Lactic Acidosis: Current Treatments and Future Directions.
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.
Medical and Research Services VHAGLA Healthcare System, Los Angeles, CA; Division of Nephrology VHAGLA Healthcare System, Los Angeles, CA; UCLA Membrane Biology Laboratory, Los Angeles, CA; David Geffen School of Medicine, Los Angeles, CA. Electronic address: jkraut@ucla.edu.
Jeffrey A
JA
Kraut
Department of Medicine, Division of Nephrology, St. Elizabeth's Medical Center, Boston, MA; Department of Medicine, Tufts University School of Medicine, Boston, MA. Electronic address: nicolaos.madias@steward.org.
Nicolaos E
NE
Madias
D000140:Acidosis, Lactic / Q000188:drug therapy*; D004338:Drug Combinations; D005544:Forecasting; D006801:Humans; D008297:Male; D008875:Middle Aged; D017693:Sodium Bicarbonate / Q000627:therapeutic use
D004338:Drug Combinations; C046283:sodium bicarbonate, sodium carbonate drug combination; D017693:Sodium Bicarbonate
Carbicarb; Lactic acidosis; NHE1; THAM; aerobic glycolysis; base; bicarbonate; dialysis; hypoxia; lactate; metabolic acidosis; sepsis