The PiCCO device uses pulse contour analysis according to a modified algorithm originally described by Wesseling et al. [15] to determine PCCO and is described in more detail elsewhere [9]. This algorithm enables continuous calculation of stroke volume (SV) by measuring the systolic portion www.selleckchem.com/products/FTY720.html of the aortic pressure waveform and dividing the area under the curve by the aortic compliance. Therefore, the PiCCO device needs to be calibrated by COTCP. Calibrations were regularly performed by an ICU physician at defined time points (0:00 AM, 8:00 AM or 4:00 PM) with the patient in a supine position during a time period without acute hemodynamic instability using three subsequent boluses of 15 mL of ice-cold saline injected into the central venous line as proposed by the manufacturer [9].

During measurement, neither treatment provoking hemodynamic changes nor change of ventilation variables was performed. The dosage of vasopressors was kept constant. Our institutional guideline suggests calibration every 8 hours or before any major change in therapy is initiated. Therefore, additional calibrations by the attending ICU physician were allowed at any time. All hemodynamic data, including PCCO, central venous pressure (CVP), mean arterial blood pressure (MAP), pulse pressure (PP) (systolic minus diastolic aortic pressure) and heart rate (HR) were recorded immediately before and after calibration by COTCP. Global end-diastolic volume index (GEDI) and systemic vascular resistance index (SVRI) were derived upon thermodilution. SV was calculated as COTCP divided by heart rate.

The PP to SV (PP/SV) relationship was used to examine the influence of NE dosage on central arterial stiffness as reported previously [16]. Our ICU is equipped with a patient data management system (PDMS) (CareSuite; Picis Inc., Wakefield, MA, USA) capable of electronically storing hemodynamic variables, including all single thermodilution calibrations, and ventilatory variables minute-by-minute.Statistical analysisStatistical analysis was performed using the statistical software R (R Foundation, Vienna, Austria [17]) and GraphPad Prism 5.01 software (GraphPad Software Inc., San Diego, CA, USA). Data are reported as means �� standard AV-951 deviations (SD) unless otherwise specified. NE subgroups were defined as no NE, low-dose NE (<0.1 ��g/kg/min) and high-dose NE (��0.1 ��g/kg/min) according to the Sepsis-Related Organ Failure Assessment score [18]. Subgroups of time interval elapsed after the latest calibration were defined as <2 hours, 2 to 4 hours, 4 to 8 hours, 8 to 16 hours and 16 to 24 hours. Data subsets for hemodynamic variables, PP/SV ratio and calibration interval were compared using an unpaired two-tailed t-test.