TY - JOUR
T1 - Circulating Biologically Active Adrenomedullin (bio-ADM) Predicts Hemodynamic Support Requirement and Mortality During Sepsis
AU - Caironi, P.
AU - Latini, Roberto
AU - Struck, Joachim
AU - Hartmann, Oliver
AU - Bergmann, Andreas
AU - Maggio, Giuseppe
AU - Cavana, Marco
AU - Tognoni, Gianni
AU - Pesenti, Antonio
AU - Gattinoni, Luciano
AU - Masson, S.
AU - Masson, S.
AU - Caironi, P.
AU - Spanuth, E.
PY - 2017/8/1
Y1 - 2017/8/1
N2 - 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 12 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 <.0001, for an increase of 1 interquartile range of bio-ADM concentration). bio-ADM trajectory during the first week of treatment clearly predicted 90-day mortality after adjustment for clinically relevant covariates (hazard ratio [95% CI], 1.3 [1.2-1.4]; P <.0001), and its reduction below 110 pg/mL at day 7 was associated with a marked reduction in 90-day mortality. Changes over the first 7 days of bio-ADM concentrations were not dependent on albumin treatment. 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.
AB - 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 12 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 <.0001, for an increase of 1 interquartile range of bio-ADM concentration). bio-ADM trajectory during the first week of treatment clearly predicted 90-day mortality after adjustment for clinically relevant covariates (hazard ratio [95% CI], 1.3 [1.2-1.4]; P <.0001), and its reduction below 110 pg/mL at day 7 was associated with a marked reduction in 90-day mortality. Changes over the first 7 days of bio-ADM concentrations were not dependent on albumin treatment. 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.
KW - adrenomedullin
KW - biomarker
KW - fluid requirement
KW - prognosis
KW - sepsis
KW - septic shock
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U2 - 10.1016/j.chest.2017.03.035
DO - 10.1016/j.chest.2017.03.035
M3 - Article
AN - SCOPUS:85027492802
VL - 152
SP - 312
EP - 320
JO - Chest
JF - Chest
SN - 0012-3692
IS - 2
ER -