The study was approved by the Ethics Committee of the French selleck inhibitor Society of Intensive Care (CE-SRLF 07-185) and informed consent was given by patients’ next of kin.PatientsForty-three patients suffering from septic shock and with at least one additional organ failure were consecutively enrolled. Septic shock was diagnosed according to the criteria given by the Consensus Conference [1]. Measurements were performed as early as possible within the first 24 hours after starting vasopressor therapy (norepinephrine >0.05 ��g/kg/minute). All septic shock patients were enrolled except those in which monitoring StO2 on the thenar eminence was not possible (one patient).

All patients were mechanically ventilated and invasively monitored for hemodynamic parameters with arterial and central venous catheters (Vigilance PreSep CEDV(X3820HS); Edwards Lifesciences, Irvine, CA, USA) or pulmonary artery catheters (Swan Ganz CCOmboV CCO/SvO2/CEDV; Edwards Lifesciences), with continuous measurement of central venous oxygen saturation (ScvO2) or mixed venous oxygen saturation (SvO2), respectively. Cardiac output was also measured, either by the thermodilution technique or by esophageal Doppler (CardioQ ED probe; Deltex, Brighton, UK) [25]. Light sedation and analgesia were provided according to the evaluation of individual needs by the physician in charge (flunitrazepam 1 to 2 mg/hour and fentanyl 50 to 200 ��g/hour, propofol 50 mg/hour, or ketamine 50 to 200 mg/hour). Measurements were performed distant from modifications in the sedation protocol (at least 6 hours) or in the cardiovascular support (at least 1 hour).

Patients were treated according to written intensive care unit standard management for septic shock, very similar to the Surviving Sepsis Campaign [26]. Additional treatments such as recombinant human activated protein C, hydrocortisone or nitric oxide donors were collegially decided. No interventions were based on measured StO2 parameters.For each patient, the following data were collected. Routine laboratory items were measured on the first day of septic shock to calculate the Simplified Acute Physiology Score II [27] and the Sequential Organ Failure Assessment (SOFA) score [28]; repeated for calculation of the SOFA score on days 2 and 3.

Macrohemodynamic parameters measured were the heart rate, blood pressure, cardiac output, right atrial pressure, ScvO2 or SvO2 (catheter measurement) and peripheral oxygen saturation (SpO2) (pulse oximetry Dr?ger SC 9000, adult disposable oximetry sensor Novadiem 3311-V, Nellcor compatible; Dr?gerwerk AG & Co. KGaA, L��beck, Germany). The metabolic parameters Brefeldin_A of arterial and venous blood gases, arterial lactate, and hemoglobin concentration were also collected on days 1, 2 and 3 and were compared with NIRS-derived parameters.