The early change of SOFA score as a prognostic marker of 28-day sepsis mortality: analysis through a derivation and a validation cohort

Abstract

Background: Since the Sepsis-3 criteria, change in Sequential Organ Failure Assessment (SOFA) score has become a key component of sepsis identification. Thus, it could be argued that reversal of this change (ΔSOFA) may reflect sepsis response and could be used as measure of efficacy in interventional trials. We aimed to assess the predictive performance of ΔSOFA for 28-day mortality.

Methods: Data from two previously published randomized controlled trials were studied: the first reporting on patients with severe Gram-negative infections as a derivation cohort and the second reporting on patients with ventilator-associated pneumonia as a validation cohort. Only patients with sepsis according to the Sepsis-3 definition were included in this analysis. SOFA scores were calculated on days 1, 2, 3, 5, 7, 14, and 28.

Results: We included 448 patients within the derivation cohort and 199 within the validation cohort. Mean SOFA scores on day 1 were 6.06 ± 4.07 and 7.84 ± 3.39, and 28 day mortality 22.8% and 29.6%, respectively. In the derivation cohort, the earliest time point where ΔSOFA score predicted mortality was day 7 (AUROC (95% CI) 0.84 (0.80-0.89); p < 0.001). The best tradeoff for prediction was found with 25% changes (78% sensitivity, 80% specificity); less than 25% decrease of admission SOFA was associated with increased mortality (odds ratio for death 14.87). This finding was confirmed in the validation cohort.

Conclusions: ΔSOFA on day 7 is a useful early prognostic marker of 28-day mortality and could serve as an endpoint in future sepsis trials alongside mortality.

Trial registration: ClinicalTrials.gov numbers NCT01223690 and NCT00297674.

Keywords: Delta change; Mortality; Sepsis; Sequential Organ Failure Assessment (SOFA); Trial endpoints.

Conflict of interest statement

E Karakike is funded by the Horizon 2020 Marie Skłodowska-Curie Grant European Sepsis Academy (grant 676129 paid to the University of Athens).

EJ Giamarellos-Bourboulis has received honoraria (paid to the University of Athens) from AbbVie USA, Abbott CH, Biotest Germany, Brahms GmbH, InflaRx GmbH, the Medicines Company, MSD Greece, and XBiotech Inc. He has received independent educational grants from AbbVie, Abbott, Astellas Pharma, AxisShield, bioMérieux Inc., InflaRx GmbH, the Medicines Company, and XBiotech Inc. He has received funding from the FrameWork 7 program HemoSpec and from the Horizon 2020 Marie-Curie project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), outside the submitted work.

The other authors declare that they have no competing interests.

Figures

Fig. 1

Flow chart. VAP, ventilator-associated pneumonia; SIRS, systemic inflammatory response syndrome; SOFA, sequential Organ Failure Assessment

Fig. 2

ΔSOFA on follow-up days as predictor of 28-day mortality in the derivation cohort. a Receiver operating characteristic (ROC) curves for the association of change from initial SOFA (ΔSOFA) with 28-day mortality. b Comparisons of AUROCs of ΔSOFA of follow-up days to ΔSOFA of day 2. p values of the indicated comparisons are provided. c Median ΔSOFA scores on follow-up days in survivors and non-survivors. Statistically significant differences at the level of p < 0.0001 were found between survivors and non-survivors at all studied time points. AUROC, area under the ROC; CI, confidence interval