P = 0.90 Hospital stay > 10 days

w w w . e l s e v i e r . c o m / l o c a t e / b j i d

The

Brazilian

Journal

of

INFECTIOUS

DISEASES

Brief

communication

Does

SOFA

predict

outcomes

better

than

SIRS

in

Brazilian

ICU

patients

with

suspected

infection?

A

retrospective

cohort

study

Regis

Goulart

Rosa

,

Rafael

Barberena

Moraes

,

Thiago

Costa

Lisboa

,

Daniel

Pretto

Schunemann

_,

_Cassiano

_Teixeira

a_{HospitalMoinhosdeVento,DepartamentodeCuidadosIntensivos,PortoAlegre,RS,Brazil}

b_{HospitaldeClínicasdePortoAlegre,DepartamentodeCuidadosIntensivos,PortoAlegre,RS,Brazil}

c_{HospitalMoinhosdeVento,DepartamentodeMedicinaInterna,PortoAlegre,RS,Brazil}

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Articlehistory:

Received4July2017 Accepted26September2017 Availableonline13October2017

Keywords:

Sepsis

Intensivecareunit Organdysfunction Outcomes

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Wecomparedthediscriminatorycapacityofthesequentialorganfailureassessment(SOFA) versusthesystemicinflammatoryresponsesyndrome(SIRS)scoreforpredictingICU mor-tality,needforandlengthofmechanicalventilation,ICUstay,andhospitalizationinpatients withsuspectedinfectionadmittedtoamixedBrazilianICU.Weperformedaretrospective analysisofalongitudinalICUdatabasefromatertiaryhospitalinSouthernBrazil.Patients werecategorizedaccordingtowhethertheymetthecriteriaforsepsisaccordingtoSOFA (variation≥2pointsoverthebaselineclinicalcondition)andSIRS(SIRSscore≥2points).

FromJanuary2008toDecember2014,1487patientswereadmittedtotheICUdueto sus-pectedinfection.SOFA≥2identifiedmoreseptic patientsthanSIRS≥2(79.0%[n=1175] vs.68.5%[n=1020],p<0.001).Therewasnodifferencebetweenthetwoscoresin predict-ingICUmortality(areaunderthereceiveroperatingcharacteristiccurve(AUROC)=0.64vs. 0.64,p=0.99).SOFA≥2wasmarginallybetterthanSIRS≥2inpredictingneedfor

mechan-icalventilation(AUROC=0.64vs.0.62,p=0.001),ICUstay>7days(AUROC=0.65vs.0.63,

p=0.004),andlengthofhospitalization>10days(AUROC=0.61vs.0.59,p<0.001).Therewas nodifferencebetweenthetwoscoresinpredictingmechanicalventilation>7days.

©2017SociedadeBrasileiradeInfectologia.PublishedbyElsevierEditoraLtda.Thisisan openaccessarticleundertheCCBY-NC-NDlicense(http://creativecommons.org/licenses/ by-nc-nd/4.0/).

Sepsis results in significant mortality,1–3 _{morbidity, and} resourceutilizationduringandaftercriticalillnesses.4

ThepreviousconsensusdefinitionsofSepsis(Sepsis-1and Sepsis-2)5,6_{reliedonthesystemicinflammatoryresponse}

syn-∗ _{Correspondingauthor.}

E-mailaddress:regis.rosa@hmv.org.br(R.G.Rosa).

drome(SIRS)toinfectionasafundamentalaspectofsepsis diagnosis.In2016,theSepsis-3definitionchangedthefocus from thepresenceofinfection-relatedSIRStothepresence ofinfection-relatedorgandysfunction.7_{Thenewconsensus} wasmainlysupportedbytheretrospectivestudybySeymor etal.,8_{whichshowedthatsequentialorganfailureassessment} (SOFA)resultedinbetterpredictiveaccuracyformortalitythan SIRSamongUSandEuropeanICUpatients.

http://dx.doi.org/10.1016/j.bjid.2017.09.002

However,somehealthcaresocieties9_andexperts10 _have expresseddisappointmentwiththenewrecommendations, mainlyduetothelackofstudiesontheperformanceofthe organ dysfunctionscores indeveloping countries. Thus, to safelyadoptthenewcriteriaproposedbySepsis-3inabroader context,it isnecessary tovalidateit inscenariosdifferent fromthoseoriginallytested.Inaddition,otheroutcomes rele-vanttocriticalcarepatientsbesidesdeathshouldbeassessed. Therefore,weaimedtocomparethediscriminatorycapacity ofSOFAversusSIRSforpredictingrelevantoutcomesamong adultpatientsadmittedtoamixedintensivecareunit(ICU)of atertiaryhospitalinSouthernBrazilduetosuspected infec-tion.

Weperformedaretrospectiveanalysisofacomprehensive prospectivelycollectedlongitudinalICUdatabasecomposed of4221patientsadmittedtothe31-bedmixedICUofHospital MoinhosdeVento,PortoAlegre, Brazil,overa7-yearperiod (January2008toDecember2014).Thisstudywasapprovedby theResearchEthicsCommitteeatHospitalMoinhosdeVento. Theneedforinformedconsentwaswaived.Allpatientswith suspectedinfectionsatICUadmissionwereconsidered eligi-bleforthestudy.Patientswereidentifiedusinginfection,sepsis,

severesepsis,septicshock,pneumonia,urinarytractinfection, blood-streaminfection,intra-abdominalinfection,centralnervoussystem infection, osteoarticularinfection,and skin andsoft tissue infec-tionassearchtermsinthesyndromicdiagnosis fieldofthe database.

Theexposurevariableswerediagnosisofsepsisaccording toSOFAandSIRSdefinitionsatICUadmission.Patientswere classifiedas havingsepsisaccordingtoSOFAif theyhad a scorevariation≥2pointsoverthebaselineclinicalcondition.7

TheSOFAwasassumedtobezeroinpatientsnotknownto havepreexistingorgandysfunction.Inpatientswithchronic organdysfunction,thebaselineSOFAwasassumedtobe4in patientsundergoingchronicrenalreplacementtherapy,and2, 3or4inpatientswithcirrhosis,dependingonbaseline biliru-binlevels.Patientswereclassifiedashavingsepsisaccording toSIRSiftheypresentedatleasttwoofthefollowingsigns ofsystemicinflammation:temperature>38◦_Cor<36◦_C,heart

rate>90 beats per minute,respiratory rate>20 breaths per minuteorPaCO2<32mmHg,abnormalwhitebloodcellcount (>12,000/␮Lor<4000/␮Lor>10%immatureforms).5Inorderto

evaluatetheprognosisofpatientsaccordingtothepresence or absenceoforgan dysfunction (SOFAvariation≥2points

overthebaselineclinicalcondition)andSIRS(SIRSscore≥2

points)wecreatedfourgroups:(1)patientswithorgan dys-functionand SIRS;(2)patientswithSIRSbutwithoutorgan dysfunction;(3)patientswithorgandysfunctionbutwithout SIRS;and(4)patientswithinfection,butwithneitherSIRSnor organdysfunction.

Theoutcomesevaluatedwereall-causeICUmortality,need andlengthofforinvasivemechanicalventilation(MV),length ofICUstay,andlengthofhospitalization.ProlongedMV,ICU stay,and hospitalization weredefined asduration ofthese variablesabovethe75thpercentileofthestudiedpopulation. Theaccuracyofthedifferent sepsisdefinitions for predict-ingtheseoutcomeswasevaluatedthroughtheareaunderthe receiveroperatingcharacteristic(ROC) curve (AUROC). Uni-variatemodelingofthetwodefinitionswascomparedusing

theChi-squaredtest.Acomparisonofoutcomesamongthe study groups was made using the Kruskal–Wallis test for continuousvariablesand thePearson’sChi-squaredtestfor dichotomous variables. Among post hoc tests, Dunn’s test wasappliedaftertheKruskal–Wallistest,andBonferroni cor-rection wasappliedafterthe Pearson’sChi-squared test.A significance level of0.05 was adopted forall comparisons. Statav.12(StataCorpLP,CollegeStation,TX,USA)wasused forstatisticalanalysis.

SOFA≥2identifiedahighernumberofsepticpatientsin

comparisontotheSIRS≥2(79.0%[n=1175]vs.68.5%[n=1020], p<0.001).Baselinecharacteristicsofpatientsaccordingtothe differentdefinitionsofsepsiswere comparable.There were no statistical differences in the proportionofmales (SOFA

≥2, 55.6% vs. SIRS ≥2, 54.0%), median age (SOFA≥2, 75.0

[interquartile range{IQR}, 63.0–83.0]vs. SIRS≥2,75.0 [IQR,

63.0–83.0]), mediannumber ofcomorbidities (SOFA≥2, 3.0

[IQR,2.0–4.0]vs.SIRS≥2,3.0[IQR,2.0–4.0]),median

APACHE-IIscoreatICU admission(SOFA≥2,21.0[IQR,16.0–25.0]vs.

SIRS≥2,21.0[IQR,16.0–26.0]),andmedianSOFAscoreatICU

admission(SOFA≥2,5.0[IQR,3.0–8.0]vs.SIRS≥2:5.0[IQR,

3.0–8.0]).

Acomparisonofthepredictiveaccuracyforthestudy out-comesbetweenSOFA≥2andSIRS≥2isshowninFig.1.SOFA ≥2andSIRS≥2showedsimilardiscriminatorycapacityforICU

mortality(AUROC0.64[0.62–0.67]vs.0.64[0.62–0.67],p=0.99). SOFA≥2hadamarginallybetterdiscriminatorycapacitythan

SIRS≥2forneedforMV(AUROC0.64[95%CI,0.62–0.65]vs.

0.62[95%CI,0.61–0.63],p=0.001),lengthofICUstay>7days (AUROC 0.65 [95%CI,0.63–0.66] vs.0.63 [95%CI,0.62–0.64],

p=0.004),andlengthofhospitalization>10days(AUROC0.61 [95%CI,0.60–0.63]vs.0.59[95%CI,0.58–0.61],p<0.001).There wasnodifferencebetweenthescoresintermsofthe predict-inglengthofMV>7days.

Table 1shows acomparisonofthe outcomes according to thepresenceor absence oforgan dysfunctionand SIRS. Patients with both organ dysfunction and SIRS had worst outcomescomparedtopatientsofothergroups:higherICU mortality,higherneedofMV,andlongerICUstay.The com-parisonofoutcomesamongpatientswithSIRSbut without organ dysfunctionandpatientswithorgan dysfunctionbut withoutSIRSshowednostatisticaldifference.Patientswith neitherorgandysfunctionnorSIRShadbetteroutcomes:lower ratesofmortalityandMVandshorterlengthofICUstayin comparisontopatientsfromothergroups.

InthisstudyconstitutedofBraziliancriticalcarepatients with suspected infections who were admitted to a mixed medical-surgical ICU, the SOFA ≥2 criteria identified more

patientswithsepsisthantheSIRS≥2criteria.Therewasno

differencebetweenthetwoscoresinpredictingICU mortal-ity;however,SOFA≥2showedamarginallybetterpredictive

accuracyforneedforMV, lengthofICUstay,and lengthof hospitalizationincomparisontotheSIRS≥2definition.The

prognosisofpatientsclassifiedashavingsepsisbySOFA≥2

but notbySIRS≥2(n=308),was generallypoorer than the

prognosisofpatientswithinfectionbutwithoutSIRSororgan dysfunction.Conversely,somepatientspreviouslyclassified ashavingsepsisbySIRS≥2werenotcapturedbytheSOFA≥2

Icu mortality

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1.00 0.00 0.20 0.40 0.60 0.80 1.00 0.00 0.20 0.40 0.60 0.80 1.00

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P = 0.001 P < 0.001

P = 0.001 P = 0.90

P = 0.90

Hospital stay > 10 days

SOFA

+

SIRS +

Need of mv Length of mv > 7 days

1 - Specificity 1 - Specificity

1-Specificity 1-Specificity

1 - Specificity

Sensitivity

Sensitivity

Sensitivity

Sensitivity Sensitivity

Fig.1–ComparisonofpredictiveaccuracyforoutcomesamongSOFAandSIRScriteriadefiningsepsisin1487criticalcare patientswithinfectionatICUadmission.Abbreviations_{:AUROC,areaunderreceiveroperatingcharacteristiccurve;CI,} confidenceinterval;ICU,intensivecareunit;MV,mechanicalventilation.

Note_{:SOFA+,patientswithSOFAvariation}≥2overtheirbaselineclinicalscores.SIRS+,patientswithatleast2ofthe

followingsignsofSIRS:temperature>38◦_Cor<36◦_{C,heartrate>90beatsperminute,respiratoryrate>20breathsper} minuteorPaCO2<32mmHg,abnormalwhitebloodcellcount(>12,000/␮Lor<4000/␮Lor>10%immatureforms).

ICUmortality:SOFA+AUROC0.64(95%CI,0.62–0.67);SIRS+AUROC0.64(95%CI,0.62–0.67).NeedforMV:SOFA+AUROC0.64 (95%CI,0.62–0.65);SIRS+AUROC0.62(95%CI,0.61–0.63).LengthofMV>7days:SOFA+AUROC0.57(95%CI,0.55–0.60); SIRS+AUROC0.58(95%CI,0.56–0.61).ICUstay>7days:SOFA+AUROC0.64(95%CI,0.62–0.65);SIRS+AUROC0.62[95%CI, 0.61–0.63).Hospitalstay>10days:SOFA+AUROC0.61(95%CI,0.60–0.63);SIRS+AUROC0.59(95%

CI,0.58–0.61).

incomparisontopatientswithinfectionbutwithoutSIRSor organdysfunction.

SepsisdefinitionsbasedonSIRScriteriahavebeen ques-tioned due to low specificity.11 _{Critical care patients may} presentsignsofSIRSduetodistinctcausesofinfectionsuch assurgery,trauma,inflammatoryconditions,blood transfu-sions,andmedicationuse.12_{Conversely,immunosuppressed} patientsmaynotmanifestSIRSeveninmoreseverecasesof infectionduetoanimpairedhostresponsetopathogens.13

Inthissense,SOFA≥2criteriaidentifiedahighernumber

ofsepticpatientsincomparisontotheSIRS≥2criteria.This

findingmayberelatedtothecharacteristicsofourpopulation, giventhatweevaluatedmainlyolderpatientswitharelevant comorbidityburden.Particularlyinthispopulation,thesigns ofSIRStendtobelessprevalentduetoweakerimmune sys-temactivation.14_{Thishypothesisissupportedinastudyby} Kaukonenetal.,inwhichuptooneineveryeightpatients

withinfectionandorgandysfunctiondidnotmeettheSIRS criteria.15

Raith et al.16 _{showed that an increase in SOFA score} of 2 or more points had a better prognostic accuracy for in-hospital mortality than SIRS criteria amongadultswith suspectedinfectionadmittedtoAustralianandNewZealand ICUs,suggestingthat SIRScriteriamay havelimited utility for predictingmortalityin the critical caresetting. Similar results were foundin a study byCheng et al.,17 _{in which} Sepsis-3 showed better predictive accuracy for in-hospital mortality than Sepsis-1 amongICU patients in China.The BrazilianstudybyBesenetal.18_{showedthatthenewSepsis-3} definitionsweresuperiortothepreviousdefinitionsin strati-fyingmortalityaswell.Ourstudyfailedtoshowadifference in thepredictive accuracyfor ICUmortality betweenSOFA

≥2criteriaandSIRS≥2criteria;however, thebetter

Table1–ComparisonofoutcomesamongSOFAandSIRScriteriadefiningsepsisin1487criticalcarepatientswith infectionatICUadmission.

Outcomes Group1SIRS+ Group2SIRS+ Group3SIRS− Group3SIRS− Kruskal–Wallisor PearsonChi2

Comparison group

Posthoc p-value SOFA+ SOFA− SOFA+ SOFA−

(n=867) (n=153) (n=308) (n=159)

ICUmortality,%(n) 26.8(233) 16.3(25) 14.2(44) 5.6(9) Chi2_{51.1 1vs.2 0.03}

p<0.001 1vs.3 <0.001 1vs.4 <0.001 2vs.3 0.44 2vs.4 0.01 3vs.4 0.03

NeedforMV,%(n) 68.5(594) 45.7(70) 54.2(167) 20.1(32) Chi2_{144.8 1vs.2 <0.001}

p<0.001 1vs.3 <0.001 1vs.4 <0.001 2vs.3 0.18 2vs.4 <0.001 3vs.4 <0.001

LengthofMV,days, median(IQR)

6(3,13) 6(2,11) 4(1,10) 2(1,7) Chi2_{19.3 1vs.2 0.90}

p<0.001 1vs.3 0.004 1vs.4 0.002 2vs.3 0.22 2vs.4 0.10 3vs.4 0.32

LengthofICUstay, days,median(IQR)

10(5,19) 7(4,15) 7(4,15) 4(2,9) Chi2_{83.5 1vs.2 <0.001}

p<0.001 1vs.3 <0.001 1vs.4 <0.001 2vs.3 0.99 2vs.4 <0.001 3vs.4 <0.001

Lengthof hospitalization, days,median(IQR)

18(10,34) 14(8,29) 16(9,32) 11(7,22) Chi2_{29.9 1vs.2 0.15}

p<0.001 1vs.3 0.62 1vs.4 <0.001 2vs.3 0.68 2vs.4 0.42 3vs.4 <0.001

ICU,intensivecareunit;IQR,interquartilerange;MV,mechanicalventilation;SIRS,systemicinflammatoryresponsesyndrome;SOFA,sequential organfailureassessment.

Note:SOFA+,patientswithSOFAvariation≥2overtheirbaselineclinicalscore.SIRS+,patientswithatleast2ofthefollowingsignsofSIRS:

temperature>38◦_Cor<36◦_{C,heartrate>90beatsperminute,respiratoryrate>20breathsperminuteorPaCO}

2<32mmHg,abnormalwhite

bloodcellcount(>12,000/␮Lor<4000/␮Lor>10%immatureforms).

outcomes(i.e.,needofMV,lengthofICU,andhospitalstay)

indicates that SOFA may bea useful index toassess the

impactoftherapiesonclinicallyand economicallyrelevant outcomesin ICUs.Interestingly,the useofSIRS≥2criteria

identifiedaconsiderablenumberofpatientswithhigh mor-talityrates notclassified as havingsepsis bythe SOFA ≥2

criteria. Also, the use ofSIRS ≥2 in addition to the SOFA

criteriaallowedtheidentificationofasubgroupofpatients

withbothSIRSandorgandysfunction,whichhadtheworst

prognosis.

Somelimitationsmustbeacknowledged.First,a retrospec-tivestudydesignissusceptibletoselectionbias;notablythe useofsearchtermsintheICUdatabaseasastrategyto iden-tifypatientsadmittedduetosuspectedinfectionsmayhave

contributedtoselectionbiasgivenitslowsensitivity.Second, thisstudywasperformedatasinglecenter,whichmaylimit its externalvalidity. Third, wedidnotevaluatethe impact ofthedifferentdefinitionsofsepsisonlong-termoutcomes ofICUpatients.Thestrengthsofourstudyincludethe sub-stantialnumberofpatientsevaluatedandtheassessmentof relevantoutcomesinadditiontomortality.

incriticallyillpatientsinasettingotherthanthoseoriginally published.However,theSIRSscoreisstillimportantin strati-fyingtheseverityofpatientswithinfectionandshouldnotbe abandoned.

Conflicts

of

interest

Theauthorsdeclarenoconflictsofinterest.

Acknowledgement

TheauthorsthanktheICUteamofHospitalMoinhosdeVento whocreatedthedatabase.

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