Rationale and Methodological Approach Underlying the Development of the Sequential Organ Failure Assessment (SOFA)–2 Score

Moreno, R.; Rhodes, A.; Ranzani, O.; Salluh, J.I.F.; Berger-Estilita, J.; Coopersmith, C.M.; Juffermans, N.P.; Laffey, J.; Reinikainen, M.; Neto, A.S.; Tavares, M.; Timsit, J.; Arias Lopez, M.D.P.; Arulkumaran, N.; Azoulay, E.; Chaudhuri, D.; De Lange, D.; De Waele, J.; Dos Santos, C.C.; Bin, D.; Einav, S.; Ferrer, R.; Fujii, T.; Gershengorn, H.B.; Haniffa, R.; Hasan, M.S.; Hollenberg, S.; Ippolito, M.; Jung, C.; Kirov, M.; Lakbar, I.; Lipman, J.; Liu, V.; Lobo, S.M.; Martin, G.S.; Metnitz, P.; Myatra, S.N.; Oczkowski, S.; Paiva, J.; Paruk, F.; Pekkarinen, P.T.; Pilcher, D.; Piquilloud, L.; Pölkki, A.; Prescott, H.C.; Blaser, A.R.; Rezende, E.; Robba, C.; Rochwerg, B.; Schenck, E.J.; Sendagire, C.; Siaw-Frimpong, M.; Simpkin, A.J.; Soares, M.; Summers, C.; Szczeklik, W.; Takala, J.; Vincent, J.; Wendon, J.; Zampieri, F.G.; Shankar-Hari, M.; Singer, M.

doi:10.1001/jamanetworkopen.2025.45040

IMPORTANCE TheSequentialOrganFailureAssessment(SOFA)scorewaspublishedin1996to describeorgandysfunctionincriticallyilladultpatientsinareadilyquantifiableandsequential manner.Considerablechangeshaveoccurredoverthelast3decadesintheuseoforgansupport drugsanddevicesandinpatientoutcomes,necessitatingrevisionofthescore. OBJECTIVES Todevelopdefinitionsoforgandysfunctionthatreflectcurrentunderstandingandto identifyrepresentativevariablestogeneratearevisedSOFAscore(SOFA-2)ofindividualorgan dysfunction. EVIDENCE REVIEW Ataskforceofexpertsinintensivecaremedicineandepidemiologygenerated definitionsoforgandysfunction,identifiedrelevantvariables(physiologicalandlaboratorydata specifictotheorgansystem,pharmacologicalandmechanicalorgansupport),andproposeda0to 4–pointgradingofdysfunctionseveritythroughmeetings,Delphiprocesses,andexplicitrules, informedbydatasynthesis,includingsystematicreviewsandmeta-analysis.Variablesweretestedin 2validationexercisesusingseparatedatasetstotaling3.34millionpatientswithin10representative databasesfromdiversegeographicalandsocioeconomicsettingstoassessdistributionand predictivevalidity(mortalityatintensivecareunitdischarge). Key Points Question Cananupdatetothe SequentialOrganFailureAssessment (SOFA)scorethatreflectscurrent clinicalpracticedemonstratecontent, construct,andpredictivevalidity? Findings Inthisconsensusstatement,a modifiedDelphiprocess,systematic reviews,andanalysisofphysiological, laboratoryandorgansupportdata conductedby60expertsandusingdata from3339470patientsinadult intensivecareunitsin9countries generatedanupdatedSOFAscore (SOFA-2).Thisupdateprovidednew definitions,newvariables,andrevised thresholdstocategorizetheseverityof organdysfunction. Meaning TheSOFA-2scorecaptures contemporaneousclinicalpracticeof organsupportandorgandysfunction– associatedoutcomesinalarge, geographicallyandsocioeconomically diversepopulationofcriticallyilladults receivingcriticalcare. FINDINGS Atotalof60expertsparticipated,with18(30%)femaleparticipants.Overall,65 countrieswererepresented,with33(51%)fromEuropeandCentralAsia,13(20%)fromNorth America;and8(12%)fromLatinAmericaandtheCaribbean.Thephysiologicalvariableswithinthe6 organsystemsusedintheoriginalSOFAscorewereretained,althoughsomecategorieswere renamed(ie,centralnervoussystemwaschangedtobrain,renaltokidney,coagulationto hemostasis,andhepatictoliver).Revisionsoforgansupportdruganddevicevariablesweremadeto reflectcurrentpractice.Alternativevariableswereaddedforinstanceswhenlaboratorydataand/or organsupportinterventionswouldbeinaccessible(eg,insomelow-resourcesettings)ornot indicated(eg,ceilingoftreatment).Somepointcutoffthresholdsweremodifiedbasedonevidence fromsystematicreviewsanddataanalyses.Scorescouldnotbedevelopedfor2additionalorgan systems(gastrointestinalandimmune)duetoinsufficientdata,complexity,orlackofcontentand predictivevalidityforthevariablesassessed.Explicitrulesweredevelopedtofacilitatescoring consistency. CONCLUSIONS AND RELEVANCE Throughamethodologicallyrobustdevelopmentprocess,the SOFA-2scoreoffersupdateddefinitionstodescribeorgandysfunctioninadultpatientsrequiring criticalcareandreadilyquantifiablecriteriatogradethedegreeofdysfunctioninindividualorgan systems.Thisscoreconsiderscontemporaneouschangesinpatientmanagementandoutcomes.

Moreno, R., Rhodes, A., Ranzani, O., Salluh, J.I.F., Berger-Estilita, J., Coopersmith, C.M., et al. (2025). Rationale and Methodological Approach Underlying the Development of the Sequential Organ Failure Assessment (SOFA)–2 Score. JAMA NETWORK OPEN, 8(10) [10.1001/jamanetworkopen.2025.45040].