Background: Aggressive fluid resuscitation has become an accepted cornerstone of sepsis management, driven by the belief that hypotension and hyperlactatemia usually arise from inadequate oxygen availability in vital tissues [
5]. However, hyperlactatemia may occur independently of tissue oxygen availability, as indicated by the coexistence of hyperlactatemia and low, normal, or high central venous oxygen saturation (ScvO
2). In the absence of hypoxemia, central venous oxygen desaturation, although an imperfect marker, generally indicates greater than normal O2 extraction elicited by presumed inadequacy of O
2 delivery. Yet, ScvO
2 often remains normal in sepsis, even as metabolic acidosis proceeds. Moreover although the coexistence of hyperlactatemia and low pH is conventionally referred to as “lactic acidosis,” the direct link between excess lactate and acidemia is not straightforward [
6]. In the traditional view, lactate and free protons [lactic acid] are the “abnormal” products of glycolysis in anoxic tissue. Yet, according to the “lactate shuttle theory,” lactate is the “normal” (i.e., expected) end-product of glycolysis, regardless of the oxygen tissue tension, is normally produced without a net release of free protons, and does not directly affect pH [
7]. Thus, although lactate is a useful marker of the severity of shock [
8], well-functioning kidneys regulate the electrolyte balance, compensating for the challenge to ionic balance, and acidemia seldom develops. In the absence of fully compensatory mechanisms, however, any excess of lactate must result in a negative base excess. In septic patients, such compensations may or may not be present, and therefore, there is no direct association between lactate levels and acidemia. Indeed, arterial pH, lactate, and ScvO
2—which according to the traditional interpretative view should be tightly interlinked—are often present in contradictory combinations. Maintenance of normal ScvO
2 suggests that targeting a further boost in oxygen
delivery to peripheral tissues, e.g., by vigorous fluid administration, may be a misdirected response to lactic acidosis—especially when kidney perfusion and function are well preserved.