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.
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].
VASOPRESSORS —
Vasopressors can raise the blood pressure in patients with septic shock but it is unclear if they affect the prognosis.
One report compared the effect of dopamine and epinephrine in 23 patients with lactic acidosis and shock due to sepsis or malaria [17]. Epinephrine had the following deleterious effects:
It raised serum lactate levels (3.2 meq/L versus a fall of 1.0 meq/L with dopamine)
It further lowered the arterial pH (0.05 units versus no change with dopamine)
Why this occurred is not clear. One possibility is that it may worsen tissue hypoxia by causing maldistribution of blood flow.
The American Thoracic Society (ATS) statement on the detection, correction, and prevention of tissue hypoxia, as well as other ATS guidelines, can be accessed through the ATS web site at www.thoracic.org/sections/publications/statements/index.html.
RECOMMENDATIONS —
In summary, the efficacy of and indications for alkali administration in hypoperfusion-induced lactic acidosis remains unresolved [18].
The primary aim of therapy must be reversal of the underlying disease.
At best, raising the extracellular pH will only be of benefit if there is a parallel rise in intracellular pH [15]. This goal does not appear to be achieved with bicarbonate administration during cardiopulmonary resuscitation (CPR) [14,15].
Preliminary studies in patients with shock-induced lactic acidosis have not demonstrated any improvement in cardiac output or systemic blood pressure with the acute administration of sodium bicarbonate (when compared to an infusion of an equivalent amount of sodium chloride) [8].
Because acidemia is only one of many factors affecting the mortality of these critically ill patients, very large numbers will have to be assessed to determine if there is a therapeutic role for alkali.
Partial elevations in both extracellular and intracellular pH can be achieved in patients being ventilated by increasing the rate of ventilation, thereby lowering the PCO2 [15]. Most physicians would limit the use of sodium bicarbonate to patients with severe metabolic acidemia (arterial pH below 7.10 to 7.15), with the aim being to maintain the pH above 7.15 until the primary process can be reversed. There is at present no evidence that alkali therapy is beneficial during CPR [15].
It is possible that the concerns about bicarbonate therapy may not apply to lactic acidosis associated with metformin therapy. In reports of patients with concurrent renal failure, bicarbonate hemodialysis can both correct the acidosis and remove metformin [19,20].