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

Abstract

Objective: Systemic infections and sepsis lead to a 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 4-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 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. Trial registration: ClinicalTrials.gov NCT01768494. Registered January 9, 2013

Surviving Sepsis Campaign Research Priorities 2023

“…Unfortunately, vasopressin measurements are difficult to perform. Copeptin is a stable peptide that is released together with vasopressin (186) and measurement of copeptin reflects endogenous release of vasopressin (186–189). Decreased copeptin levels were associated with hypotension after vasopressin discontinuation (183).…”

Attuali applicazioni della determinazione dei livelli plasmatici di copeptina in contesti non-endocrinologici

“…1). In tale contesto è stato diffusamente dimostrato come i livelli circolanti di copeptina correlino con le condizioni cliniche del paziente e la sua prognosi, predicendone talora la risposta ai trattamenti [12][13][14].…”

“…È infatti assodato come nei pazienti ricoverati in area critica i valori di copeptina aumentino progressivamente da un minimo osservabile in coloro affetti da systemic inflammatory response syndrome (SIRS) in assenza di infezione, verso livelli chiaramente superiori in caso di sepsi o shock settico [12]; contestualmente, livelli del biomarcatore più elevati all'ingresso in Unità di Terapia Intensiva (UTI) si associano a un'aumentata mortalità sia intra-che extra-ospedaliera [13]. Sebbene, quindi, il valore assoluto di copeptina possa di per sé aiutare i clinici nell'identificare i casi più a rischio di outcome negativo, è auspicabile una sua progressiva integrazione ai comuni score prognostici attualmente in uso in UTI.…”