Abstract
Introduction: Adrenomedullin (ADM) is a free circulating peptide that regulates endothelial barrier function and vascular tone. Here, we sought to study the relationship of adrenomedullin in combination with lactate and the risk of death in patients with out-of-hospital cardiac arrest (OHCA) of non-traumatic origin. Methods: Mid-regional pro-ADM (MR-proADM) concentrations were measured in OHCA patients after successful ROSC on admission. The outcome of interest was all-cause death. Patients were characterized by quartiles (Q) of MR-proADM and lactate concentrations. Cox models were adjusted for age, sex, shockable rhythm, bystander resuscitation, and baseline eGFR. Results: A total of 232 patients were included in the present study (28% women, 67 years, SAPS II score 80). In total, 132 patients (56.9%) died, and 24 patients had an unfavorable neurologic outcome (i.e., a CPC score of 3-4). The median MR-proADM and lactate levels were 1.4 nmol/L (IQR 0.8 to 2.8 nmol/L) and 4.8 mmol/L (IQR 2.8 to 7.4 mmol/L), respectively. MR-proADM concentrations correlated weakly with lactate levels (r=0.23, P<0.001). High (Q4) versus low (Q1-Q3) MR-proADM concentration was associated with an increased rate of death at 28 days (45.4% vs. 75.9%; P<0.001; Fig A ). After multivariable adjustment (including baseline lactate levels), higher MR-proADM levels were significantly associated with an increased risk of death (Q4 vs. Q1-Q3: adjusted HR 1.84, 95% CI 1.21 to 2.77; adjusted HR for 1 unit increase in standardized biomarker 1.55, 95% CI 1.28 to 1.86). The combination of high MR-proADM and high lactate (Q4) concentration identified patients at particularly elevated risk (adjusted HR 3.99; 95% CI 1.67-9.56; Fig B ). Conclusions: Higher MR-proADM concentration are associated with an increased risk of death in patients with OHCA of non-traumatic origin. The combination of high MR-proADM and high lactate levels identifies patients at distinctly elevated risk.
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