Biochemical indicators of tissue hypoxia and anaerobic metabolism include metabolic acidosis and elevated plasma lactate levels. Hyperlactatemia,in fact,can precede a full in blood pressure in patients who are transitioning from sepsis to severe sepsis, and is therefore an important screening parameter in the febrile normotensive patient. It can result not only from anaerobic metabolism due to hypo-perfusion, but also from direct failure of cellular mitochondrial metabolism, increased glycolysis, and decreased clearance from the liver. In severe sepsis, blood lactate levels are of greater prognostic value than oxygen - derived measures, and a plasma lactate > 4 mmol/L indicates a poor prognosis.