What are the causes of hyperlactatemia (elevated lactic acid)?

From the Guidelines

Elevated lactic acid levels require immediate medical attention, and treatment should focus on addressing the underlying cause, with the most recent guidelines suggesting against the use of sodium bicarbonate therapy for hemodynamics or vasopressor requirements in patients with hypoperfusion-induced lactic acidemia with pH ≥ 7.15 1. The condition can be caused by various factors, including tissue hypoxia, sepsis, certain medications, or metabolic disorders.

• For severe cases, intravenous fluid resuscitation with normal saline at 20-30 mL/kg is typically initiated to improve circulation and oxygen delivery to tissues.
• Vasopressors like norepinephrine (starting at 0.05-0.1 mcg/kg/min) may be needed if hypotension persists despite fluid therapy.
• Discontinuation of medications that may contribute to lactic acidosis, such as metformin, is essential, as metformin use in the hospital is limited due to the risk of lactic acidosis, especially in patients with cardiac disease, hypoperfusion, renal insufficiency, old age, and chronic pulmonary disease 1.
• Continuous monitoring of lactic acid levels, vital signs, and organ function is crucial during treatment. Lactic acidosis develops when cellular oxygen demand exceeds supply, forcing cells to switch to anaerobic metabolism, which produces lactic acid as a byproduct, creating a vicious cycle that further impairs cellular function and oxygen utilization, making prompt identification and treatment of the underlying cause critical for patient recovery 1. In addition, elevated lactic acid levels can be associated with other conditions, such as acute mesenteric ischemia, and the presence of lactic acidosis in combination with abdominal pain should lead to consideration of early computed tomography angiography (CTA) 1. It is also important to note that the incidence of lactic acidosis has decreased with the use of certain antiretroviral drugs, and patients starting nucleoside reverse transcriptase inhibitor (NRTI) treatment should be made aware of the symptoms of lactic acidemia and asked to report them promptly to their healthcare provider 1.

From the FDA Drug Label

Metformin decreases liver uptake of lactate increasing lactate blood levels which may increase the risk of lactic acidosis, especially in patients at risk. If metformin-associated lactic acidosis is suspected, general supportive measures should be instituted promptly in a hospital setting, along with immediate discontinuation of metformin hydrochloride tablets In metformin hydrochloride tablets treated patients with a diagnosis or strong suspicion of lactic acidosis, prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin

Elevated Lactic Acid is a sign of Lactic Acidosis, a known risk of metformin therapy. The risk of lactic acidosis increases with:

• Renal Impairment: metformin is contraindicated in patients with an eGFR less than 30 mL/min/1.73 m^2
• Age 65 or greater: assess renal function more frequently in elderly patients
• Drug Interactions: concomitant use of metformin with specific drugs may increase the risk of lactic acidosis
• Radiologic studies with contrast: stop metformin hydrochloride tablets at the time of, or prior to, an iodinated contrast imaging procedure in patients with an eGFR between 30 and 60 mL/min/1.73 m^2

If lactic acidosis is suspected, discontinue metformin hydrochloride tablets and institute general supportive measures in a hospital setting. Prompt hemodialysis is recommended to correct the acidosis and remove accumulated metformin 2, 2.

From the Research

Causes of Elevated Lactic Acid

• Lactic acidosis can be caused by various factors, including metformin therapy, especially in patients with renal failure 3, 4, 5
• Other causes of elevated lactic acid levels include tissue hypoperfusion, sepsis, cardiac arrest, trauma, seizure, ischemia, diabetic ketoacidosis, thiamine deficiency, malignancy, liver disease, toxins, overdose, and certain medications 6, 7
• Metformin-associated lactic acidosis (MALA) is a rare but potentially life-threatening complication of metformin therapy, often occurring in patients with underlying renal disease or other comorbidities 3, 4, 5

Diagnosis and Treatment

• Diagnosis of lactic acidosis involves laboratory evaluation, including measurement of serum lactate levels, pH, and anion gap 4, 5, 6
• Treatment of lactic acidosis focuses on addressing the underlying cause, such as discontinuing metformin therapy or managing underlying medical conditions 3, 4, 5
• Continuous renal replacement therapy (CRRT) has been shown to be effective in treating MALA, particularly in patients with acute kidney injury 4, 5
• Prompt recognition and treatment of lactic acidosis are crucial to prevent serious complications and improve patient outcomes 3, 4, 5, 6, 7

Prognosis and Management

• Elevated lactic acid levels are associated with high mortality, especially in severely ill patients 6
• Clinicians should be aware of the various causes of lactate level elevation and tailor specific therapy to the underlying cause 7
• Management of patients with elevated lactic acid levels requires a comprehensive approach, including addressing the underlying cause, providing supportive care, and monitoring patient response to treatment 3, 4, 5, 6, 7