Informed consent was obtained from the patients’ next of kin. Enrolment of patients started in January 2008 and ended in April 2009. We enrolled patients who fulfilled the criteria of septic shock that required norepinephrine (NE) to maintain a mean arterial pressure (MAP) of at least selleck chemical 65 mm Hg despite appropriate volume resuscitation (pulmonary arterial occlusion pressure [PAOP] = 12 to 18 mm Hg and central venous pressure [CVP] = 8 to 12 mm Hg) [18]. Exclusion criteria of the study were age of less than 18 years, pregnancy, significant valvular heart disease, present or suspected acute coronary syndrome, and limitations to the use of inotropes (that is, ventricular outflow tract obstruction and mitral valve systolic anterior motion).

All patients were sedated with sufentanil and midazolam and received mechanical ventilation using a volume-controlled mode.Hemodynamics, global oxygen transport, and acid-base balanceSystemic hemodynamic monitoring of the patients included a pulmonary artery catheter (7.5-F; Edwards Lifesciences, Irvine, CA, USA) and a radial artery catheter. MAP, right atrial pressure, mean pulmonary arterial pressure, and PAOP were measured at end-expiration. Heart rate was analyzed from a continuous recording of electrocardiogram with ST segments monitored. Cardiac index (CI) was measured using the continuous thermodilution technique (Vigilance II; Edwards Lifesciences). Systemic vascular resistance index, pulmonary vascular resistance index, and left and right ventricular stroke work indices were calculated by means of standard equations.

Arterial and mixed-venous blood samples were withdrawn to determine oxygen tensions and saturations as well as carbon dioxide tensions, standard bicarbonate, base excess, pH, and lactate concentrations. SvO2 was measured discontinuously by intermittent mixed-venous blood gas analyses (Gem 4000 Premier; Instrumentation Laboratory Company, Bedford, MA, USA). Systemic oxygen delivery index (DO2I), oxygen consumption index, and oxygen extraction ratio were calculated by means of standard formulae.Microvascular networkMicrovascular blood flow was visualized by means of an SDF imaging device (MicroScan?; MicroVision Medical, Amsterdam, The Netherlands) with a 5�� magnification lens [17]. The optical probe was applied to the sublingual mucosa after gentle removal of saliva with a gauze swab.

Three discrete fields were captured with precaution to minimize motion artifacts. Individual sequences of approximately 15 seconds were analyzed off-line with the aid of dedicated software (Automated Vascular Analysis 3.0; Academic Medical Center, University of Amsterdam, The Netherlands) in a randomized fashion by a single investigator who was unaware of the study protocol. Vessel density was automatically calculated from the software as the total vessel lengths of the small, medium, and large vessels, divided by Drug_discovery the total area of the image [17].