Circulating biologically active adrenomedullin (bio-ADM) predicts hemodynamic support requirement and mortality during sepsis.

Background The biological role of adrenomedullin (ADM), a hormone involved in hemodynamic homeostasis, is controversial in sepsis because administration of either the peptide or an antibody against it may be beneficial. Methods Plasma biologically active ADM (bio-ADM) was assessed on days 1, 2, and 7 after randomization of 956 patients with sepsis or septic shock to albumin or crystalloids for fluid resuscitation in the multicenter Albumin Italian Outcome Sepsis trial. We tested the association of bio-ADM and its time-dependent variation with fluid therapy, vasopressor administration, organ failures, and mortality. Results Plasma bio-ADM on day 1 (median [Q1-Q3], 110 [59-198] pg/mL) was higher in patients with septic shock, associated with 90-day mortality, multiple organ failures and the average extent of hemodynamic support therapy (fluids and vasopressors), and serum lactate time course over the first week. Moreover, it predicted incident cardiovascular dysfunction in patients without shock at enrollment (OR [95% CI], 1.9 [1.4-2.5]; P P Conclusions In patients with sepsis, the circulating, biologically active form of ADM may help individualizing hemodynamic support therapy, while avoiding harmful effects. Its possible pathophysiologic role makes bio-ADM a potential candidate for future targeted therapies. Trial Registry ClinicalTrials.gov; No.: NCT00707122.