Bicarbonate therapy in lactic acidosis

INTRODUCTION

Like ketoacidosis, lactic acidosis replaces bicarbonate with an organic anion. Removing the stimulus to lactic acid production by treating the underlying disease enables oxidative processes to metabolize the accumulated lactate, resulting in the regeneration of bicarbonate and correction of the acidosis. Thus, treatment with sodium bicarbonate is indicated only for acute control of the acidemia. It has been suggested, for example, that severe acidemia may contribute to continued tissue hypoperfusion by decreasing cardiac contractility via a reduction in myocardial cell pH [1,2]. To the degree that this occurs, the administration of sodium bicarbonate may raise the extracellular pH both directly and by improving oxygen delivery to the tissues.

EFFECTS OF BICARBONATE THERAPY

The infusion of sodium bicarbonate, however, can lead to a variety of problems in patients with lactic acidosis, including fluid overload, a postrecovery metabolic alkalosis (as the excess lactate is converted back to bicarbonate), and hypernatremia. Furthermore, studies in both animals and humans suggest that alkali therapy may only transiently raise the plasma bicarbonate concentration [3,4]. This finding appears to be related in part to the carbon dioxide generated as the administered bicarbonate buffers excess hydrogen ions. This carbon dioxide is normally eliminated via the lungs. However, patients with severe circulatory failure or cardiac arrest often have a marked reduction in pulmonary blood flow. As a result, the newly formed carbon dioxide accumulates in the venous system [5,6]. Mixed venous PCO2 will continue to rise until the product of the greater than normal mixed venous PCO2 and the less than normal pulmonary blood flow is sufficient to eliminate the CO2 that is produced. (See "Arterial and mixed venous blood gases in lactic acidosis".)

It has been proposed that the rise in PCO2 in the venous blood that is perfusing the tissues may then exacerbate the intracellular acidosis, leading to an impairment in both hepatic lactate utilization and cardiac contractility [3,7]. However, careful biochemical analysis suggests that a further reduction in intracellular pH with bicarbonate administration should not occur. Conversion of bicarbonate to CO2 requires that each meq of bicarbonate combine with a meq of proton. The amount of protons carried by blood buffers (proteins, phosphate, hemoglobin) is insufficient to buffer all of the exogenous bicarbonate. Thus, the induced rise in venous CO2 (and fall in venous pH) must be secondary to buffering by intracellular buffers, a process that restores the intracellular pH and the chemical structure of intracellular proteins.

The administration of bicarbonate can also prevent an improvement in cardiac function by inducing a fall in the plasma ionized (unbound) calcium concentration due to increased protein binding [8], since calcium is required for normal cardiac contractility [9]. Cautious administration of calcium may become necessary in some patients.

It is at present unclear if the disparity in mixed venous and arterial PCO2 and pH occurs in septic shock in which the cardiac output is typically above normal but still too low to meet tissue needs. There is, however, no evidence that sodium bicarbonate improves circulatory hemodynamics in this setting [8].