Copeptin Predicts Mortality in Critically Ill Patients

Abstract

BackgroundCritically ill patients admitted to a medical intensive care unit exhibit a high mortality rate irrespective of the cause of admission. Besides its role in fluid and electrolyte balance, vasopressin has been described as a stress hormone. Copeptin, the C-terminal portion of provasopressin mirrors vasopressin levels and has been described as a reliable biomarker for the individual’s stress level and was associated with outcome in various disease entities. The aim of this study was to analyze whether circulating levels of copeptin at ICU admission are associated with 30-day mortality.MethodsIn this single-center prospective observational study including 225 consecutive patients admitted to a tertiary medical ICU at a university hospital, blood was taken at ICU admission and copeptin levels were measured using a commercially available automated sandwich immunofluorescent assay.ResultsMedian acute physiology and chronic health evaluation II score was 20 and 30-day mortality was 25%. Median copeptin admission levels were significantly higher in non-survivors as compared with survivors (77.6 IQR 30.7–179.3 pmol/L versus 45.6 IQR 19.6–109.6 pmol/L; p = 0.025). Patients with serum levels of copeptin in the third tertile at admission had a 2.4-fold (95% CI 1.2–4.6; p = 0.01) increased mortality risk as compared to patients in the first tertile. When analyzing patients according to cause of admission, copeptin was only predictive of 30-day mortality in patients admitted due to medical causes as opposed to those admitted after cardiac surgery, as medical patients with levels of copeptin in the highest tertile had a 3.3-fold (95% CI 1.66.8, p = 0.002) risk of dying independent from APACHE II score, primary diagnosis, vasopressor use and need for mechanical ventilation.ConclusionCirculating levels of copeptin at ICU admission independently predict 30-day mortality in patients admitted to a medical ICU.

Clinical relevance of copeptin plasma levels as a biomarker of disease severity and mortality in critically ill patients

“…Nonetheless, the activation of this pathway, as reflected by copeptin, is closely related to the patients’ prognosis at and beyond the ICU. In agreement with prior studies in patients with acute illnesses that noted an association with short‐term mortality, our study confirmed the value of copeptin levels as a prognostic biomarker for the ICU mortality. More strikingly, copeptin plasma concentrations at the admission to the ICU even predicted the long‐term, overall mortality of critically ill patients in our study.…”

“…We conducted a large observational study, in which we prospectively enrolled 218 critically ill patients from our medical ICU, to determine the value of copeptin as a biomarker in the intensive care setting. In line with previous reports of patients with acute illnesses, critically ill patients had significantly higher circulating copeptin levels as compared to healthy controls. However, the disease entity (eg sepsis) or metabolic comorbidities that would affect copeptin levels in the chronic setting did not determine copeptin concentrations in critical illness.…”

“…In line with previous reports of patients with acute illnesses, 6,[10][11][12][13] critically ill patients had significantly higher circulating copeptin levels as compared to healthy controls. However, the disease entity (eg sepsis) or metabolic comorbidities that would affect copeptin levels in the chronic setting 4,9 did not determine copeptin concentrations in critical illness.…”

“…In line with the biological functions of vasopressin, such as water reabsorption, regulating osmolality, vasoconstriction, and central nervous effects, copeptin levels were found elevated in patients with diabetes insipidus, metabolic diseases, chronic kidney diseases, and cardiovascular disorders . In cohorts of patients with acute illnesses, copeptin levels were increased, especially in patients with sepsis, shock, heart failure, and respiratory distress . Some of these studies suggested that elevated copeptin plasma concentrations might indicate an increased short‐term mortality risk .…”

“…4,9,10 In cohorts of patients with acute illnesses, copeptin levels were increased, especially in patients with sepsis, shock, heart failure, and respiratory distress. 6,[10][11][12][13] Some of these studies suggested that elevated copeptin plasma concentrations might indicate an increased short-term mortality risk. 6,[11][12][13] The favourable biochemical properties of copeptin, its implication in pathways of biological stress and the reported association with short-term outcome in acute illness prompted us to investigate plasma copeptin concentrations in a large, prospectively enrolled cohort of critically ill medical patients.…”