Lactic Acidosis: Current Treatments and Future Directions

Jeffrey A. Kraut, MD; Nicolaos E. Madias, MD

Disclosures

Am J Kidney Dis. 2016;68(3):473-482. 

In This Article

Abstract and Introduction

Abstract

Mortality rates associated with severe lactic acidosis (blood pH < 7.2) due to sepsis or low-flow states are high. Eliminating the triggering conditions remains the most effective therapy. Although recommended by some, administration of sodium bicarbonate does not improve cardiovascular function or reduce mortality. This failure has been attributed to both reduction in serum calcium concentration and generation of excess carbon dioxide with intracellular acidification. In animal studies, hyperventilation and infusion of calcium during sodium bicarbonate administration improves cardiovascular function, suggesting that this approach could allow expression of the positive aspects of sodium bicarbonate. Other buffers, such as THAM or Carbicarb, or dialysis might also provide base with fewer untoward effects. Examination of these therapies in humans is warranted. The cellular injury associated with lactic acidosis is partly due to activation of NHE1, a cell-membrane Na+/H+ exchanger. In animal studies, selective NHE1 inhibitors improve cardiovascular function, ameliorate lactic acidosis, and reduce mortality, supporting future research into their possible use in humans. Two main mechanisms contribute to lactic acid accumulation in sepsis and low-flow states: tissue hypoxia and epinephrine-induced stimulation of aerobic glycolysis. Targeting these mechanisms could allow for more specific therapy. This Acid-Base and Electrolyte Teaching Case presents a patient with acute lactic acidosis and describes current and future approaches to treatment.

Introduction

Acute lactic acidosis occurring in patients with sepsis or low-flow states is associated with cellular dysfunction and heightened mortality.[1] Elimination or control of the triggering conditions remains the only effective therapy. Often base is prescribed, but its utility remains unproven.[2] Because management of the triggering conditions can be challenging, effective treatment remains elusive.

In this Acid-Base and Electrolyte Teaching Case, a patient with severe sepsis and lactic acidosis is presented. We discuss advances in the pathophysiology of lactic acidosis,[3] thus providing a framework for a future targeted approach to treatment.

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