Approach Considerations
Treatment is directed towards correcting the underlying cause of lactic acidosis and optimizing tissue oxygen delivery. The former is addressed by various therapies, including administration of appropriate antibiotics, surgical drainage and debridement of a septic focus, chemotherapy of malignant disorders, discontinuation of causative drugs, and dietary modification in certain types of congenital lactate acidosis.
Cardiovascular collapse secondary to hypovolemia or sepsis should be treated with fluid replacement and vasoactive drugs, with the goal of rapid restoration of cardiac output. Both crystalloids and colloids can restore intravascular volume, but hydroxyethyl starch solutions should be avoided owing to increased mortality. [21] Normal saline (0.9N NaCl) administration can cause a nongap metabolic acidosis due to hyperchloremia, which has been associated with increased acute kidney injury and increases mortality in both non–critically ill and critically ill patients. [32] Balanced salt solutions such as Ringer lactate and Plasma-Lyte will not cause a nongap metabolic acidosis and may reduce the need for renal replacement therapy; however, these can cause a metabolic alkalosis. [33] Step-randomized controlled trials from 2018 have documented an overall 1% increased mortality rate when saline is compared with a balanced salt solution, even if the total amount of fluid administered is less than 2000 mL, with a number needed to treat of 96 patients to save one life. [40, 41] Based on these data, the only indication for 0.9N NaCl infusion should be to treat hypochloremic metabolic alkalosis. If a colloid is indicated, albumin should be used.
Despite appropriate fluid management, vasopressors or inotropes may still be required to augment oxygen delivery. Acidemia decreases the response to catecholamines, and higher doses may be needed. Conversely, high doses may exacerbate ischemia in critical tissue beds. Careful dose titration is needed to maximize benefit and reduce harm.
Lactic acidosis causes a compensatory increase in minute ventilation. Patients may be tachypneic initially, but respiratory muscle fatigue can ensue rapidly and mechanical ventilation may be necessary.
Alkali therapy remains controversial, as no studies have shown improvement in hemodynamic parameters or mortality with its use. Accordingly, no pH has been established after which base should be administered.
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Sodium Bicarbonate
The amount of NaHCO3 required can be calculated by the following formula:
NaHCO3 = (bicarbonate desired - bicarbonate observed) x 0.4 x body weight (kg)
NaHCO3 breaks down into carbon dioxide and water in the tissues. Rapid administration of intravenous NaHCO3 in a patient with circulatory failure can thus lead to intracellular acidosis if the accumulated carbon dioxide cannot be removed from tissues. Additionally, patients must have effective ventilation to eliminate carbon dioxide and should be able to handle additional sodium and volume load.
Because of the potential harms of acidemia, some clinicians still advocate for the use of bicarbonate in severe metabolic acidosis, generally defined as an arterial pH less than 7.15. However, two randomized, controlled trials comparing the effects of bicarbonate versus normal saline on critically ill patients requiring vasopressors demonstrated no improvement in hemodynamics with bicarbonate. [34, 35] It has been proposed that any improvement in hemodynamic status when bicarbonate is administered may be caused by mechanisms other than correction of acidosis (eg, increased preload, effect of tonicity). Thus, the current evidence is strongly against the routine use of intravenous NaHCO3 in the treatment of acquired forms of lactic acidosis.
Tromethamine
Tris-hydroxylmethyl aminomethane (tromethamine [THAM]) is a buffering agent that does not generate carbon dioxide, which confers a theoretical benefit over sodium bicarbonate. It also does not contain sodium, making it an attractive option in critically ill patients with hypernatremia. However, no rigorous studies have compared tromethamine and bicarbonate, so the effect on patient outcome is unclear. It should not be given to patients with renal failure and anuria, as it is renally excreted.
Carbicarb
Carbicarb is a new buffering agent with potential use in metabolic acidosis. It is an equimolecular mixture of sodium bicarbonate and sodium carbonate. Like THAM, Carbicarb has a buffering capacity similar to sodium bicarbonate but does not generate carbon dioxide.
In animal models of hypoxic lactic acidosis, Carbicarb reduced circulating lactate and improved tissue and blood acid-base status compared with sodium bicarbonate.
Carbicarb is currently not available for use.
Hemodialysis
Dialysis may be a useful mode of therapy when severe lactic acidosis exists in conjunction with renal failure or congestive heart failure. Dialysis would allow bicarbonate infusion without precipitating or worsening fluid overload. Therefore, dialysis would correct acidosis by restoring the buffer pool. [36] However, the overall benefit of such therapy for a patient's outcome is not known.
Metformin-induced lactic acidosis has been reported to improve after hemodialysis. Although these data primarily come from case reports, an expert panel recently recommended that extracorporeal removal should be used in severe metformin toxicity. [37]
Other Therapies
A number of other therapies have been advocated at one time or another for lactate acidosis.
The oxidizing agent methylene blue was proposed as a means of pharmacologically altering intracellular redox potential but has proved to be ineffective.
Dichloroacetate is the most potent stimulus of pyruvate dehydrogenase, the rate-limiting enzyme for the aerobic oxidation of glucose, pyruvate, and lactate. Dichloroacetate may inhibit glycolysis and, thereby, lactate production. The data from animal studies and one placebo-controlled, double-blind clinical trial showed dichloroacetate to be superior to placebo in improving the acid-base status of the patients; however, it did not alter hemodynamics or survival.
Theoretical reasons and some clinical evidence exist for thiamine treatment to improve lactic acidosis associated with thiamine deficiency. Thiamine is indicated in patients with beriberi and generally is indicated in patients hospitalized for alcoholism because of their increased tendency for developing thiamine deficiency. Similarly, thiamine can be administered safely to patients with lactic acidosis, particularly in the absence of an obvious alternate etiology. Thiamine is administered intravenously as 50-100 mg followed by 50 mg/d orally for 1-2 weeks.
The treatment for D-lactic acidosis is NaHCO3 to correct acidemia and antibiotics to decrease the number of organisms producing D-lactate.
Therapeutic plasma exchange was reported to successfully treat propofol-infusion syndrome in a single adolescent patient. [38]
Treatment of Critically Ill Patients
Lactic acidosis is observed frequently in patients who are critically ill. Despite a large number of potential etiologies, tissue hyperfusion is by far the most common etiology.
Aggressive cardiorespiratory resuscitation designed to restore tissue perfusion is the fundamental approach to these patients.
Titrating therapies to traditional endpoints (eg, blood pressure) may not ensure that the microvascular bed is reperfused. Monitoring blood lactate concentration not only allows for prognostication but also serves as an indicator of when supportive therapies are restoring tissue perfusion.
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Consultations
Consultation with a critical care medicine specialist for further diagnostic procedures and supportive therapy is recommended for patients who are critically ill.
Patients with chronic, mild hyperlactemia should be referred to an endocrinologist for elucidation of the underlying pathology and appropriate management.
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Pathophysiologic classification of lactic acidosis.
