Mid-regional pro-adrenomedullin and lactate levels for risk stratification in patients with out-of-hospital cardiac arrest

Abstract Background Adrenomedullin 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). Methods Mid-regional pro-ADM (MR-proADM) and lactate concentrations were measured in OHCA patients who survived at least 24 h after return of spontaneous circulation. 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, SAPS II score, and eGFR. Results A total of 232 patients were included in the present study (28% women, 67 years, SAPS II score 80). The median MR-proADM and lactate levels at 24 hours were 1.4 nmol/L (IQR 0.8-2.8 nmol/L) and 1.8 mmol/L (IQR 1.3 to 3.4 mmol/L), respectively. MR-proADM concentrations correlated weakly with lactate levels (r = 0.36, P < 0.001). High (Q4) versus low (Q1-Q3) MR-proADM concentrations were significantly associated with an increased rate of death at 28 days (75.9% vs 45.4%; P < 0.001). After multivariable adjustment (including lactate levels at 24 hours), higher MR-proADM levels were significantly associated with an increased risk of death (Q4 vs. Q1-Q3: adj-HR 1.67, 95%-CI 1.12-2.50; adj-HR for 1 unit increase in standardized biomarker 1.44, 95-CI 1.19-1.73). This relationship remained significant even after further adjustment for baseline NT-proBNP and hsTnT levels. The combination of high MR-proADM and high lactate (Q4) concentration identified patients at particularly elevated risk (adj-HR 3.50; 95% CI 1.92 to 6.39). Conclusions Higher MR-proADM concentrations are associated with an increased risk of death in patients with OHCA, and the combination of high MR-proADM and lactate levels identifies patients at distinctly elevated risk.