Near-infrared spectroscopy (NIRS) is a rapid, Olaparib clinical trial continuous, and non-invasive monitoring system of hemoglobin oxygen saturation in muscle and the brain, and has been used to assess the presence and extent of both circulatory and metabolic disorders in intensive care patients and trauma patients [8,9]. The monitoring system uses near-infrared light (680 to 800 nm) to illuminate tissue, which is mainly absorbed by hemoglobin and myoglobin [10]. Due to the selected wavelength range and the high corresponding spectral absorbance by (de)oxyhemoglobin, the NIRS measurements are confined to vessels with a diameter <500 ��m.Using NIRS, oxyhemoglobin can be distinguished from deoxyhemoglobin because of their differing optical absorption spectra.

The ratio of oxyhemoglobin concentration to deoxyhemoglobin concentration is used to calculate a parameter called tissue oxygen saturation (StO2), describing the oxygenation of the microvasculature in a certain volume of (muscular) tissue. In addition to steady-state StO2 values, NIRS can be used in combination with a vascular occlusion test (VOT), which consists of a baseline phase, an ischemia phase, a reperfusion phase, and a reactive hyperemia phase. Using this methodology in many studies of sepsis, it has been demonstrated in a variety of ways that, following a brief period of ischemia, there is an anomalous tissue reperfusion profile due to disturbed microcirculatory functioning [11,12].

The purpose of the present study was to test the hypothesis that rh-aPC treatment corrects tissue perfusion and microcirculatory reperfusion in septic patients, evaluated with NIRS in combination with a VOT, and to explore whether the NIRS parameters are related to macrohemodynamic indices, metabolic status, and Sequential Organ Failure Assessment (SOFA) score.Materials and methodsPatientsThe study was designed as a prospective observational investigation. For the experimental group (rh-aPC group), we enrolled all patients admitted to the 12-bed polyvalent intensive care unit of the University Hospital of Ospedali Riuniti, Ancona, Italy with a diagnosis of severe sepsis or septic shock – based on the criteria of the International Sepsis Definitions Conference ACCP/SCCM [13] – that could receive rh-aPC treatment (continued infusion of 24 ��g/kg/hour for 96 hours).

We included patients with two or more sepsis-related organ failures (that is, cardiovascular, pulmonary or renal dysfunction, thrombocytopenia, metabolic acidosis with high lactates) or sepsis-correlated Brefeldin_A acute respiratory distress syndrome. Patients with absolute or relative contraindications to rh-aPC therapy were enrolled into the control group. At the onset of severe sepsis or septic shock, the Acute Physiology and Chronic Health Evaluation II score was calculated.All patients were sedated, intubated, and mechanically ventilated.