Hypothalamic–pituitary–adrenal (HPA) axis is an important part of the neuroendocrine system that responds to stressors which disrupt the homeostatic balance [14]. AVP is one of the key hormones of the HPA axis, and copeptin, a peptide consisting of 39 amino acids, is released together with AVP during processing of the precursor peptide [15, 16]. In contrast to the biochemically instable AVP, which has a short half-life in blood and is bound to a great extent to platelets, copeptin is a stable protein in the circulation and reliably mirrors biologically functional vasopressin in both healthy and acutely ill patients [17–20].
Of note, the spectrum of diseases underlying non-specific complaints is extremely broad in the ED. When the diagnosis is unclear, risk stratification and early prognostication become challenging correspondingly, but are still of particularly importance. The Basel Non-specific Complaints (BANC) study [21] was a delayed type cross-sectional diagnostic study with a prospective 30-day follow-up showed that sensitive risk stratification tools were needed to identify whether the patients with nonspecific complaints presenting to the ED had potentially adverse health outcomes.
Copeptin is triggered by many diseases, not limited to one single organ system. Its non-specificity, with respect to a precise diagnostic role, is its strength as a more generalized marker for acute critical illness [22]. In a prospective observational single-center study including 225 critically ill patients admitted to a medical ICU [23], non-survivors within 30 days after ICU admittance showed significantly higher circulating copeptin levels as compared to survivors. Circulating levels of copeptin at ICU admission independently predict 30-day mortality in patients admitted to a medical ICU. In our study, we confirmed the value of copeptin as a short-term prognostic biomarker in elderly patients with critical illness. The serum copeptin levels were significantly higher in non-survivors as compared with survivors. Multivariate logistic regression analysis showed that copeptin was an independent risk factor for 30-day mortality in elderly patients with critical illness. Therefore, copeptin may well be a clinically useful non-specific prognostic marker reflecting disease severity and survival.
Back in 2012, the UK Royal College of Physicians developed the National Early Warning Score (NEWS), a simple and easy to use tool at the bedside, which has become a common tool for predicting deterioration in acute critical illness patients [12, 13]. NEWS can be used to standardize the assessment of acute-illness severity not only when acute ill patients present to the hospital or as a surveil-lance system for all patients in hospitals, but potentially also in the pre-hospital assessment [24]. Through its use, clinical staff has a better indication whether a patient is more at risk, which make it possible to timely intervene and stabilize a patient before further deterioration occurs. Thus far the NEWS is the most sensitive Early Warning Score available [25].
A retrospective cohort study by Pirneskoski J et al. [26] including 35800 patients, showed that pre-hospital NEWS score had a good specificity and sensitivity for prediction of death within 1 day of emergency medical services dispatch. Another retrospective observational cohort study [27] with 81,520 consecutive ED patients concluded that the NEWS could predict in-hospital mortality within 24 h, 48 h, 7 days, and 30 days for patients arriving at the ED. In our study, median NEWS points were significantly higher in non-survivors as compared with survivors. Multivariate logistic regression analysis showed that NEWS was independent risk factors for 30-day mortality in elderly patients with critical illness. NEWS showed a good performance for predicting 30-day survival in elderly patients with critical illness, the same with copeptin.
As has been mentioned above, copeptin and NEWS both showed a good performance for predicting 30-day survival in elderly patients with critical illness. However, it was never reported whether copeptin combined with NEWS have a stronger predictive power on the prognosis of elderly patients with critical illness comparting to both factors independently.
From our multivariate logistic regression analysis, copeptin combined with NEWS were also an independent risk factor for 30-day mortality in elderly patients with critical illness. In the further study, we concluded that copeptin combined with NEWS performed a much higher predictive value for 30-day survival using the Z test to compare the areas under the ROC curves. Importantly, we also calculated the optimal cut-off value of copeptin and NEWS using the Youden index. Risk stratification analysis showed that the high-risk group with both higher copeptin levels and higher NEWS points had the highest risk of death. Therefore, our study concluded that copeptin combined with NEWS have a stronger predictive power on the prognosis of elderly patients with critical illness.