ADAPTED: Assessment of Disease Severity, Progression and Treatment in Infected Patients Presenting to the Emergency Department

Despite significant improvements in diagnostic and preventative measures, the incidence of sepsis has continued to escalate rapidly in hospitalized patients, with mortality rates ranging between 10 - 54%, depending on the level of severity. The earliest possible identification and assessment of sepsis patients entering the Emergency Department (ED) is therefore crucial in providing the patient with the most appropriate management and treatment strategy at the earliest time point possible. Indeed, an early identification of patients with an infection and at a high risk of cardiovascular and organ dysfunction can lead to an earlier individualised treatment, a potential reduction in the number of clinical complications, and an overall decrease in hospital mortality.

Adrenomedullin (ADM), a 52 amino acid peptide, is a member of the calcitonin peptide family and is widely expressed in many tissues and organs, although its main sources of production include the endothelial and vascular smooth muscle cells. Adrenomedullin can act as both a hormone and cytokine (often termed a "hormokine") in an autocrine and paracrine manner, and its potent vasodilatory and hypotensive response is elicited through an initial increase in cyclic adenosine monophosphate levels, and a subsequent production of nitric oxide.

The importance of adrenomedullin in homeostasis is illustrated by its central role in the up- and down-regulation of cytokines and other mediators, as well as its own stimulatory and inhibitory effect on cytokine production. Indeed, Interleukin (IL)-1β and tumour necrosis factor (TNF) are two of the most potent stimulators for adrenomedullin production and adrenomedullin itself is up-regulated by hypoxia, bacterial products and shear stress, amongst many other factors.

Finally, adrenomedullin has been shown to have a variety of physiological functions, including immune-modulating, direct bactericidal, diuretic and potent vasodilatory activity, and in healthy conditions, circulates at low picomolar concentrations. However, plasma levels are significantly up-regulated in many diseased states in proportion to disease severity such as hypertension, renal failure, lower respiratory diseases and septic shock, due to either damage to the endothelial cells or microvascular and microcirculatory impairment.

This allows clinicians to determine the patients most at risk of developing complications upon their admission to the ED or ICU, in order to rapidly triage and administer the most effective treatment, in the shortest space of time.