85.As the most discriminating parameter for outcome and severity [22], the determinants of the StO2 reperfusion slope require discussion. The relationship with macrohemo-dynamics is the first line of investigation. We observed a significant relation thenthereby only between cardiac output and the StO2 reperfusion slope, which has never been reported before in septic shock – such a relation had only been shown in severe cardiac failure [42]. Although weak (P < 0.01), the relation indicates that systemic flow influences thenar StO2. Classically in septic shock, adequacy of perfusion for oxygen demand is assessed by the blood lactate level. In the present study, the lactate level logically negatively correlated with the StO2 reperfusion slope, which was slower when lactate levels were higher.

This suggests that NIRS can detect poor tissue oxygenation or bad vascular reserve that results in lactate elevation during septic shock. Taking these relationships (cardiac output and lactate) into account, it is reasonable to think that poor perfusion at the systemic level influences an abnormal StO2 reperfusion slope. Separating the hyperproduction of lactate from a stagnant elevation of lactate level is not possible due to poor washout.The second line of determinants may relate to local perfusion, which may be impaired because of low microvessel blood flow or the low density of perfused microvessels. In addition, changes in vascular blood compartmentalization between venules, capillaries and small arteries may also influence the StO2 measurement.

Despite limitations, initial investigation of these determinants was made measuring forearm skin blood flow using LD at baseline and during the same VOT performed for StO2. In this population of septic shock patients, the LD baseline and the VOT response were abnormal in comparison with healthy volunteers. The abnormal hyperemic response has been attributed to an abnormal capability of the vessels to dilate after ischemia, mediated by a deficit in vasodilatating substances such as prostaglandins or nitric oxide [2,6,9,43]. The nearly significant (P = 0.08) correlation between LD and the StO2 reperfusion slopes is important, since the relation between skin LD and StO2 parameters has not been reported previously. The slower the StO2 slope, the slower the reperfusion slope of the LD.

The combination of a small number of patients and the differences between skin blood flow and skeletal muscle flow regulations may explain the weakness of the correlation [33]. This suggests Drug_discovery a potential impact of microvessel blood flow in the observed abnormal StO2 reperfusion slope.The observed strong correlation between StO2 occlusion and reperfusion slopes needs further discussion; that is, the deeper the occlusion slope, the faster the reperfusion slope.