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Adrenomedullin has previously demonstrated potential for prognostic enrichment. This study aimed to assess associations of bioactive adrenomedullin (bio-ADM) levels at ICU admission and sepsis outcomes and to evaluate the potential of bio-ADM as marker to identify subgroups of patients with moderate disease severity that might benefit from hydrocortisone treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used data from the HYPRESS trial (NCT00670254) to investigate, if bio-ADM is useful to predict sepsis outcomes (septic shock, 90- and 180-day mortality) and benefit or harm by hydrocortisone treatment. Optimal cut-offs for outcome predictions were determined by Youden\u2019s index. Logistic regression was used to assess bio-ADM subgroups and treatment interaction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Bio-ADM levels differed significantly in patients with or without septic shock within 14 days (p\u2009=\u20090.011). While the area under the ROC curve (AUC) was only 0.603 (CI 0.531\u20130.676), patient subgrouping using bio-ADM levels showed significantly higher cumulative incidence of septic shock within 14 days in the subgroup of patients with bio-ADM levels\u2009\u2265\u200937 pg\/mL (p\u2009&lt;\u20090.001). The odds ratio for the development of septic shock in this group was 4.67 (95% CI 1.53, 20.3, p\u2009=\u20090.016). A bio-ADM cut-off of\u2009\u2265\u2009136 pg\/mL was predictive for 90-day (OR 8.21, 95% CI 2.46\u201327.9, p\u2009&lt;\u20090.001) and 180-day mortality (OR 4.87, 95% CI 1.49\u201316.0, p\u2009=\u20090.008). Hydrocortisone therapy did not reduce the incidence of septic shock (OR 1.59, 95% CI 0.37\u20138.15, p\u2009=\u20090.54), 90-day (OR 1.53, p\u2009=\u20090.23) or 180-day mortality (OR 1.41, p\u2009=\u20090.25), regardless of bio-ADM stratification (interaction term p\u2009=\u20090.58 for septic shock; p\u2009=\u20090.31 for 90-day mortality; p\u2009=\u20090.51 for 180-day mortality).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Whereas bio-ADM levels are associated with sepsis outcomes, our data do not indicate usefulness of the marker to identify patients potentially benefitting from hydrocortisone therapy.<\/jats:p>\n                  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