A Continuous Metric to Measure Endotype and Corticosteroid Interaction in Septic Shock

Abstract The benefit of corticosteroids for septic shock remains unclear, reflecting heterogeneity of treatment effect. We previously reported a binary septic shock endotype classification based on expression of 100 genes. This binary classification provides information regarding prognosis and corticosteroid responsiveness but does not capture the endotypes continuum. Here, we describe a continuous metric for endotype assignment, the Z value, and its relationship with septic shock outcomes and corticosteroid responsiveness. In a derivation cohort, a lower Z value was independently associated with increased odds of mortality. When the Z value was fit using cubic splines, the odds of mortality increased considerably below a Z value of 15 among patients exposed to corticosteroids. A similar interaction between Z value and corticosteroid exposure was observed when the model was applied to pediatric and adult validation cohorts. The Z value provides more detailed evidence of patients with septic shock in whom corticosteroids are harmful.