Development and Validation of the Sequential Organ Failure Assessment (SOFA)-2 Score.

 

Ranzani OT(1)(2)(3), Singer M(4), Salluh JIF(5), Shankar-Hari M(6), Pilcher D(7)(8)(9), Berger-Estilita J(10), Coopersmith CM(11), Juffermans NP(12), Laffey J(13)(14), Reinikainen M(15), Neto AS(7)(16)(17), Tavares M(18)(19), Timsit JF(20)(21), Arias Lopez MDP(22)(23), Arulkumaran N(4), Aryal D(5)(24), Azoulay E(25), Celi LA(26)(27)(28), Chaudhuri D(29)(30), De Lange D(31), De Waele J(32), Dos Santos CC(33)(34), Du B(35)(36), Einav S(37), Engelbrecht T(38), Fazla (39), Ferrer R(40), Finazzi S(41), Fujii T(42), Gershengorn HB(43), Greene JD(44), Haniffa R(45)(46), Hao S(26), Hasan MS(47), Hollenberg S(48), Ippolito M(49), Jung C(50), Kirov M(51), Kobari S(52), Lakbar I(53), Lipman J(54)(55), Liu V(56), Liu X(26), Lobo SM(57), Magatti D(41), Martin GS(58), Metnitz B(59), Metnitz P(60), Myatra SN(61), Oczkowski S(62), Paiva JA(63)(64), Paruk F(65), Pekkarinen PT(66), Piquilloud L(67), Pölkki A(68), Prescott HC(69), Blaser AR(70)(71), Rezende E(72), Robba C(73)(74), Rochwerg B(75), Ruckly S(20)(21), Samei R(41), Schenck EJ(76), Secombe P(7)(77), Sendagire C(5)(78), Siaw-Frimpong M(79), Simpkin AJ(80)(81), Soares M(5), Summers C(82), Szczeklik W(83), Takala J(84), Tanaka S(52), Tricella G(41), Vincent JL(85), Wendon J(86), Zampieri FG(87), Rhodes A(88), Moreno R(89)(90)(91).

 

IMPORTANCE: Acute dysfunction of vital organs is the hallmark of critical illness. The Sequential Organ Failure Assessment (SOFA) score, the most widely adopted approach to describe organ dysfunction, has not been updated in 30 years and therefore may not appropriately capture current clinical practice and outcomes.

OBJECTIVES: To inform the data-driven component of an updated score (SOFA-2) in varied geographical and resource settings (stages 6-8) after expert input via a modified Delphi process (stages 1-5).DESIGN, SETTING, AND PARTICIPANTS: A federated analysis was performed on data collected from adult patients admitted to 1319 intensive care units (ICUs) in 9 countries (Australia, Austria, Brazil, France, Italy, Japan, Nepal, New Zealand, United States) between 2014 and 2023. Four representative multicenter cohorts containing data from 2 098 356 patients were used for data-driven score development and internal validation. External validation was performed on 6 cohorts containing data from 1 241 114 patients.MAIN OUTCOMES AND MEASURES: Content validity for organ dysfunction identified through the modified Delphi process should be reflected by predictive validity using the area under the receiver operating characteristic (AUROC) curve of the score measured on the first ICU day (higher scores indicate worse organ dysfunction).RESULTS: Of 3.34 million patient encounters, 270 108 (8.1%) died in the ICU (range, 4.5% to 20.5% across the 10 cohorts). SOFA-2 modified the 6 organ systems of the original SOFA score (brain, respiratory, cardiovascular, liver, kidney, hemostasis), including new variables and revised thresholds that better describe the organ dysfunction distribution from 0 to 4 points and their associated mortality (SOFA-2 AUROC, 0.79; 95% CI, 0.76-0.81; SOFA-1 AUROC, 0.77; 95% CI, 0.74-0.81). Evaluation of sequential SOFA-2 data from ICU day 1 to day 7 maintained its predictive validity. Insufficient data and lack of content validity precluded incorporation of gastrointestinal and immune dysfunction scores into SOFA-2.

CONCLUSIONS AND RELEVANCE: The SOFA-2 score, updated to include contemporary

organ support treatments and new score thresholds, describes organ dysfunction

in a large, geographically and socioeconomically diverse population of

critically ill adults.

 

DOI: 10.1001/jama.2025.20516

PMCID: PMC12573119

PMID: 41159833 [Indexed for MEDLINE]

 

Outcomerea was the sole franch database involved in the construction of the score. 2 of our members were scientific board members and JFT was resposnble for the Immune component discussion.

 

 

Rationale and Methodological Approach Underlying the Development of the

Sequential Organ Failure Assessment (SOFA)-2 Score: A Consensus Statement.

 

Moreno R(1)(2)(3), Rhodes A(4), Ranzani O(5)(6)(7), Salluh JIF(8),  Berger-Estilita J(9), Coopersmith CM(10), Juffermans NP(11), Laffey J(12)(13),  Reinikainen M(14)(15), Neto AS(16)(17)(18), Tavares M(19)(20), Timsit  JF(21)(22), Arias Lopez MDP(23)(24), Arulkumaran N(25), Azoulay E(26), Chaudhuri  D(27), De Lange D(28), De Waele J(29), Dos Santos CC(30)(31), Du B(32), Einav  S(33), Ferrer R(34), Fujii T(35), Gershengorn HB(36), Haniffa R(37)(38), Hasan  MS(39), Hollenberg S(40), Ippolito M(41), Jung C(42)(43), Kirov M(44), Lakbar  I(45), Lipman J(46)(47), Liu V(48), Lobo SM(49), Martin GS(50), Metnitz P(51),  Myatra SN(52), Oczkowski S(53), Paiva JA(54), Paruk F(55), Pekkarinen PT(56),  Pilcher D(57), Piquilloud L(58), Pölkki A(59), Prescott HC(60)(61), Blaser  AR(62), Rezende E(63), Robba C(64)(65), Rochwerg B(66), Schenck EJ(67),  Sendagire C(68)(69), Siaw-Frimpong M(70), Simpkin AJ(71)(72), Soares M(73),  Summers C(74), Szczeklik W(75), Takala J(76), Vincent JL(77), Wendon J(78), Zampieri FG(79), Shankar-Hari M(80), Singer M(25).

 

 

IMPORTANCE: The Sequential Organ Failure Assessment (SOFA) score was published in 1996 to describe organ dysfunction in critically ill adult patients in a readily quantifiable and sequential manner. Considerable changes have occurred over the last 3 decades in the use of organ support drugs and devices and in patient outcomes, necessitating revision of the score. OBJECTIVES: To develop definitions of organ dysfunction that reflect current understanding and to identify representative variables to generate a revised SOFA score (SOFA-2) of individual organ dysfunction.EVIDENCE REVIEW: A task force of experts in intensive care medicine and epidemiology generated definitions of organ dysfunction, identified relevant variables (physiological and laboratory data specific to the organ system, pharmacological and mechanical organ support), and proposed a 0 to 4-point grading of dysfunction severity through meetings, Delphi processes, and explicit rules, informed by data synthesis, including systematic reviews and meta-analysis. Variables were tested in 2 validation exercises using separate datasets totaling 3.34 million patients within 10 representative databases from diverse geographical and socioeconomic settings to assess distribution and predictive validity (mortality at intensive care unit discharge).FINDINGS: A total of 60 experts participated, with 18 (30%) female participants. Overall, 65 countries were represented, with 33 (51%) from Europe and Central Asia, 13 (20%) from North America; and 8 (12%) from Latin America and the Caribbean. The physiological variables within the 6 organ systems used in the original SOFA score were retained, although some categories were renamed (ie, central nervous system was changed to brain, renal to kidney, coagulation to hemostasis, and hepatic to liver). Revisions of organ support drug and device variables were made to reflect current practice. Alternative variables were added for instances when laboratory data and/or organ support interventions would be inaccessible (eg, in some low-resource settings) or not indicated (eg, ceiling of treatment). Some point cutoff thresholds were modified based on evidence from systematic reviews and data analyses. Scores could not be developed for 2 additional organ systems (gastrointestinal and immune) due to insufficient data, complexity, or lack of content and predictive validity for the variables assessed. Explicit rules were developed to facilitate scoring consistency.

CONCLUSIONS AND RELEVANCE: Through a methodologically robust development process, the SOFA-2 score offers updated definitions to describe organ dysfunction in adult patients requiring critical care and readily quantifiable criteria to grade the degree of dysfunction in individual organ systems. This score considers contemporaneous changes in patient management and outcomes.

 

DOI: 10.1001/jamanetworkopen.2025.45040

PMID: 41159829 [Indexed for MEDLINE]

 

OUTCOMEREA was one of the key database used  mainly for longitudinal analyses..

 

 

Corticosteroids in immunocompromised ICU patients with severe COVID-19: a  multicenter retrospective study.

Dupuis C(1)(2), Timsit JF(3)(4)(5), Domitile J(6), Klouche K(7), Calvet L(6), Neuville M(8), Siami S(9), Cohen Y(10), Laurent V(11), Mourvillier B(12)(13), Goldgran-Toledano D(14), Schwebel C(15), Ruckly S(3)(5), Meziani F(16), Raymond M(17), Dessap AM(18), Souweine B(6)(19).

 

 

Immunocompromised patients were excluded most of the time from trials testing orticosteroids in COVID-19. This study aimed to assess the associations between early corticosteroid use and (1) mortality at day 60, and (2) the occurrence of nosocomial infections in immunocompromised patients with severe COVID-19 admitted to the ICU. It was a multicentre retrospective study, achieved in French ICUs of the Outcomerea™ network and medical ICUs of 4 other hospitals in France. This study included immunocompromised patients admitted to an ICU between January 1, 2020, and August 31, 2022, for severe COVID-19, with an ICU stay of more than 2 days. Patients were classified as receiving early corticosteroid therapy if they were given steroids within the first 5 days following ICU admission. Each patient was categorized into one of four immunosuppression subgroups: 'corticosteroid therapy,' 'monocytic alteration,' 'cellular immunosuppression,' or 'humoral immunosuppression.' Survival analyses were performed, and confounding by indication was addressed using propensity score weighting with overlap. 383 patients were included, 50 were into the o-early-corticosteroids group and 333 in the early-corticosteroids group. In the overlap cohort, 118 were included (46 in the non-early-corticosteroids and 72 in the early-corticosteroids group). There was no association with day-60 mortality (IPTWoverlapHR = 0.97, 95% CI [0.51; 1.85], p = 0.92). There was also no association with the occurrence of nosocomial infections (IPTWoverlapSubHR = 2.59, CI 95% [0.77; 8.7], p = 0.13). We report that steroids had no benefit on mortality in immunocompromised patients admitted to ICU for severe COVID-19.

 

DOI: 10.1038/s41598-025-10864-8

PMCID: PMC12297506

PMID: 40715278 [Indexed for MEDLINE]

 

 

Self-extubation in critically ill patients: from the French OUTCOMEREA Network.

Trenchat L(1), Galerneau LM(2)(3), Ruckly S(4), Sigaud F(1), Terzi N(5), Garrouste M(6), Oziel J(7), Hong Tuan Ha V(8), Gainnier M(9), Siami S(10), Dartevel A(1), Dupuis C(11), Forel JM(12), Dessajan J(13), Adrie C(14), Goldgran-Toledano D(15), Laurent V(16), Argaud L(17), Reignier J(18), Dumas G(1)(19), Darmon M(20), Timsit JF(13); OUTCOMEREA Network.

 

BACKGROUND: Self-extubation is a common complication in intubated patients in the intensive care unit (ICU) and is associated with a high rate of reintubation. This study aimed to identify predictors of reintubation following self-extubation (SE) and assess the prognosis of these patients.

METHODS: Data were extracted from the French ICU database, OutcomeRea™. The primary objective was to identify factors associated with reintubation within 48 h after self-extubation. Secondary objectives included evaluating the association between reintubation and mortality, ICU length of stay, and nosocomial pneumonia.

RESULTS: Between November 1996 and May 2022, 12,917 patients were intubated in the ICU. Among them, 701 patients experienced SE without therapeutic limitations at the time, and 276 (39.4%) required reintubation. In adjusted analyses, the following factors were independently associated with reintubation: a higher non-neurological SOFA score on the day before SE (OR 1.16 [1.01; 1.34]; p = 0.03), duration of invasive mechanical ventilation > 7 days before SE (OR 1.79 [1.04; 3.26]; p = 0.04), enteral nutrition on the day of SE (OR 2.59 [1.75; 3.84]; p < 0.01) and the use of non-invasive ventilation (NIV) within 24 h after SE (OR 0.28 [0.16; 0.5];p < 0.01). Reintubation within 48 h after SE was independently associated with increased 28-day mortality (HR = 3.03 [1.79; 5.12]; p < 0.01) and 90-day mortality (HR = 2.86 [1.86; 4.4]; p < 0.01), a higher risk of nosocomial pneumonia (sdHR, 18.28 [7.70; 43.42]; p < 0.01), and a 13-day increase in ICU length of stay (p < 0.01).

CONCLUSION: Enteral nutrition on the day of SE, prolonged mechanical ventilation prior to SE, higher non-neurological SOFA scores, and use of NIV after SE were independently associated with the need for reintubation. Reintubation was also associated with increased mortality, a higher risk of nosocomial pneumonia, and prolonged ICU stay.

DOI: 10.1186/s13054-025-05472-x PMCID: PMC12235797

PMID: 40624565 [Indexed for MEDLINE]

 

 

Shortening antibiotic therapy duration for hospital-acquired bloodstream infections in critically ill patients: a causal inference model from the international EUROBACT-2 database.

 

Gajdos L(1)(2), Buetti N(2)(3), Tabah A(4)(5)(6), Ruckly S(1)(2), Akova M(7), Sjöval F(8)(9), Arvaniti K(10), de Waele J(11)(12), Bracht H(13), Barbier F(14), Timsit JF(15)(16)(17); EUROBACT-2 Study Group, the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology, the Infectious Diseases (ESCMID) Study Group for Infections in Critically Ill Patients (ESGCIP) and the OUTCOMEREA Network.

Erratum in

    Intensive Care Med. 2025 Oct;51(10):1968-1970. doi:

10.1007/s00134-025-08071-0.

 

INTRODUCTION: Hospital-acquired bloodstream infections (HA-BSIs) are severe and require antibiotic therapy. In non-complicated BSIs, shortened therapy reduces side effects without compromising efficacy. The impact of shortened antibiotic therapy in HA-BSI critically ill patients without indication of prolonged therapy requires further evaluation.

METHODS: Using the international prospective EUROBACT-2 cohort, we compared shortened (7-10 days) versus long (14-21 days) treatment durations in ICU patients eligible for shortened therapy. Patients without antibiotic therapy within 3 days after HA-BSI occurrence or requiring prolonged therapy (due to infection source, microorganism, or clinical deterioration) were excluded. Treatment failure, defined as death, persistent infection, or subsequent infectious complications by Day 28, was assessed using an inverse-probability of treatment weighted (IPTW) logistic regression.RESULTS: Among 2600 patients, 550 were eligible for shortened treatment, 213 received short, and 337 received long treatment. The most common infection source was intravascular catheters (33%), most common microorganisms were Enterobacterales (39%). Patients with long treatment were more frequently infected with Staphylococcus aureus (11% vs. 5.6%, p = 0.025) or difficult-to-treat microorganisms (23% vs. 7%, p < 0.001), and received more commonly combination therapy (46% vs. 30%, p < 0.001). Short treatment was associated with reduced 28-day treatment failure (OR 0.64, 95% CI 0.44-0.93, p = 0.019), mainly due to reduction in subsequent infectious complications (OR 0.58, 95% CI 0.37-0.91, p = 0.018). Mortality (OR 0.92 [95% CI 0.59, 1.43], p = 0.7) and persistent infection rates (OR 0.47 [95% CI 0.17, 1.14], p = 0.12) were similar.

CONCLUSIONS: In selected ICU patients with HA-BSI, shortened antibiotic treatment might be considered. Eurobact2 was a prospective international cohort study, registered in ClinicalTrials.org (NCT03937245).

DOI: 10.1007/s00134-025-07857-6

PMID: 40192823 [Indexed for MEDLINE]

 

 

Risk Factors for Mortality Among Older Adults with Hospital-Acquired Bloodstream

Infections in the Intensive Care Unit: A Multicenter Cohort Study.

 

Hoffman T(#)(1)(2), Margalit I(#)(3)(4), Tabah A(5)(6)(7), Ruckly S(8)(9), Barbier F(10), Singer P(2)(11), Timsit JF(12)(13), Prendki V(14)(15)(16), Hassoun-Kheir N(16), Buetti N(16)(17)(18), Yahav D(1)(2); EUROBACT-2 Study Group, the European Society of Intensive Care Medicine (ESICM), the European Society of Clinical Microbiology, Infectious Diseases (ESCMID) Study Groups for infections in Critically Ill Patients (ESGCIP), Infections in the Elderly (ESGIE), the OUTCOMEREA Network.

 

INTRODUCTION: We aimed to investigate risk factors for mortality among older adults (≥ 75 years) with hospital-acquired bloodstream infections (HA-BSI) in the intensive care unit (ICU).METHODS: We included patients aged ≥ 75 years with HA-BSI in ICU from the EUROBACT-2 cohort (2019-2021). Univariable and multivariable analyses were conducted to identify predictors of 28-day mortality.RESULTS: The cohort included 563 patients (median age 80, 39% women). Mortality at 28 day was 50%. Factors associated with mortality in multivariate analysis were admission due to COVID-19, failure to achieve source control, and higher SOFA. Among older adults with Gram-negative BSI, corticosteroid administration for septic shock was an additional factor. Among functionally independent patients, age itself was not associated with mortality.CONCLUSIONS: HA-BSI in older adults in ICU are associated with high mortality. Inadequate source control is a significant modifiable risk factor. The use of corticosteroids in ICU management of older adults should be further

investigated.

DOI: 10.1007/s40121-024-01104-z PMCID: PMC11829854

PMID: 39794673

 

Early systemic insults following severe sepsis-associated encephalopathy of critically ill patients: association with mortality and awakening-an analysis of the OUTCOMEREA database

Michael Thy ^{#  1   2   3} , Romain Sonneville ^{#  4   5} , Stéphane Ruckly  ^{5   6} , Bruno Mourvillier  ⁷ , Carole Schwebel  ⁸ , Yves Cohen  ⁹ , Maité Garrouste-Orgeas  ¹⁰ , Shidasp Siami  ¹¹ , Cédric Bruel  ¹² , Jean Reignier  ¹³ , Elie Azoulay  ¹⁴ , Laurent Argaud  ¹⁵ , Dany Goldgran-Toledano  ¹⁶ , Virginie Laurent  ¹⁷ , Claire Dupuis  ¹⁸ , Julien Poujade  ⁴ , Lila Bouadma  ^{4   5} , Etienne de Montmollin  ^{4   5} , Jean-François Timsit  ^{4   5} ; on the behalf of the OUTCOME R. E. A. network

• PMID: 39810227
• PMCID: PMC11730477
• DOI: 10.1186/s40560-024-00773-9