Abstract

Background: Plasma secretoneurin (SN) is directly correlated to cardiomyocyte Ca 2+ handling and provides independent prognostic information in cardiovascular disease. Whether SN may predict mortality in patients with severe sepsis or septic shock is not established. Methods: We measured SN levels in serial plasma samples collected on days 1, 2, and 7 in 958 patients enrolled in the multicenter, open-label, randomized, controlled ALBIOS trial, that tested either 20% albumin and crystalloid solutions or crystalloid solutions alone in patients with severe sepsis or septic shock. Endpoints were ICU or 90 day mortality. Results: SN levels on day 1 were higher in non-survivors compared to survivors, both for ICU mortality (235 [Q1-Q3 188-290] vs. 192 [155-246] pmol/L, p<0.0001) and for 90 day mortality (227 [183-283] vs. 188 [154-234] pmol/L, p<0.0001). Admission SN levels were influenced by age and lactate, creatinine and NT-proBNP levels. Stratifying patients according to SN quartiles on day 1 separated survivors and non-survivors during follow-up (Figure). After adjusting for clinical risk factors, SAPS II and SOFA scores, and cardiac biomarkers (hs-cTnT and NT-proBNP), SN levels (logarithmical transformed) on day 1 remained significantly associated with ICU mortality (OR 1.29 [95% CI 1.07-1.55], p=0.007) and 90 day mortality (OR 1.22 [1.02-1.47], p=0.03). SN levels on day 2, but not day 7, were also independently associated with ICU and 90 day mortality. SN levels on day 1 and 2 improved prognostic accuracy for ICU and 90 day mortality as assessed by the category-free net reclassification index. We found no interactions between SN levels and randomization to albumin replacement for prediction of mortality during follow-up. Changes in SN levels over time were not predictive of subsequent mortality. Conclusion: SN provides incremental information to established risk models and cardiovascular biomarkers in patients with severe sepsis and septic shock.

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