The aim of this retrospective cohort study was to identify among the Surviving Sepsis Campaign (SSC) guidelines the optimal bundle of recommendations that minimize 28-day mortality.

The bundle of six recommendations is associated with a dramatic reduction in mortality in sepsis and septic shock. This bundle needs to be evaluated prospectively.

All-cause 28-day mortality was the primary outcome measure. A total of 42,735 patients were included.

Six recommendations (antimicrobials, balanced crystalloid, insulin therapy, corticosteroids, vasopressin, and bicarbonate therapy) were identified from the training cohort to be included in our bundle.

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