Sepsis and septic shock increase lactate in a number of exciting ways, many of which have little to do with impaired tissue perfusion (though it does play a role).
Sepsis undeniably results in lactic acidosis and this is not a matter for dispute. However, the origin of the extra lactate is still being disputed. There is no doubt a combination of things happening here.
In summary, the features of sepsis which promote lactic acidosis are as follows:
Thats a confusing diagram, which teaches us nothing about the many sources of lactate in sepsis.
Firstly, the slow circulation is to blame; this results in a delay in the delivery of oxygen to the tissues, as well as a delay in removing the metabolic byproducts, which has the tendency to concentrate the lactate. The evidence for this is strong; the term used to describe this is “microvascular stasis” where collecting post-capillary venules are so vasodilated that flow in them essentially halts. There is at least one excellent article which goes over the potential causes for this stasis, including the increased adhesion of blood cells to endothelia, decreased red cell deformability, microthrombi interfering with the flow, etc. etc.
Another feature of sepsis is that in some tissues the circulatory beds are completely shut down, and there is microcirculatory shunting of oxygenated blood away from these tissues. The net result is decreased oxygen extraction from otherwise well oxygenated blood. This is the patient who has a raised lactate in spite of having a normal (or even elevated) ScVO2.
Then, there is a catecholamine-driven increase in the rate of glycolysis, predominantly in the skeletal muscles, which leads to an excess of pyruvate. This is seen also in people receiving infusions of salbutamol or adrenaline – the mechanism is the same. Conversely, beta-blockade reverses this effect and causes lactate to decrease.
More on that later.
There is also a significant impairment of mitochondrial function, as a result of direct cytokine effects as well as bacterial endotoxin. The main dysfunction seems more to do with the disruption of mitochondrial enzyme complexes responsible for pyruvate metabolism, particularly pyruvate dehydrogenase. The outcome of this is a switch to increased anaerobic metabolism, rather than pyruvate oxidation; and of course the amount of available pyruvate also increases.
Lactate level in sepsis does seem to correlate to the severity of sepsis; and there is some evidence that using lactate as a target of therapy (eg. aiming to decrease it by 20% every 2 hours) improves survival in septic patients. This was a trial where patients received an eight-hour period of aggressive lactate management. Raised lactate was managed by targeting an ScVO2 of 70% or above; if that failed, fluids and vasodilators were commenced (vasodilators to improve microvascular circulation).