Lactic Acidosis

Published - Written by Carla Rothaus

When lactic acidosis accompanies low-flow states or sepsis, mortality rates increase sharply. A new review summarizes our current understanding of the pathophysiological aspects of lactic acidosis, as well as the approaches to its diagnosis and management.

Lactic acidosis results from the accumulation of lactate and protons in the body fluids and is often associated with poor clinical outcomes. The effect of lactic acidosis is governed by its severity and the clinical context. Mortality is increased by a factor of nearly three when lactic acidosis accompanies low-flow states or sepsis, and the higher the lactate level, the worse the outcome.

Clinical Pearls

What causes lactic acidosis?

Hyperlactatemia occurs when lactate production exceeds lactate consumption. In tissue hypoxia, whether global or localized, lactate is overproduced and underutilized as a result of impaired mitochondrial oxidation. Even if systemic oxygen delivery is not low enough to cause generalized hypoxia, microcirculatory dysfunction can cause regional tissue hypoxia and hyperlactatemia. Hyperlactatemia can also result from aerobic glycolysis, a term denoting stimulated glycolysis that depends on factors other than tissue hypoxia.  Activated in response to stress, aerobic glycolysis is an effective, albeit inefficient, mechanism for rapid generation of ATP. In the hyperdynamic stage of sepsis, epinephrine-dependent stimulation of the (beta)2-adrenoceptor augments the glycolytic flux both directly and through enhancement of the sarcolemmal Na+,K+-ATPase (which consumes large quantities of ATP). Other disorders associated with elevated epinephrine levels, such as severe asthma (especially with overuse of beta2-adrenergic agonists), extensive trauma, cardiogenic or hemorrhagic shock, and pheochromocytoma, can cause hyperlactatemia through this mechanism. Drugs that impair oxidative phosphorylation, such as antiretroviral agents and propofol, can augment lactic acid production and on rare occasions cause severe lactic acidosis. Cardiogenic or hypovolemic shock, severe heart failure, severe trauma, and sepsis are the most common causes of lactic acidosis, accounting for the vast majority of cases.

Table 1. Causes of Lactic Acidosis.

How is lactic acidosis diagnosed?

An elevated serum anion gap, particularly a value higher than 30 mmol per liter, can provide supportive evidence. However, other causes of a raised anion gap, such as ketoacidosis and toxic alcohol ingestion, should always be considered. A normal anion gap does not rule out lactic acidosis. In one study, 50% of patients with a serum lactate level of 5 to 10 mmol per liter did not have an elevated anion gap. Correction of the anion gap for the effect of serum albumin can improve its sensitivity, but many cases will still escape detection. Therefore, the serum anion gap lacks sufficient sensitivity or specificity to serve as a screening tool for lactic acidosis. An elevated blood lactate level is essential for confirmation of the diagnosis. Previously, the definition of lactic acidosis included a blood pH of 7.35 and a serum [HCO3-] of 20 mmol per liter or lower. However, the absence of one or both of these features because of coexisting acid-base disorders does not rule out lactic acidosis.

Morning Report Questions

Q: What general approaches should guide management of lactic acidosis?

A: Restoring tissue perfusion after hemodynamic compromise is essential in the treatment of patients with lactic acidosis. Vasopressors and inotropic agents should be administered as needed. Crystalloid and colloid solutions are both effective in restoring tissue perfusion in patients with sepsis or hypovolemia. Red-cell transfusions should be administered to maintain the hemoglobin concentration at a level above 7 g per deciliter. An adequate PO2 should be maintained by ensuring an appropriate inspired oxygen concentration, with endotracheal intubation and mechanical ventilation as needed. Given the potentially deleterious effects of an acidic environment, some clinicians recommend therapy with intravenous sodium bicarbonate for severe acidemia (blood pH, <7.2). However, the value of bicarbonate therapy in reducing mortality or improving hemodynamics remains unproven. Using dialysis to provide bicarbonate can prevent a decrease in ionized calcium, prevent volume overload and hyperosmolality (potential complications of bicarbonate infusion), and remove substances associated with lactic acidosis, such as metformin. Resuscitative efforts should be complemented by measures targeting the cause or causes of lactic acidosis.

Q: How should a patient be monitored for the development of lactic acidosis?

A: Measurement of the blood lactate level remains the cornerstone of monitoring for lactic acidosis. Lactate can be measured in arterial or venous blood, since the values are virtually interchangeable. An interval of 2 to 6 hours has been suggested for repeat lactate measurements, but this issue has not been examined rigorously. Changes in levels of blood lactate have been used to guide therapy. In a randomized, controlled study, a reduction of at least 20% in serum lactate levels every 2 hours was targeted for the first 8 hours of resuscitation; achievement of this target of lactate clearance was associated with decreased morbidity and mortality. Evidence that in seriously ill patients even lactate levels at the upper end of the normal range are associated with poor clinical outcomes argues for the normalization of blood lactate as a primary goal of therapy.

Table 2. Measures for Monitoring and Goals of Therapy in Patients with Lactic Acidosis.