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There are no reliable, non-invasive methods to accurately measure cardiac output (CO) in septic patients. MostCare (Vytech Health™, Vygon, Padova, Italy), is a beat-to-beat, self calibrated method for CO measurement based on continuous analysis of reflected arterial pressure waveforms. We enrolled 40 patients that were suffering from septic shock and requiring norepinephrine infusion to target blood pressure in order to to evaluate the level of agreement between a calibrated transpulmonary thermodilution device (PiCCO System, Pulsion Medical Systems, Feldkirchen, Germany) and the MostCare system in detecting and tracking changes in CO measurements related to norepinephrine reduction in septic shock patients,. PiCCO was connected to a 5 Fr femoral artery catheter and to a central venous catheter. System calibration was performed with 15 mL of cold saline injection over about 3 s. The MostCare device was connected to the artery catheter to analyze the arterial waveform. Before reducing norepinephrine infusion, the PiCCO system was calibrated, the MostCare waveform was optimized, and the values of the complete hemodynamic profile were recorded (T1). Norepinephrine infusion was then reduced by 0.03 mcg/Kg/min. After 30 min, a new calibration of PiCCO system and a new record on both monitors were performed (T2). Static measurements agreements were assessed using the Bland-Altman test, while trending ability was investigated using polar plot analysis. If volume expansion occurred, then related data were separately analyzed. At T1 mean the CO was 5.38 (SD 0.60) L/min, the mean difference was 0.176 L/min, the limits of agreement (LoA) was +1.39 and −1.04 L/min, and the percentage error (PE) was 22.6%; at T2 the mean CO was 5.44 (SD 0.73) L/min, the mean difference was 0.053 L/min, the LoA was +1.51 and −1.40, and the PE was 27%. After considering the volume expansion between T1 and T2, the mean CO at T1 was 5.39 L/min (SD 0.47), the LoA was +1.09 and −0.78 L/min, and the percentage error (PE) was 17%; at T2 the mean CO was 5.35 L/min (SD 0.81), the LoA was +1.73 and −1.52 L/min, and the PE was 30%. The polar plot diagram seems to confirm the trending ability of MostCare system versus the reference method. In septic patients, when the arterial waveform is accurate, MostCare and PiCCO transpulmonary thermodilution exhibit good agreement even after the reduction of norepinephrine and changes in vascular tone or volume expansion. MostCare could be a rapid to set, reliable, and useful tool to monitor hemodynamic variations in septic patients in emergency contexts where thermodilution methods or other advanced systems are not easily available. [ABSTRACT FROM AUTHOR]