Risk assessment of sepsis through measurement of proAVP (copeptin): a secondary analysis of the TRIAGE study

OBJECTIVE: Systemic infections and sepsis lead to strong activation of the vasopressin system, which is pivotal for stimulation of the endocrine stress response and, in addition, has vasoconstrictive and immunomodulatory effects. Our aim was to assess the significance of the vasopressor system through measurement of C-terminal proAVP (copeptin) regarding mortality prediction in a large prospective cohort of patients with systemic infection. DESIGN AND METHODS: This secondary analysis of the observational cohort TRIAGE study included consecutive, adult, medical patients with an initial diagnosis of infection seeking emergency department care. We used multivariable regression analysis to assess associations of copeptin levels in addition to the Sequential Organ Failure Assessment (SOFA) score with 30-day mortality. Discrimination was assessed by calculation of the area under the curve (AUC). RESULTS: Overall, 45 of 609 (7.4%) patients with infection died within 30 days. Non-survivors had a marked upregulation of the vasopressin system with a more than four-fold increase in admission copeptin levels compared to non-survivors (199.9 ± 204.7 vs 46.6 ± 77.2 pmol/L). In a statistical model, copeptin was significantly associated with mortality (adjusted odds ratio of 1.04, 95% CI 1.01 to 1.07, P = 0.002). Regarding discrimination, copeptin alone showed an AUC of 0.82, while adding copeptin to the SOFA score significantly improved its prognostic ability (AUC 0.83 vs 0.86, P = 0.027). CONCLUSION: Activation of the vasopressin system mirrored by an increase in copeptin levels provided significant information regarding mortality risk and improved the SOFA score for prediction of sepsis mortality.