proadrenomedullin and microcirculation in monitoring organ dysfunction in patient with infection

Conditions: Infection; Sepsis; Septic Shock

Summary: this study evaluates the association between plasmatic levels of mid regional proadrenomedullin (mr-proadm) and the sublingual microcirculation in critical care patients admitted with infection, sepsis or septic shock.

mr-proadm (mid region proadrenomedullin) is a fragment of 48 amino-acids of adm (adrenomedullin), a protein belonging to the super-family of calcitonin-related peptides. mr-proadm is released in a 1:1 ratio with its native protein adm. blood levels of adm are high in several conditions including infection, sepsis of septic shock. mr-proadm seems to be a promising marker for early diagnosis, prognosis and mortality in sepsis and it is also related to sepsis-induced organ failure. the microcirculatory and endothelial damages represent two corner stones of the sepsis pathophysiology. they involved the loss of functional capillaries density and the loss of red blood cells deformability, the endothelial cell disfunction induced by sepsis, the induction of the apoptosis and necrosis, the alteration in the capillary permeability due to the loss of vasomotor tone and control. moreover sepsis is characterised by the increased levels of adhesion molecules and the consequent interaction between neutrophils and endothelium, the fibrin deposition and the activation of the coagulation. the aim of the study is to evaluate the correlation between the alteration in microcirculation and the levels of mr-proadm. mfi (microvascular flow index) is a qualitative measurement of microcirculation and the microcirculatory alterations during sepsis are crucial in the pathophysiology of this syndrome. it is related to prognosis and mortality in patient with sepsis in icu (intensive care unit) studying the relations between mfi and mr-proadm in the first five days of icu stay could represent a good way to connect the pathophysiological background to a laboratory marker for an early diagnosis and for a measure of prognosis in patient with infections. it is also important to compare the levels of mr-proadm with the other microcirculatory parameters (total vessel density, perfused vessels density, percentage of perfused vessels, debacker score, flow heterogeneity index) and with the parameters of glycocalix and endothelial disfunction (perfused boundary region and endothelin-1) when inclusion criteria are present and there are no exclusion criteria, patients will be enrolled for this five-days long study. informed consent will be taken from the patient before enrollment or from the legal representative but when the neurological conditions do not allow at the beginning of the study anthropometric data will be collected together with the main clinical and laboratory parameters (systolic, diastolic and mean arterial pressure, heart rate, mechanical ventilation parameters, blood gas parameters, vasoactive therapy, main parameters for renal, hepatic and haematological function, infectious condition and cultures). arterial blood samples will be collected and blood will be immediately centrifuged and plasma and serum samples will be stored at -80°c for the measurement of mr-proadm and endothelin-1. moreover at the beginning of the study, the day after and the fifth days from the enrolment, the main microcirculatory parameters will be taken through incident dark field technology. glycocheck technology will be used to collect glycocalix conditions.

Eligibility criteria:
inclusion criteria: * suspected infection, infection, sepsis or septic shock in patient admitted in icu from no more than 24 hours and which have previously monitored blood pressure and have a central venous catheter in place. exclusion criteria: * age \< 18 yo * length of stay in icu \> 24 hours; * length of stay in other hospital unit, ward or surgery \> 48 hours; * refusal of informed consent; * conditions that do not allow the possibility of getting a monitoring of sublingual microcirculation (maxillofacial trauma, serious inability to jaw, copious blood loss or secretions from the mouth)

Keywords: sepsis septic shock microcirculation glycocalix proadrenomedullin organ dysfunction critical care intensive care