave severelyadverseconsequencesonoutcome. Sourcecontrolencompassesallmeasuresundertaken toeliminatethesourceofinfection,reducethebacterial inoculumandcorrectorcontrolanatomicderangements torestorenormalphysiologicfunction[82,83]. Thisgenerallyinvolvesdrainageofabscessesorinfected fluidcollections,debridementofnecroticorinfectedtissuesanddefinitivecontrolofthesourceofcontamination. Itiswellknownthatinadequatesourcecontrolatthe timeoftheinitialoperationhasbeenassociatedwithincreasedmortalityinpatientswithsevereintra-abdominal infections[84]. Earlycontrolofthesepticsourcecanbeachieved usingbothoperativeandnon-operativetechniques. Anoperativeinterventionremainsthemostviable therapeuticstrategyformanagingintra-abdominalsepsis incriticalillpatients. Theinitialaimofthesurgicaltreatmentofperitonitis istheeliminationofbacterialcontaminationandinflammatorysubstancesandpreventionorreduction,ifpossible,offibrinformation. Generally,thesurgicalsourcecontrolemployeddependsontheanatomicalsourceofinfection,thedegree ofperitonealinflammationandgeneralizedsepticresponse, andthepatient ’ spre-morbidcondition. Surgicalsourcecontrolentailsresectionorsutureofa diseasedorperforatedviscus(e.g.diverticularperforation, gastroduodenalperforation),removaloftheinfectedorgan (e.g.appendix,gallbladder),debridementofnecrotic tissue,resectionofischemicbowelandrepair/resection oftraumaticperforationswithprimaryanastomosisor exteriorizationofthebowel. Laparotomiesareusuallyperformedusingamidline incision. Theprimaryobjectivesofsurgicalinterventioninclude a)determiningthecauseofperitonitis,b)drainingfluid collections,c)controllingtheoriginoftheabdominal sepsis. Specialattentionshouldbegiventoareaswhere abscessesmayformsuchasthepelvis,thepara-colic gutters,andthesubphrenicspaces.Theseareasshould becarefullyexposedanddebrided,avoidingbleedingby excessivepeelingofthefibrin,anddrained. Incaseofsuspectedgastro-intestinalperforation,the wholeextentoftheGItract,startingfromthegastroesophgealjunctiontothelowerrectumshouldbethoroughlyandcarefullyexamined.Ifnoperforationisfound, thegastrocolicomentumshouldalwaysbeopenedtoexposethelessersactoallowvisualizationoftheposterior wallofstomachforanyhiddenperforationaswellascarefulexaminationofthebodyandtailofpancreas. Specialattentionshouldbepaidwhiledrainingand debridingtheleftsubphrenicspacesincethereishigh riskofsplenicinjuryduringsurgicalmanipulationdue tofibrinousadhesionswiththespleniccapsule.Splenic bleedingmaybedifficulttocontrolduetoadhesionsand mightwarrantsplenectomywhichaddstothemorbidity andpotentialmortalityinanalreadycompromised patient. Intra-abdominallavageisamatterofongoingcontroversy.Someauthorshavefavouredperitoneallavage becauseithelpsinremovalaswellasindilutionofperitonealcontaminationbyirrigationwithgreatvolumesof saline[85].However,itsapplicationwithorwithoutantibioticsinabdominalsepsisislargelyunsubstantiatedin theliterature[86]. Inrecentyears,laparoscopyhasbeengainingwider acceptanceinthediagnosisandtreatmentofintraabdominalinfections. Laparoscopicapproachinthetreatmentofperitonitis isfeasibleandeffectivewithoutanyspecificcomplicationsinexperiencedhands.Laparoscopyhastheadvantagetoallow,atthesametime,anadequatediagnosisand appropriatetreatmentwiththelessinvasiveabdominal approach[87].However,inunstablepatientslaparoscopySartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page8of16 http://www.wjes.org/content/9/1/22

PAGE 9

isgenerallyavoidedbecauseincreasedintra-abdominal pressureduetopneumoperitoneumseemstohaveanegativeeffectincriticalillpatientsleadingtoacid – basebalancedisturbances,aswellaschangesincardiovascular andpulmonaryphysiology[88].RelaparotomystrategyIncertaincircumstances,infectionnotcompletelycontrolledmaytriggeranexcessiveimmuneresponseand sepsismayprogressivelyevolveintoseveresepsis,septic shock,andorganfailure[89]. Suchpatientswouldbenefitfromimmediateandaggressivesurgicaltreatmentwithsubsequentre-laparotomy strategies,tocurbthespreadoforgandysfunctionscaused byongoingsepsis. Unfortunately,earlyassessmentoftheseverityofperitonitisisdifficultinemergencysurgicalpatientsand noneoftheexistingandwidelyused ‘ severity-of-disease ’ scores,specificallydevelopedforcriticallyillpatients, wereclinicallyusefulintheidentificationofpatients withongoinginfectionneedingare-laparotomy[90]. Surgicalstrategiesfollowinganinitialemergencylaparotomyincludesubsequent “ re-laparotomyondemand ” (whenrequiredbythepatient ’ sclinicalcondition)as wellasplannedre-laparotomyinthe36-48-hourpostoperativeperiod. On-demandlaparotomyshouldbeperformedonly whenabsolutelynecessaryandonlyforthosepatients whowouldclearlybenefitfromadditionalsurgery. Severalstudieshaveevaluatedclinicalvariablesthatmay beassociatedwiththeneedforon-demandre-laparotomy intheimmediatepost-operativeperiod[91-97]. VanRuleretal.[92]in2008reportedtheresultsofa questionnaireaskingsurgeonstoranktheimportanceof 21clinicalvariablesontheirdecisiontore-operateinpatientswithsecondaryperitonitis.Theyfoundthatdiffuse extentoftheabdominalcontamination,localizationofthe infectiousfocus(uppergastrointestinaltractincluding smallbowel),andboth,extremelylowandhighleukocyte counts,independentlypredictedare-laparotomy.These variableshadonlymoderatepredictiveaccuracy.Theresultsofthequestionnairedemonstratedthattherewasno consensusamongsurgeonsaboutwhichvariablesareimportantinthedecision-makingprocessforre-laparotomy. Thefinaldecisiontoperformare-operationonapatient intheon-demandsettingisgenerallybasedonthepatients generalizedsepticresponseandonthelackofclinical improvement. Performingacase – controlstudy,KopernaandSchulz [91]retrospectivelyreviewed523consecutivepatients withsecondaryperitonitis.Theyfocusedtheirattention on105patients,inwhomstandardsurgicaltreatmentof secondaryperitonitisfailedandwhohadtoundergorelaparotomyforpersistingabdominalsepsis(studygroup). Theauthorsshowedthatpatientsre-operatedonafter 48hourshadasignificantlyhighermortalityratethan thoseoperatedonearlier(76.5%versus28%;p<.001). Plannedrelaparotomies,ontheotherhand,areperformedevery36 – 48hoursforpurposesofinspection, drainage,andperitoneallavageoftheabdominalcavity. Theconceptofaplannedrelaparotomyforsevere peritonitishasbeendebatedforoverthirtyyears.Reoperationsareperformedevery48hoursforreassessing theperitonealinflammaryprocessuntiltheabdomenis freeofongoingperitonitis;thentheabdomenisclosed. Theadvantagesoftheplannedre-laparotomyapproachare optimizationofresourceutilizationandreductionofthe potentialriskforgastrointestinalfistulasanddelayed hernias. Theresultsofaclinicaltrialpublishedin2007investigatingthedifferencesbetweenon-demandandplanned re-laparotomystrategiesinpatientswithsevereperitonitisfoundfewadvantagesfortheplannedre-laparotomy strategy;however,thestudymentionedthatthislatergroup exhibitedareducedneedforadditionalre-laparotomies, decreasedpatientdependencyonsubsequenthealthcare services,anddecreasedoverallmedicalcosts[98].OpenabdomenAnopenabdomen(OA)procedureisthebestwayof implementingre-laparotomies.TheroleoftheOAin themanagementofsevereperitonitishasbeenacontroversialissue. In2007,arandomisedstudycomparedopenandclosed abdomensforthe “ ondemandre-laparotomy ” groupin thetreatmentofsevereperitonitis.Thestudywasprematurelyterminatedfollowingthetreatmentof40subjects duetoasignificantlyhighermortalityrateintheopenabdomengroupcomparedtothetemporarilyclosedabdomengroup(55%vs.30%).OAprocedureswereperformed usingonlynon-absorbablepolypropylenemesh[99]. Althoughguidelinessuggestnottoroutinelyutilize theopenabdomenapproachforpatientswithsevere intra-peritonealcontaminationundergoingemergency laparotomyforintra-abdominalsepsis[100],OAhas nowbeenacceptedasastrategyintreatingintraabdominalsepsis[101]. AnOAapproachinseveresecondaryperitonitismaybe requiredforthreedifferentreasons,oftenusedincombination:inadequatesourcecontrol,severelyderangedphysiology(theoperationispurposelyabbreviatedduetothe severephysiologicalderangementandsuboptimallocal conditionsforhealing,andrestorationofintestinalcontinuityisdeferredtothesecondoperation,i.e.thedeferred anastomosisapproach)[102],andpreventionofabdominalcompartmentsyndrome[103-105]. TherationaleoftheOAstrategyinpatientswith severeabdominalsepsisreferstothecytokinereleaseSartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page9of16 http://www.wjes.org/content/9/1/22

PAGE 10

thatiscompartmentalizedintheperitonealcavity. Inabilitytocontrolorinterruptthelocalinflammatory responseisassociatedwithhighermortalityratesin thesepatients.Theattenuationofthelocalinflammatory responsemaybebestachievedwithmechanicalcontrol byreducingtheloadofcytokinesandotherinflammatorysubstances[106]andbypreventingtheirproduction,thusremovingthesourceitself.Sometimesmore laparotomiesarerequiredtocompletesourcecontrol andOAallowsthesurgeontoperformsubsequent plannedlaparotomiesmoreefficiently. Aninterestingnon-comparativedescriptivecaseseries [106]studiedtheinflammatoryresponseinperitoneal exudateandplasmaofpatientsundergoingplannedrelaparotomyforseveresecondaryperitonitis.Insepticpatientsundergoingre-laparotomyforsevereperitonitis, endotoxin,tumournecrosisfactoralpha,interleukin-1 andinterleukin-6levels,werehigherintheperitoneal cavitytheninplasma.Whenpatientsunderwentrelaparotomy,thelevelofthosecytokineswassignificantly decreasedinsurvivors. OAmanagementhasbeendescribedinpatientswith intra-abdominalsepsiswhenasinglelaparotomyfailed tocontrollocalinflammatoryresponse,ortheriskof organdysfunctionincreasedaftereffectivedrainageand debridement[107-109]. Intheeventofmassivefluidresuscitation,bowel oedemaandtheforcedclosureofanon-compliant abdominalwallmaycauseintra-abdominalhypertension (IAH).UncontrolledIAHexceeding25mmHgmay causeabdominalcompartmentsyndrome(ACS),which isapotentiallylethalcomplicationcharacterizedby adverseeffectsonpulmonary,cardiovascular,renal, splanchnic,andcentralnervoussystemphysiology[109]. ThecombinationofIAHandthephysiologicaleffects ofsepsis,resultinhighmorbidityandmortalityrates.At presenttherearenodefinitecriteriatoguidethesurgeonindecidingwhethertousetheOAstrategy[110]. TheOAstrategyallowssurgeonstoextendtheconcept ofdamagecontrolsurgerytoabdominalseveresepsis. Thetermdamagecontrolsurgery(DCS)fortrauma patientswasintroducedin1993.Itwasdefinedasinitial controlofhaemorrhageandcontamination,allowingfor resuscitationtonormalphysiologyintheintensivecare unitandsubsequentdefinitivere-exploration[111,112]. Theadaptationofdamagecontrolsurgeryfortrauma tootherareasgenerallyisusefulinthosepatientswho areatrisktodevelopasimilarlossofphysiologicreserve withintolerancetotheshockedphysiologicalstate[113]. Similarlytothetraumapatientwiththelethaltriadof acidosis,hypothermiaandcoagulopathy,manypatients withseveresepsisorsepticshockmaypresentina similarfashion.Forthosepatients,DCScantrulybelife saving.Patientsprogressingfromsepsisthroughsevere sepsiswithorgandysfunctionintosepticshock,can presentwithvasodilation,hypotension,andmyocardial depression,combinedwithcoagulopathy.Thesepatients areprofoundlyhaemodynamicallyunstableandare clearlynotoptimalcandidatesforcomplexoperativeinterventions[114]. Abdominalclosureshouldbetemporary,andthe patientisrapidlytakentotheICUforphysiologic optimization.Thisincludesoptimizationofvolume resuscitationandmechanical ventilation,correctionof coagulopathyandhypothermia,andmonitoringfor eventualACSdevelopement.Overthefollowing24to 48hours,whenabnormalphysiologyiscorrectedthe patientcanbesafelytakenbacktotheoperatingroom forre-operation. AnadditionaladvantageofDCSinabdominalsepsisis thepossibilitytodelaythebowelanastomosis[115]. Thesurgicalstrategyforthemanagementofpatients withcompromisedbowelinsecondaryperitonitishas beenusuallytheresectionoftheperforatedviscus followedbyprimaryanastomosisoradiversion.Inpatientswithseveresecondaryperitonitisandsignificant hemodynamicinstabilityandcompromisedtissueperfusion,theuseofprimaryanastomosisislimitedbecause ofthehighriskofsuture/anastomoticfailure,leakage, andincreasedsurgicalmortality.Inthesepatients,itis advisabletocontrolthesourceofperitonealcontaminationandtoperformanintestinalostomydelaying bowelanastomosis. InaretrospectivestudyfromColombia,112patients withsecondaryperitonitisrequiringbowelresectionand managedwithstagedlaparotomywereanalyzed[116]. Deferredprimaryanastomosiswasusedin34patients wherethebowelendswereclosedatfirstoperationand definitiveanastomoseswerereconstructedatthesubsequentoperationfollowingphysiologicalstabilizationin theICUandrepeatedperitonealwashesuntiltheseptic sourcewascontrolled.Incontrast,78patientsunderwentsmallbowelorcolonicdiversionfollowedbysimilarICUstabilizationandperitonealwashes.Inboth groups,theabdomenswereleftopenattheinitialoperationandaVelcrosystemorvacuumpackwasusedfor temporaryabdominalclosure.Themeannumberof laparotomieswasfourinbothgroups.Thereweremore patientswithcolonresectionsinthediversiongroup (80%vs.47%).Therewasnosignificantdifferencein hospitalmortality(12%fordeferredanastomosisvs.17% fordiversion),frequencyofanastomoticleaksorfistulas (9%vs.5%),orARDS(18%vs.31%).Theauthorsconcludedthatincriticallyillpatientswithseveresecondary peritonitismanagedwithstagedlaparotomies,deferred primaryanastomosiscanbeperformedsafelyaslongas adequatecontrolofthesepticfociandrestorationof derangedphysiologyisachievedpriortoreconstruction.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page10of16 http://www.wjes.org/content/9/1/22

PAGE 11

Inanon-randomizedstudyof27consecutivepatients withperforateddiverticulitis(HincheyIII/IV),thepatients weremanagedeitherwithsigmoidresectionandprimary anastomosis,orlimitedsigmoidresectionorsuture,open abdomenandprimaryanastomosisorcolostomyatsecondoperation24 – 48hourslater,orHartmannprocedure; sigmoidresectionandendcolostomy[117].All6patients withprimaryanastomosissurvivedwithoutcomplications, buttherewasanobviousselectionbias.Ofthe6patients undergoingHartmann ’ sprocedure,onediedofsepsisand 5weredischargedwithstoma.Intheinterestinggroupof 15patientswithdeferredanastomosisorstomaandopen abdomen,9patientshadintestinalcontinuityrestored duringthesecondlookoperationwithonefatalanastomoticleakage. Inaprospectivestudyof51patientswithperforated diverticulitis(HincheyIII/IV)wereinitiallymanaged withlimitedresection,lavageandTACwithvacuumassistedclosurefollowedbysecond,reconstructiveoperation24 – 48hourslater[118].Bowelcontinuitywas restoredin38patients,in4protectedbyaloopileostomy.Fiveanastomoticleaks(13%)wereencountered requiringloopileostomy(2patients)orHartmann ’ s procedure(3patients).Postoperativeabscesseswere seenin4patients,abdominalwalldehiscenceinoneand re-laparotomyfordrain-relatedsmallbowelperforation inone.Theoverallmortalityratewas10%and35/46 (76%)ofthesurvivingpatientsleftthehospitalwithreconstructedcoloncontinuity.Fascialclosurewasachieved inallpatients. Followingstabilizationofthepatient,thegoalisthe earlyanddefinitiveclosureoftheabdomen,inorderto reducethecomplicationsassociatedwithanopenabdomen[119]. Areviewoftheliteraturesuggestsabimodaldistributionofprimaryclosurerates,withearlyclosuredependent onpostoperativeintensivecaremanagementwhilst delayedclosureismoreaffectedbythechoiceofthetemporaryabdominalclosuretechnique[120]. Primaryfascialclosurecanbeachievedinmany caseswithinfewdaysfromtheinitialoperation.It wouldnotbesuccessfulifearlysurgicalsourcecontrol failed[121,122]. Sequentialfascialclosurecouldimmediatelybestarted onceabdominalsepsisiswellcontrolled[123].Inthese cases,surgeonsshouldperformaprogressiveclosure, wheretheabdomenisincrementallyclosedeachtime thepatientundergoesareoperation. Within10to14daysthefasciaretractslaterallyand becomesadherenttotheoverlyingfat;thismakesprimaryclosureimpossible.Therefore,itisimportantto preventtheretractionofthemyo-fascialunit. Severalmaterialscanbeusedtoachievetemporary closureoftheabdomen:gauze;mesh;impermeableselfadhesivemembranedressings,zippersandnegativepressuretherapy(NPT)techniques. Theidealtemporaryabdominalclosuremethodshould beabletoprotecttheabdominalcontents,toprevent evisceration,toallowremovalofinfectedortoxicfluid fromtheperitonealcavity,topreventtheformationof fistulas,toavoiddamagetothefascia,topreservethe abdominalwalldomain,tomakere-operationeasy,safe andfacilitatedefinitiveclosure[110]. ThesurgicaloptionsformanagementoftheOAare nowmorediverseandsophisticated,butthereisalack ofprospectiverandomizedcontrolledtrialsdemonstratingthesuperiorityofanyparticularmethod. Atpresent,negativepressuretherapy(NPT)techniqueshavebecomethemostextensivelyusedmethods fortemporaryabdominalwallclosure.NPTactively drainstoxinorbacteria-richintraperitonealfluidand hasresultedinahighrateoffascialandabdominalwall closure[110]. Asystematicreviewconductedin2012[124]found only11comparativestudies,including2randomized controlledtrials(RCTs)and9cohortstudies,examining theefficacyandsafetyofnegativepressureperitoneal therapy versus alternatetemporalabdominalclosure methodsamongcriticallyillorinjuredadults. However,allstudieswereassociatedwithatleastamoderateriskofbiasandsignificantclinicalheterogeneity,the authorsconcludedthattherewasinsufficientevidenceto supportthepreferentialuseofnegativepressureperitonealtherapyafterdamagecontrollaparotomy. AnimaldatasuggestthatOAtechniquesemploying constantnegativepressuretotheperitonealcavitymay removeinflammatoryascites,reducethesystemicinflammatoryresponse,andimproveorganinjuryandpotentiallyoutcomes[125]. Thismethodisstillassociatedwithhighmorbidity andhighincidenceofventralherniaformationinsurvivingpatientscausedbydifficultiesindefinitiveclosureof theabdominalwallafterprolongedapplicationofNPT butitcouldbeahighlypromisingmethodinthemanagementofpatientswithincreasedIAPandseveresepsis duetosevereperitonitis[126]. Asystematicreviewpublishedin2009[127]investigated whichtemporaryabdominalclosuretechniqueisassociated withthehighestdelayedprimaryfascialclosure(FC)rate. Nocomparativestudieswereidentified.51articles wereincluded.Thetechniquesdescribedwerevacuumassistedclosure(VAC;8series),vacuumpack(15series), artificialburr(4series),Mesh/sheet(16series),zipper(7 series),silo(3series),skinclosure(2series),dynamicretentionsutures(DRS),andloosepacking(1serieseach). Theseresultssuggestedthattheartificialburrandthe VACwereassociatedwiththehighestFCratesandthe lowestmortalityrates.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page11of16 http://www.wjes.org/content/9/1/22

PAGE 12

OthertechniquesusedforprogressiveFCincludea combinationofNPTwithatemporarymeshsuturedto thefascialedges.Themeshistightenedeveryfewdays, untilthefascialdefectissmallenoughsothemeshcan beremovedandthefasciaclosedprimarily. In2012,aretrospectiveanalysisevaluatingtheuseof vacuum-assistedclosureandmesh-mediatedfascialtraction(VACM)astemporaryabdominalclosurewaspublished[128].Thestudycompared50patientstreated with(VACM)and54usingnon-tractiontechniques (controlgroup).VACMresultedinahigherfascialclosure rateandlowerplannedherniaratethanmethodsthatdid notprovidefascialtraction. Occasionally,abdominalclosureisonlypartially achieved,resultinginlatedevelopmentoflarge,debilitating herniasoftheabdominalwallwhichwilleventuallyrequire complexsurgicalrepair.Inthesecases,delayedrepairor useofbiologicalmesheshasbeenproposed[129]. Anotheroption,ifdefinitivefascialclosureisnotpossible,isclosureoftheskinonlyandsubsequentmanagementoftheeventrationbyadeferredabdominalclosure withsyntheticmeshesafterhospitaldischarge[127].AdjuntivemeasuresRecombinanthumanactivatedproteinC(rhAPC),also knownasdrotrecoginalfa,wasincludedintheprevious SurvivingSepsisCampaignguidelines[130]basedonthe PROWESSstudygroup[131]andENHANCEstudy group[132]studies. BasedonthepreliminarydataofthePROWESSSHOCKstudy[133],showinga28-dayall-causemortality rateof26.4%inpatientstreatedwithrhAPCcompared with24.4%inthosegivenplacebo,theUSFoodandDrug Administration(FDA)haswithdrawndrotrecoginalfa fromthemarket[134]andnow,rhAPCshouldnotbe usedinanypatientswithsepticshock.CorticosteroidsTherecommendationsregardingtheuseofcorticosteroidshavechangedovertimeandtheclinicalbenefitsof corticosteroidsinthetreatmentofseveresepsisand septicshockremaincontroversial. Asystematicreviewofcorticosteroidsinthetreatment ofseveresepsisandsepticshockinadultpatientspublishedin2009valued17randomizedtrials(2138patients) and3quasi-randomizedtrials(n=246)ofacceptable methodologicalquality,andpooledtheresultsinasubsequentmeta-analysis[135].Theauthorsconcludedthat corticosteroidtherapyhasbeenusedinvarieddosesfor treatingsepsisandrelatedsyndromesformorethan 50years,butitsabilitytoreducemortalityrateshasnever beenconclusivelyproven.Since1998,studieshaveconsistentlyusedprolongedlow-dosecorticosteroidtherapy, andfollow-upanalysesofthissubgrouphavefoundthat suchregimenstendtoreduceshort-termmortality. In2011Annanepublishedanevidencedbasedguide [136]regardingcorticosteroidsforseveresepsis.Heconcludedthatcorticosteroidsshouldbeinitiatedonlyin patientswithsepsiswhorequire0.5 g/kgperminuteor moreofnorepinephrineandshouldbecontinuedfor5 to7daysexceptinpatientswithpoorhaemodynamic responseafter2daysofcorticosteroidsandwithacortisolincrementofmorethan250nmol/Lafterastandard adrenocorticotropinhormone(ACTH)test. TheSurvivingSepsisCampaignguidelines[11]recommendcorticosteroidsbeusedinpatientswithrefractory septicshock(poorlyresponsivetofluidsandvasopressor therapy)anddonotrecommendroutineassessmentfor relativeadrenalinsufficiency.NutritionalsupportTheeffectofnutritionalsupportincriticallyillpatients withsepsishasbeendebatedinrecentyears.Asforall criticallyillpatients,nutritionalsupport,preferablyvia theenteralroute,shouldbecommencedinpatientswith severesepsisorsepticshockonceinitialresuscitation andadequateperfusionpressureisachieved[137]. Earlyenteralnutritionhastheoreticaladvantagesin maintainingtheintegrityofthegutmucosaandonthe preventionofbacterialtranslocation. Studiesondifferentsubpopulationsofcriticallyill patients,mostlysurgicalpatients,arenotconsistentand nonewasindividuallypoweredformortality,withvery lowmortalityrates.Althoughnoconsistenteffecton mortalitywasobserved,someearlyenteralfeedingstudiesshowedbenefitonsecondaryoutcomessuchreduced lengthofmechanicalventilation,andreducedICUand hospitalstay[138-140].ConclusionsTheSurvivingSepsisCampaigninternationalguidelines formanagementofseveresepsisandsepticshockwere recentlyupdated.Theseguidelinesarethecornerstone forthemanagementofseveresepsisandsepticshock, buttheydonotfocusonthespecificsettingofintraabdominalinfections. Althoughsepsisisasystemicprocess,thepathophysiologicaleventsdifferforeveryorganandinthespecific settingofintra-abdominalinfectionsthemanagementof sepsismayvaryfromthatofsepsisofotheretiologies. Outcomesofsevereintra-abdominalinfectionsaccompaniedbyseveresepsisarerelatedtoearlydiagnosis, aggressiveandearlyoptimizationofphysiology,early surgicalmanagementwithsourcecontrolandaggressive criticalcaremanagement.Reoperationsarecommon andmaybeusefulinattenuatingtheinflammatoryresponseandoptimizingtheimmuneresponse.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page12of16 http://www.wjes.org/content/9/1/22

PAGE 13

Competinginterests Theauthorsdeclarethattheyhavenocompetinginterests. Authors ’ contributions MSwrotethemanuscript.Allauthorsreviewedandapprovedthefinal manuscript. Authordetails1DepartmentofSurgery,MacerataHospital,Macerata,Italy.2Departmentof EmergencySurgery,MaggioreParmaHospital,Parma,Italy.3TraumaSurgery Unit,MaggioreHospital,Bologna,Italy.4GeneralSurgeryDepartment,Papa GiovanniXXIIIhospital,Bergamo,Italy.5AmericanBoardofSurgery, Philadelphia,USA.6DepartmentofSurgery,DenverHealthMedicalCenter, Denver,CO,USA.7DepartmentofSurgery,UniversityofFlorida,Gainesville, Florida,USA.8DepartmentofSurgery,VirginiaCommonwealthUniversity MedicalCenter,Richmond,VA,USA.9DepartmentofSurgery,UCSanDiego HealthSystem,SanDiego,USA.10DepartmentofAbdominalSurgery, UniversityHospitalMeilahti,Helsinki,Finland.11DepartmentofGeneral Surgery,RambamHealthCareCampus,Haifa,Israel.12DivisionofTrauma Surgery,HospitaldeClinicas-,SchoolofMedicalSciences,Universityof Campinas,Campinas,Brazil.13DepartmentofSurgery,UniversidaddelValle, FundacionValledelLili,Cali,Colombia.14DepartmentofSurgery,PtBDS Post-graduateInstituteofMedicalSciences,Rohtak,India.15Departmentof Surgery1,LvivRegionalHospital,DanyloHalytskyLvivNationalMedical University,Lviv,Ukraine.16DepartmentofSurgery,YonseiUniversityCollege ofMedicine,Seoul,Korea.17DepartmentofAnesthesiology,Macerata Hospital,Macerata,Italy.18DepartmentofSurgery,UniversityHospital Southampton,Southampton,UK. Received:21February2014Accepted:25February2014 Published:27March2014 References1.MazuskiJE,SolomkinJS: Intra-abdominalinfections. SurgClinNorthAm 2009, 89 (2):421 – 437. 2.BabinchakT,Ellis-GrosseE,DartoisN,RoseGM,LohE: Theefficacyand safetyoftigecyclineforthetreatmentofcomplicatedintra-abdominal infections:analysisofpooledclinicaldata. ClinInfectDis 2005, 41 (Suppl5):S354 – S367. 3.MerlinoJI,MalangoniMA,SmithCM,LangeRL: Prospectiverandomized trialsaffecttheoutcomesofintraabdominalinfection. AnnSurg 2001, 233 (6):859 – 866. 4.MazuskiJE,SawyerRG,NathensAB,DiPiroJT,ScheinM,KudskKA,YowlerC: Therapeuticagentscommitteeofthesurgicalinfectionssociety.The surgicalinfectionsocietyguidelinesonantimicrobialtherapyforintraabdominalinfections:evidencefortherecommendations. SurgInfect (Larchmt) 2002, 3 (3):175 – 233. 5.SartelliM,CatenaF,AnsaloniL,LeppaniemiA,TavilogluK,vanGoorH,Viale P,LazzareschiDV,CoccoliniF,CorbellaD,deWerraC,MarrelliD,ColizzaS, ScibR,AlisH,TorerN,NavarroS,SakakushevB,MassalouD,AugustinG, CataniM,KauhanenS,PletinckxP,KenigJ,diSaverioS,JovineE,Guercioni G,SkrovinaM,Diaz-NietoR,FerreroA, etal : Complicatedintra-abdominal infectionsinEurope:acomprehensivereviewoftheCIAOstudy. WorldJEmergSurg 2012, 7 (1):36. 6.LaRosaSP: Sepsis:Menuofnewapproachesreplacesonetherapyforall. CleveClinJMed 2002, 69: 65 – 73. 7.LevyMM,FinkMP,MarshallJC,AbrahamE,AngusD,CookD,CohenJ, OpalSM,VincentJL,RamsayG: SCCM/ESICM/ACCP/ATS/SISinternational sepsisdefinitionsconference. CritCareMed 2001, 2003 (31):1250 – 1256. 8.BoneRC,BalkRA,CerraFB,DellingerRP,FeinAM,KnausWA,ScheinRM, SibbaldWJ: Americancollegeofchestphysicians/societyofcriticalcare medicineconsensusconference:definitionsforsepsisandorganfailure andguidlinesfortheuseofinnovativetherapiesinsepsis. Chest 1992, 101: 1644 – 1655. 9.JonesAE,YiannibasV,JohnsonC,KlineJA: Emergencydepartment hypotensionpredictssuddenunexpectedin-hospitalmortality:a prospectivecohortstudy. Chest 2006, 130: 941 – 946. 10.EstebanA,Frutos-VivarF,FergusonND,PeuelasO,LorenteJA,GordoF, HonrubiaT,AlgoraA,BustosA,GarcaG,Diaz-ReganIR,deLunaRR: Sepsisincidenceandoutcome:contrastingtheintensivecareunitwith thehospitalward. CritCareMed 2007, 35 (5):1284 – 1289. 11.DellingerRP,LevyMM,RhodesA,AnnaneD,GerlachH,OpalSM,Sevransky JE,SprungCL,DouglasIS,JaeschkeR,OsbornTM,NunnallyME,Townsend SR,ReinhartK,KleinpellRM,AngusDC,DeutschmanCS,MachadoFR, RubenfeldGD,WebbS,BealeRJ,VincentJL,MorenoR: Survivingsepsis campaignguidelinescommitteeincludingthepediatricsubgroup. Survivingsepsiscampaign:internationalguidelinesformanagementofseveresepsisandsepticshock,2012. IntensiveCareMed 2013, 39 (2):165 – 228. 12.TsukadaK,KatohH,ShiojimaM,SuzukiT,TakenoshitaS,NagamachiY: Concentrationsofcytokinesinperitonealfluidafterabdominalsurgery. EurJSurg 1993, 159: 475 – 479. 13.PatelRT,DeenKI,YoungsD,WarwickJ,KeighleyMR: Interleukin6isa prognosticindicatorofoutcomeinsevereintra-abdominalsepsis. BrJSurg 1994, 81: 1306 – 1308. 14.DamasP,LedouxD,NysM,VrindtsY,deGrooteD,FranchimontP,LamyM: Cytokineserumlevelduringseveresepsisinhuman.Il6asamarkerof severity. AnnSurg 1992, 215: 356 – 362. 15.HolzheimerRG,ScheinM,WittmannDH: Inflammatoryresponsein peritonealexudateandplasmaofpatientsundergoingplanned relaparotomyforseveresecondaryperitonitis. ArchSurg 1995, 130: 1314 – 1319. 16.CavaillonJM,MunozC,FittingC,MissetB,CarletJ: Circulatingcytokines: thetipoftheiceberg? CircShock 1992, 38 (2):145 – 152. 17.MartineauL,ShekPN: Peritonealcytokineconcentrationsandsurvival outcomeinanexperimentalbacterialinfusionmodelofperitonitis. CritCareMed 2000, 28 (3):788 – 794. 18.HendriksT,BleichrodtRP,LommeRM,deManBM,vanGoorH,BuyneOR: Peritonealcytokinespredictmortalityaftersurgicaltreatmentof secondaryperitonitisintherat. JAmCollSurg 2010, 211: 263 – 270. 19.RichF,GayatE,ColletC,MatoJ,LaisnMJ,LaunayJM,ValleurP,PayenD, CholleyBP: Localandsystemicinnateimmuneresponsetosecondary humanperitonitis. CritCare 2013, 17 (5):R201. 20.AngusDC,vanderPollT: Severesepsisandsepticshock. NEnglJMed 2013, 369 (9):840 – 851. 21.SartelliM,VialeP,CatenaF,AnsaloniL,MooreE,MalangoniM,MooreFA, VelmahosG,CoimbraR,IvaturyR,PeitzmanA,KoikeK,LeppaniemiA,Biffl W,BurlewCC,BaloghZJ,BoffardK,BendinelliC,GuptaS,KlugerY,Agresta F,diSaverioS,WaniI,EscalonaA,OrdonezC,FragaGP,JuniorGA,BalaM, CuiY,MarwahS, etal : 2013WSESguidelinesformanagementof intra-abdominalinfections. WorldJEmergSurg 2013, 8 (1):3. doi:10.1186/1749-7922-8-3. 22.EmmiV,SgangaG: Diagnosisofintra-abdominalinfections:clinical findingsandimaging. InfezMed 2008,16 (Suppl1):19 – 30. 23.JaramilloEJ,TrevioJM,BerghoffKR,FranklinMEJr: Bedsidediagnostic laparoscopyintheintensivecareunit:a13-yearexperience. JSLS 2006, 10 (2):155 – 159. 24.CeribelliC,AdamiEA,MattiaS,BeniniB: Bedsidediagnosticlaparoscopy forcriticallyillpatients:aretrospectivestudyof62patients. SurgEndosc 2012, 26 (12):3612 – 5. 25.ShaniV,MuchtarE,KarivG,RobenshtokE,LeiboviciL: Systematicreview andmeta-analysisoftheefficacyofappropriateempiricantibiotic therapyforsepsis. AntimicrobAgentsChemother 2010, 54 (11):4851 – 4863. 26.FerrerR,ArtigasA,SuarezD,PalenciaE,LevyMM,ArenzanaA,PrezXL, SirventJM,EdusepsisStudyGroup: Edusepsisstudygroup:effectiveness oftreatmentsforseveresepsis:aprospective,multicenter,observational study. AmJRespirCritCareMed 2009, 180: 861 – 866. 27.Castellanos-OrtegaA,SuberviolaB,Garca-AstudilloLA,HolandaMS,OrtizF, LlorcaJ,Delgado-RodrguezM: Impactofthesurvivingsepsiscampaign protocolsonhospitallengthofstayandmortalityinsepticshock patients:resultsofathree-yearfollow-upquasi-experimentalstudy. CritCareMed 2010, 38: 1036 – 1043. 28.PuskarichMA,TrzeciakS,ShapiroNI,rnoldRC,HortonJM,StudnekJR,Kline JA,JonesAE,EmergencyMedicineShockResearchNetwork(EMSHOCKNET): Emergencymedicineshockresearchnetwork(EMSHOCKNET): associationbetweentimingofantibioticadministrationandmortality fromsepticshockinpatientstreatedwithaquantitativeresuscitation protocol. CritCareMed 2011, 39: 2066 – 2071. 29.RichFC,DrayX,LaisnMJ,MatoJ,RaskineL,Sanson-LePorsMJ,PayenD, ValleurP,CholleyBP: Factorsassociatedwithsepticshockandmortality ingeneralizedperitonitis:comparisonbetweencommunity-acquiredand postoperativeperitonitis. CritCare 2009, 13 (3):R99.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page13of16 http://www.wjes.org/content/9/1/22

PAGE 14

30.FryD: Thegenericresponse. CritCareMed 2008, 36: 1369 – 1370. 31.TangBM,McLeanAS,DawesIW,HuangSJ,CowleyMJ,LinRC: Gene-expressionprofilingofgram-positiveandgram-negativesepsisin criticallyillpatients. CritCareMed 2008, 36: 1125 – 1128. 32.MontraversP,AndremontA,MassiasL,CarbonC: Investigationofthe potentialroleofEnterococcusfaecalisinthepathophysiologyof experimentalperitonitis. JInfectDis 1994, 169: 821 – 830. 33.MontraversP,MohlerJ,SaintJulienL,CarbonC: Evidenceofthe proinflammatoryroleofenterococcusfaecalisinpolymicrobial peritonitisinrats. InfectImmun 1997, 65: 144 – 149. 34.HffkenG,NiedermanM: Nosocomialpneumonia.Theimportanceofa de-escalatingstrategyforantibiotictreatmentofpneumoniaintheICU. Chest 2002, 122: 2183 – 2196. 35.RelloJ,VidaurL,SandiumengeA,RodrguezA,GualisB,BoqueC,DiazE: De-escalationtherapyinventilator-associatedpneumonia. CritCareMed 2004, 32: 2183 – 2190. 36.PeaF,VialeP: Bench-to-bedsidereview:appropriateantibiotictherapyin severesepsisandsepticshock – doesthedosematter? CritCare 2009, 13 (3):214. 37.HatalaR,DinhT,CookDJ: Once-dailyaminoglycosidedosingin immunocompetentadults:ameta-analysis. AnnInternMed 1996, 124: 717 – 725. 38.McKenzieC: Antibioticdosingincriticalillness. JAntimicrobChemother 2011, 66 (Suppl2):ii25 – ii31. 39.RobertsJA,LipmanJ,BlotS,RelloJ: Betteroutcomesthroughcontinuous infusionoftime-dependentantibioticstocriticallyillpatients? CurrOpin CritCare 2008, 14 (4):390 – 396. 40.SolomkinJS,MazuskiJE,BradleyJS,RodvoldKA,GoldsteinEJ,BaronEJ, O ’ NeillPJ,ChowAW,DellingerEP,EachempatiSR,GorbachS,HilfikerM, MayAK,NathensAB,SawyerRG,BartlettJG: Diagnosisandmanagement ofcomplicatedintra-abdominalinfectioninadultsandchildren: guidelinesbytheSurgicalInfectionSocietyandtheInfectiousDiseases SocietyofAmerica. ClinInfectDis 2010, 50 (2):133 –164. 41.PowellLL,WilsonSE: Theroleofbeta-lactamantimicrobialsassingle agentsintreatmentofintra-abdominalinfection. SurgInfect(Larchmt) 2000, 1 (1):57 – 63. 42.Al-HasanMN,LahrBD,Eckel-PassowJE,BaddourLM: Antimicrobialresistance trendsofEscherichiacolibloodstreamisolates:apopulation-basedstudy, 1998 – 2007. JAntimicrobChemother 2009, 64 (1):169 – 174. 43.JonesRN,HuynhHK,BiedenbachDJ,FritscheTR,SaderHS: Doripenem (S-4661),anovelcarbapenem:comparativeactivityagainst contemporarypathogensincludingbactericidalactionandpreliminary invitromethodsevaluations. JAntimicrobChemother 2004, 54 (1):144 – 154. 44.BrownSD,TraczewskiMM: Comparativeinvitroantimicrobialactivityofa newcarbapenem,doripenem:tentativediscdiffusioncriteriaandquality control. JAntimicrobChemother 2005, 55 (6):944 – 949. 45.MichalopoulosAS,KaratzaDC: Multidrug-resistantGram-negative infections:theuseofcolistin. ExpertRevAntiInfectTher 2010, 8 (9):1009 – 1017. 46.PapaparaskevasJ,TzouvelekisLS,TsakrisA,PittarasTE,LegakisNJ: Hellenic tigecyclinestudygroup:invitroactivityoftigecyclineagainst2423 clinicalisolatesandcomparisonoftheavailableinterpretation breakpoints. DiagnMicrobiolInfectDis 2010, 66 (2):187 – 194. 47.SekowskaA,GospodarekE: SusceptibilityofKlebsiellaspp.totigecycline andotherselectedantibiotics. MedSciMonit 2010, 16 (6):BR193 – BR196. 48.SteinGE,BabinchakT: Tigecycline:anupdate. DiagnMicrobiolInfectDis 2013, 75 (4):331 – 336. 49.USFoodandDrugAdministration: FDAdrugsafetycommunication: increasedriskofdeathwithTygacil(tigecycline)comparedtoother antibioticsusedtotreatsimilarinfections[online]. AvailablefromURL: http://www.fda.gov/Drugs/DrugSafety/ucm224370.htm. 50.SteinGE,SmithCL,MissavageA,SaundersJP,NicolauDP,BattjesSM, KeprosJP: Tigecyclinepenetrationintoskinandsofttissue. SurgInfect (Larchmt) 2011, 12 (6):465 – 467. 51.ZoniosDI,BennettJE: Updateonazoleantifungals. SeminRespirCritCare Med 2008, 29 (2):198– 210. 52.PfallerMA,DiekemaDJ: Epidemiologyofinvasivecandidiasis:apersistent publichealthproblem. ClinMicrobiolRev 2007, 20: 133 – 163. 53.GlocknerA: Treatmentandprophylaxisofinvasivecandidiasiswith anidulafungin,caspofunginandmicafungin:reviewoftheliterature. EurJMedRes 2011, 16 (4):167 – 179. 54.ChenSC,SlavinMA,SorrellTC: Echinocandinantifungaldrugsinfungal infections:acomparison. Drugs 2011, 71 (1):11 – 41. 55.Ostrosky-ZeichnerL,RexJH,PappasPG,HamillRJ,LarsenRA,HorowitzHW, PowderlyWG,HyslopN,KauffmanCA,ClearyJ,ManginoJE,LeeJ: Antifungalsusceptibilitysurveyof2,000bloodstreamCandidaisolatesin theUnitedStates. AntimicrobAgentsChemother 2003, 47: 3149 – 3154. 56.KarimovaA,PinskyDJ: Theendothelialresponsetooxygeneprivation: biologyandclinicalimplications. IntensiveCareMed 2001, 27: 19 – 31. 57.BenjaminE,LeibowitzAB,OropelloJ,IbertiTJ: Systemichypoxicand inflammatorysyndrome:Analternativedesignationfor “ sepsis syndrome ” CritCareMed 1992, 20: 680 – 682. 58.RiversE: Earlygoal-directedtherapyinthetreatmentofseveresepsis andsepticshock. NEngJMed 2001, 345: 1368 – 1377. 59.AduenJ,BernsteinWK,KhastgirT,MillerJ,KerznerR,BhatianiA,MillerJ, KerznerR,BhatianiA,LustgartenJ,BassinAS,DavisonL,ChernowB: Theuse andclinicalimportanceofasubstrate-specificelectrodeforrapid determinationofbloodlactateconcentrations. JAMA 1994, 272: 1678 – 1685. 60.MikkelsenME,MiltiadesAN,GaieskiDF,GoyalM,FuchsBD,ShahCV, BellamySL,ChristieJD: Serumlactateisassociatedwithmortalityin severesepsisindependentoforganfailureandshock. CritCareMed 2009, 37: 1670 – 1677. 61.TrzeciakS,DellingerRP,ChanskyME,ArnoldRC,SchorrC,MilcarekB, HollenbergSM,ParrilloJE: Serumlactateasapredictorofmortalityin patientswithinfection. IntensiveCareMed 2007, 33: 970 – 977. 62.ShapiroNI,HowellMD,TalmorD,NathansonLA,LisbonA,WolfeRE,WeissJW:Serumlactateasapredictorofmortalityinemergencydepartment patientswithinfection. AnnEmergMed 2005, 45: 524 – 528. 63.PearseRM: Extendingtheroleoflactatemeasurementintothe prehospitalenvironment. CritCare 2009, 13: 115. 64.NguyenHB,RiversEP,KnoblichBP,JacobsenG,MuzzinA,ResslerJA, TomlanovichMC: Earlylactateclearanceisassociatedwithimproved outcomeinseveresepsisandsepticshock. CritCareMed 2004, 32: 1637 – 1642. 65.JamesJH,LuchetteFA,McCarterFD,FischerJE: Lactateisan unreliableindicatoroftissuehypoxiaininjuryorsepsis. Lancet 1999, 354: 505 – 508. 66.DugasD,MackenhauerJ,JoyceN,DonninoM: Prevalenceand characteristicsofnonlactateandlactateexpressorsinsepticshock. CritCareMed 2009, 37 (Suppl):A227. 67.CannonCM,fortheMulticenterSevereS,SepticShockCollaborativeG.The GENESISProject(GENeralizationofEarlySepsisInterventionS): Amulticenter qualityimprovementcollaborative. AcadEmergMed 2010, 17: 1258. 68.PerelP,RobertsI: Colloidsversuscrystalloidsforfluidresuscitationin criticallyillpatients. CochraneDatabaseSystRev 2011, 3: CD000567. 69.WalkerJ,CriddleLM: Pathophysiologyandmanagementofabdominal compartmentsyndrome. AmJCritCare 2003, 12 (4):367 – 371. 70.BrandtS,RegueiraT,BrachtH,PortaF,DjafarzadehS,TakalaJ,GorrasiJ, BorottoE,KrejciV,HiltebrandLB,BrueggerLE,BeldiG,WilkensL,Lepper PM,KesslerU,JakobSM: Effectoffluidresuscitationonmortalityand organfunctioninexperimentalsepsismodels. CritCare 2009, 13 (6):R186. 71.HarveyS,YoungD,BramptonW,CooperAB,DoigG,SibbaldW,RowanK: Pulmonaryarterycathetersforadultpatientsinintensivecare. CochraneDatabaseSystRev 2006, 19 (3),CD003408. 72.CharronC,CailleV,Jar dinF,Vieillard-BaronA: Echocardiographicmeasurement offluidresponsiveness. CurrOpinCritCare 2006, 12 (3):249 – 254. 73.ManasiaAR,NagarajHM,KodaliRB,CroftLB,OropelloJM,Kohli-SethR, LeibowitzAB,DelGiudiceR,HufandaJF,BenjaminE,GoldmanME: Feasibilityandpotentialclinicalutilityofgoal-directedtransthoracic echocardiographyperformedbynoncardiologistintensivistsusinga smallhand-carrieddevice(SonoHeart)incriticallyillpatients. JCardiothoracVascAnesth 2005, 19 (2):155 – 9. 74.ZhangZ,XuX,YaoM,ChenH,NiH,FanH: UseofthePiCCOsystemin criticallyillpatientswithsepticshockandacuterespiratorydistress syndrome:astudyprotocolforarandomizedcontrolledtrial.Trials 2013, 14: 32. 75.MartinC,PapazianL,PerrinG,SauxP,GouinF: Norepinephrineor dopamineforthetreatmentofhyperdynamicsepticshock? Chest 1993, 103 (6):1826 – 1831. 76.deBackerD,AldecoaC,NjimiH,VincentJL: Dopamineversus norepinephrineinthetreatmentofsepticshock:ameta-analysis*. CritCareMed 2012, 40 (3):725 – 730.Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page14of16 http://www.wjes.org/content/9/1/22

PAGE 15

77.RegnierB,RapinM,GoryG,LemaireF,TeisseireB,HarariA: Haemodynamic effectsofdopamineinsepticshock. IntensiveCareMed 1977, 3: 47 – 53. 78.SeguinP,BellissantE,LeTulzoY,LaviolleB,LessardY,ThomasR,Malldant Y: Effectsofepinephrinecomparedwiththecombinationofdobutamine andnorepinephrineongastricperfusioninsepticshock. ClinPharmacol Ther 2002, 71: 381 – 388. 79.MyburghJA,HigginsA,JovanovskaA,CATStudyinvestigators: Acomparisonofepinephrineandnorepinephrineincriticallyillpatients. IntensiveCareMed 2008, 34: 2226 – 2234. 80.HolmesCL,PatelBM,RussellJA,WalleyKR,WalleyKR: Physiologyof vasopressinrelevanttomanagementofsepticshock. Chest 2001, 120: 989 – 1002. 81.WhiteLE,HassounHT,BihoracA,MooreLJ,SailorsRM,McKinleyBA,Valdivia A,MooreFA: Acutekidneyinjuryissurprisinglycommonandapowerful predictorofmortalityinsurgicalsepsis. JTraumaAcuteCareSurg 2013, 75 (3):432 – 438. 82.MarshallJC: Principlesofsourcecontrolintheearlymanagementof sepsis. CurrInfectDisRep 2010, 12 (5):345 – 353. 83.MarshallJC,alNaqbiA: Principlesofsourcecontrolinthemanagement ofsepsis. CritCareClin 2009, 25 (4):753 – 768. 84.WachaH,HauT,DittmerR,OhmannC: Riskfactorsassociatedwith intraabdominalinfections:aprospectivemulticenterstudy.Peritonitis studygroup. langenbecksArchSurg 1999, 384: 24 – 32. 85.SugimotoK,HirataM,KikunoT,TakishimaT,MaekawaK,OhwadaT: Large-volumeintraoperativeperitoneallavagewithanassistantdevice fortreatmentofperitonitiscausedbyblunttraumaticruptureofthe smallbowel. JTrauma 1995, 39 (4):689 – 692. 86.LopezN,KobayashiL,CoimbraR: AComprehensivereviewofabdominal infections. WorldJEmergSurg 2011, 6: 7. 87.AgrestaF,CiardoLF,MazzaroloG,MicheletI,OrsiG,TrentinG,BedinN: Peritonitis:laparoscopicapproach. WorldJEmergSurg 2006, 24: 1 – 9. 88.AndersonID,FearonKC,GrantIS: Laparotomyforabdominalsepsisinthe criticallyill.BrJSurg 1996, 83 (4):535 – 539. 89.KopernaT,SemmlerD,MarianF: Riskstratificationinemergencysurgical patients:istheAPACHEIIscoreareliablemarkerofphysiological impairment? ArchSurg 2001, 136 (1):55 – 59. 90.vanRulerO,KiewietJJ,BoerKR,LammeB,GoumaDJ,BoermeesterMA, ReitsmaJB: Failureofavailablescoringsystemstopredictongoing infectioninpatientswithabdominalsepsisaftertheirinitialemergency laparotomy. BMCSurg 2011, 23: 11 – 38. 91.KopernaT,SchulzF: Relaparotomyinperitonitis:prognosisandtreatment ofpatientswithpersistingintraabdominalinfection. WorldJSurg 2000, 24 (1):32 – 37. 92.vanRulerO,LammeB,deVosR,ObertopH,ReitsmaJB,BoermeesterMA: Decisionmakingforrelaparotomyinsecondaryperitonitis. DigSurg 2008, 25 (5):339 – 346. 93.LammeB,MahlerCW,vanRulerO,GoumaDJ,ReitsmaJB,BoermeesterMA: Clinicalpredictorsofongoinginfectioninsecondaryperitonitis: systematicreview. WorldJSurg 2006, 30 (12):2170 – 2181. 94.HinsdaleJG,JaffeBM: Re-operationforintra-abdominalsepsis.Indications andresultsinmoderncriticalcaresetting. AnnSurg 1984, 199 (1):31 – 36. 95.HutchinsRR,GunningMP,LucasDN,Allen-MershTG,SoniNC: Relaparotomy forsuspectedintraperitonealsepsisafterabdominalsurgery. WorldJSurg 2004, 28 (2):137 – 141. 96.vanRulerO,LammeB,GoumaDJ,ReitsmaJB,BoermeesterMA: Variables associatedwithpositivefindingsatrelaparotomyinpatientswith secondaryperitonitis. CritCareMed 2007, 35 (2):468 – 476. 97.HolzheimerRG,GathofB: Re-operationforcomplicatedsecondary peritonitis-howtoidentifypatientsatriskforpersistentsepsis. EurJMed Res 2003, 8 (3):125 – 134. 98.vanRulerO,MahlerCW,BoerKR,ReulandEA,GooszenHG,OpmeerBC, deGraafPW,LammeB,GerhardsMF,StellerEP,vanTillJW,deBorgieCJ, GoumaDJ,ReitsmaJB,BoermeesterMA: Comparisonofon-demandvs plannedrelaparotomystrategyinpatientswithsevereperitonitis:a randomizedtrial. JAMA 2007, 298: 865 – 872. 99.RobledoFA,Luque-de-LenE,SurezR,SnchezP,de-la-FuenteM,VargasA,MierJ: Openversusclosedmanagementoftheabdomeninthesurgical treatmentofseveresecondaryperitonitis:arandomizedclinicaltrial. SurgInfect(Larchmt) 2007, 8: 63 – 72. 100.KirkpatrickAW,RobertsDJ,deWaeleJ,JaeschkeR,MalbrainML,de KeulenaerB,DuchesneJ,BjorckM,LeppaniemiA,EjikeJC,SugrueM, CheathamM,IvaturyR,BallCG,ReintamBlaserA,RegliA,BaloghZJ, D ’ AmoursS,DeberghD,KaplanM,KimballE,OlveraC: PediatricGuidelines Sub-CommitteefortheWorldSocietyoftheAbdominalCompartment Syndrome.Intra-abdominalhypertensionandtheabdominalcompartment syndrome:updatedconsensusdefinitionsandclinicalpracticeguidelines fromtheWorldSocietyoftheAbdominalCompartmentSyndrome. IntensiveCareMed 2013, 39 (7):1190 – 1206. 101.MerrellRC: Theabdomenassourceofsepsisincriticallyillpatients. CritCareClin 1995, 11 (2):255 – 272. 102.WaibelBH,RotondoMF: Damagecontrolintraumaandabdominal sepsis. CritCareMed 2010, 38 (9Suppl):S421 – S430. 103.JansenJO,LoudonMA: Damagecontrolsurgeryinanon-traumasetting. BrJSurg 2007, 94 (7):789 – 790. 104.AminAI,ShaikhIA: Topicalnegativepressureinmanagingsevere peritonitis:apositivecontribution? WorldJGastroenterol 2009, 15 (27):3394 – 3397. 105.SchmelzleM,AlldingerI,MatthaeiH,AydinF,WallertI,EisenbergerCF, SchulteAmEschJ2nd,DizdarL,ToppSA,YangQ,KnoefelWT: Long-term vacuum-assistedclosureinopenabdomenduetosecondaryperitonitis: aretrospectiveevaluationofaselectedgroupofpatients. DigSurg 2010, 27 (4):272 – 278. 106.ScheinM: Plannedreoperationsandopenmanagementincritical intra-abdominalinfections:prospectiveexperiencein52cases. WorldJ Surg 1991, 15: 537 – 545. 107.AdkinsAL,RobbinsJ,VillalbaM,BendickP,ShanleyCJ: Openabdomen managementofintra-abdominalsepsis. AmSurg 2004, 70: 137 – 140. 108.HorwoodJ,AkbarF,MawA: Initialexperienceoflaparostomywith immediatevacuumtherapyinpatientswithsevereperitonitis. AnnRColl SurgEngl 2009, 91 (8):681 – 687. 109.DemetriadesD: Totalmanagementoftheopenabdomen. IntWoundJ 2012, 9(Suppl1):17 – 24. 110.PaulJS,RidolfiTJ: Acasestudyinintra-abdominalsepsis. SurgClinNorth Am 2012, 92 (6):1661 – 1677. 111.RotondoMF,SchwabCW,McGonigalMD,PhillipsGR3rd,FruchtermanTM, KauderDR,LatenserBA,AngoodPA: ‘ Damagecontrol ’ :anapproachfor improvedsurvivalinexsanguinatingpenetratingabdominalinjury. JTrauma 1993, 35 (3):375 – 382. 112.GodatL,KobayashiL,CostantiniT,CoimbraR: Abdominaldamagecontrol surgeryandreconstruction:Worldsocietyofemergencysurgery positionpaper. WorldJEmergSurg 2013, 8 (1):53. 113.WaibelBH,RotondoMM: Damagecontrolsurgery:it ’ sevolutionoverthe last20years. RevColBrasCir 2012, 39 (4):314 – 321. 114.MooreLJ,MooreFA: Epidemiologyofsepsisinsurgicalpatients. SurgClin NorthAm 2012, 92 (6):1425 – 1443. 115.OrdoezCA,PinoLF,BadielM,SnchezAI,LoaizaJ,BallestasL,PuyanaJC: Safetyofperformingadelayedanastomosisduringdamagecontrol laparotomyinpatientswithdestructivecoloninjuries. JTrauma 2011, 71 (6):1512 – 1517. 116.OrdonezCA,SanchezAI,PinedaJA,BadielM,MesaR,CardonaU,AriasR, RossoF,GranadosM,Gutirrez-MartnezMI,OchoaJB,PeitzmanA,PuyanaJC: Deferredprimaryanastomosisversusdiversioninpatientswithsevere secondaryperitonitismanagedwithstagedlaparotomies. WorldJSurg 2010, 34: 169 – 176. 117.PerathonerA,KlausA,MuhlmannG,OberwalderM,MargreiterR, Kafka-Ritsch,OberwalderM,MargreiterR,Kafka-RitschQ: Damagecontrol withabdominalvacuumtherapy(VAC)tomanageperforateddiverticulitis withadvancedgeneralizedperitonitis – aproofofconcept. IntJ ColorectalDis 2010, 25: 767 – 774. 118.Kafka-RitschR,BirkfellnerF,PerathonerA,RaabH,NehodaH, PratschkeJ,ZittM: Damagecontrolsurgerywithabdominalvacuum anddelayedbowelreconstructioninpatientswithperforated diverticulitisHincheyIII/IV. JGastroenterolSurg 2012, 16: 1915 – 1922. 119.YuanY,RenJ,HeY: Currentstatusoftheopenabdomentreatmentfor intra-abdominalinfection. GastroenterolResPract 2013 : 532013.Epub2013 Oct2.120.RegnerJL,KobayashiL,CoimbraR: Surgicalstrategiesformanagementof theopenabdomen. WorldJSurg 2012, 36 (3):497 – 510. 121.PadalinoP,DionigiG,MinojaG,CarcanoG,RoveraF,BoniL,DionigiR: Fascia-to-fasciaclosurewithabdominaltopicalnegativepressurefor severeabdominalinfections:preliminaryresultsinadepartmentofSartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page15of16 http://www.wjes.org/content/9/1/22

PAGE 16

generalsurgeryandintensivecareunit. SurgInfect(Larchmt) 2010, 11 (6):523 – 528. 122.TsueiBJ,SkinnerJC,BernardAC,KearneyPA,BoulangerBR: Theopen peritonealcavity:etiologycorrelateswiththelikelihoodoffascial closure. AmSurg 2004, 70 (7):652 – 656. 123.PliakosI,PapavramidisTS,MihalopoulosN,KoulourisH,KesisoglouI, SapalidisK,DeligiannidisN,PapavramidisS: Vacuum-assistedclosurein severeabdominalsepsiswithorwithoutretentionsuturedsequential fascialclosure:aclinicaltrial. Surgery 2010, 148 (5):947 – 953. 124.RobertsDJ,ZygunDA,GrendarJ,BallCG,RobertsonHL,OuelletJF, CheathamML,KirkpatrickAW: Negative-pressurewoundtherapyfor criticallyilladultswithopenabdominalwounds:asystematicreview. JTraumaAcuteCareSurg 2012, 73 (3):629 – 639. 125.KubiakBD,AlbertSP,GattoLA,SnyderKP,MaierKG,VieauCJ,RoyS, NiemanGF: Peritonealnegativepressuretherapypreventsmultiple organinjuryinachronicporcinesepsisandischemia/reperfusionmodel. Shock 2010, 34: 525 – 534. 126.PlaudisH,RudzatsA,MelbergaL,KazakaI,SubaO,PupelisG: Abdominal negative-pressuretherapy:anewmethodincounteringabdominal compartmentandperitonitis-prospectivestudyandcriticalreviewof literature. AnnIntensiveCare 2012, 20 (2Suppl1):S23. 127.BoelevanHensbroekP,WindJ,DijkgraafMG,BuschOR,GoslingsJC: Temporaryclosureoftheopenabdomen:asystematicreviewon delayedprimaryfascialclosureinpatientswithanopenabdomen. WorldJSurg 2009, 33 (2):199 – 207. 128.RasilainenSK,MentulaPJ,LeppniemiAK: Vacuumandmesh-mediated fascialtractionforprimaryclosureoftheopenabdomenincriticallyill surgicalpatients. BrJSurg 2012, 99 (12):1725 – 1732. 129.KissaneNA,ItaniKM: Adecadeofventralincisionalherniarepairswith biologicacellulardermalmatrix:whathavewelearned? PlastReconstr Surg 2012, 130 (5Suppl2):194S – 202S. 130.DellingerRP,LevyMM,CarletJM,BionJ,ParkerMM,JaeschkeR,ReinhartK, AngusDC,Brun-BuissonC,BealeR,CalandraT,DhainautJF,GerlachH, HarveyM,MariniJJ,MarshallJ,RanieriM,RamsayG,SevranskyJ,Thompson BT,TownsendS,VenderJS,ZimmermanJL,VincentJL,International SurvivingSepsisCampaignGuidelinesCommittee;AmericanAssociationof Critical-CareNurses;AmericanCollegeofChestPhysicians;AmericanCollege ofEmergencyPhysicians;CanadianCriticalCareSociety;EuropeanSociety ofClinicalMicrobiologyandInfectiousDiseases;EuropeanSocietyof IntensiveCareMedicine;EuropeanRespiratorySociety;InternationalSepsis Forum;JapaneseAssociationforAcuteMedicine;JapaneseSocietyof IntensiveCareMedicine;SocietyofCriticalCareMedicine;Societyof HospitalMedicine;SurgicalInfectionSociety;WorldFederationofSocieties ofIntensiveandCriticalCareMedicine: SurvivingSepsisCampaign: Internationalguidelinesformanagementofseveresepsisandseptic shock. CritCareMed 2008, 36: 296 – 327. 131.BernardGR,VincentJL,LaterrePF,LaRosaSP,DhainautJF,Lopez-Rodriguez A,SteingrubJS,GarberGE,HelterbrandJD,ElyEW,FisherCJJr: Recombinant humanproteinCWorldwideEvaluationinSevereSepsis(PROWESS)studygroup.EfficacyandsafetyofrecombinanthumanactivatedproteinCfor severesepsis. NEnglJMed 2001, 344: 699 – 709. 132.HodderRV,HallR,RussellJA,FisherHN,LeeB: Earlydrotrecoginalpha (activated)administrationinseveresepsisisassociatedwithlower mortality:aretrospectiveanalysisoftheCanadianENHANCEcohort. CritCare 2009, 13 (3):R78. 133.FinferS,RanieriVM,ThompsonBT,BariePS,DhainautJF,DouglasIS, GrdlundB,MarshallJC,RhodesA: Design,conduct,analysisand reportingofamulti-nationalplacebo-controlledtrialofactivatedprotein Cforpersistentsepticshock. IntensiveCareMed 2008, 34 (11):1935 – 1947. 134.SavelRH,MunroCL: Evidence-basedbacklash:thetaleofdrotrecogin alfa. AmJCritCare 2012, 21 (2):81 – 83. 135.AnnaneD,BellissantE,BollaertPE,BriegelJ,ConfalonieriM,deGaudioR, KehD,KupferY,OppertM,MeduriGU: Corticosteroidsinthetreatmentof severesepsisandsepticshockinadults:asystematicreview. JAMA 2009, 301 (22):2362 – 2375. 136.AnnaneD: Corticosteroidsforseveresepsis:anevidence-basedguidefor physicians. AnnIntensiveCare 2011, 1 (1):7. 137.CohenJ,ChinwD: Nutritionandsepsis. WorldRevNutrDiet 2013, 105: 116 – 125. 138.MarikPE,ZalogaGP: Earlyenteralnutritioninacutelyillpatients:a systematicreview. CritCareMed 2001, 29: 2264 – 2270. 139.HeylandDK,DhaliwalR,DroverJW,GramlichL,DodekP: Canadiancritical careclinicalpracticeguidelinescommittee:Canadianclinicalpractice guidelinesfornutritionsupportinmechanicallyventilated,criticallyill adultpatients. JPENJParenterEnteralNutr 2003, 27: 355 – 373. 140.DoigGS,HeighesPT,SimpsonF,SweetmanEA,DaviesAR: Earlyenteral nutrition,providedwithin24hofinjuryorintensivecareunitadmission, significantlyreducesmortalityincriticallyillpatients:ameta-analysisof randomisedcontrolledtrials. IntensiveCareMed 2009, 35: 2018 – 2027.doi:10.1186/1749-7922-9-22 Citethisarticleas: Sartelli etal. : Currentconceptofabdominalsepsis: WSESpositionpaper. WorldJournalofEmergencySurgery 2014 9 :22. Submit your next manuscript to BioMed Central and take full advantage of: € Convenient online submission € Thorough peer review € No space constraints or color “gure charges € Immediate publication on acceptance € Inclusion in PubMed, CAS, Scopus and Google Scholar € Research which is freely available for redistribution Submit your manuscript at www.biomedcentral.com/submit Sartelli etal.WorldJournalofEmergencySurgery 2014, 9 :22Page16of16 http://www.wjes.org/content/9/1/22