From the Guidelines
Elevated lactic acid levels are primarily caused by conditions that lead to tissue hypoxia or impaired lactate clearance, such as intense exercise, shock states, severe infections, and respiratory failure. The most common causes of elevated lactic acid levels include:
- Intense exercise, where muscles work harder than oxygen delivery allows
- Shock states like sepsis, severe trauma, or cardiac failure where blood flow is compromised
- Severe infections that increase metabolic demands
- Respiratory failure limiting oxygen intake Certain medications like metformin, some HIV drugs, and propofol can also raise lactate levels 1. Medical conditions affecting lactate clearance include liver disease and kidney failure 1. Rare genetic disorders of metabolism may cause chronic elevation. Diabetic ketoacidosis and alcohol abuse can disrupt normal metabolism, leading to lactic acidosis. According to the most recent study in 2022, elevated serum lactate levels > 2 mmol/l is associated with irreversible intestinal ischemia hazard ratio: 4.1 (95% CI: 1.4–11.5; p < 0.01) in case of acute mesenteric ischemia 1. Treatment focuses on addressing the underlying cause, whether improving oxygen delivery, treating infection, discontinuing problematic medications, or supporting organ function. Persistent unexplained elevation requires thorough investigation to identify and address the root cause. It is essential to note that lactate levels can be influenced by various factors, and a comprehensive evaluation is necessary to determine the underlying cause of elevated lactic acid levels. In clinical practice, it is crucial to consider the patient's overall clinical presentation, medical history, and laboratory results to guide diagnosis and treatment. The management of elevated lactic acid levels should prioritize the identification and treatment of the underlying cause, as well as supportive care to prevent further complications. By addressing the root cause of elevated lactic acid levels, healthcare providers can improve patient outcomes and reduce the risk of morbidity and mortality. In summary, elevated lactic acid levels are a significant indicator of tissue hypoxia or impaired lactate clearance, and prompt identification and treatment of the underlying cause are crucial to prevent adverse outcomes.
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. Metformin-associated lactic acidosis was characterized by elevated blood lactate concentrations (>5 mmol/L), anion gap acidosis (without evidence of ketonuria or ketonemia), and an increased lactate: pyruvate ratio;
The cause of elevated lactic acid levels is metformin decreasing liver uptake of lactate, increasing lactate blood levels, especially in patients at risk, such as those with:
- Renal impairment
- Drug interactions that impair renal function or increase metformin accumulation
- Age 65 or greater, due to a greater likelihood of having hepatic, renal, or cardiac impairment 2
From the Research
Causes of Elevated Lactic Acid Levels
Elevated lactic acid levels can be caused by various factors, including:
- Hypoxia, which can be caused by septic, cardiogenic, hypovolemic, or obstructive shock 3, 4
- Specific pathologies, such as liver disease 3
- Use of certain drugs, including metformin 3, 5
- Presence of toxins 3, 4
- Trauma 3, 4
- Medication-induced hyperlactatemia and lactic acidosis, which can be caused by a variety of medications, including epinephrine and albuterol 5
- Type B lactic acidosis, which can be caused by underlying conditions such as cancer 6
- Sepsis, which is a common cause of lactic acidosis in critically ill patients 4, 6
Underlying Mechanisms
The underlying mechanisms of elevated lactic acid levels can be complex and multifactorial. Lactic acidosis can result from tissue hypoperfusion, which can lead to increased production of lactic acid 4. Additionally, certain medications and underlying conditions can increase lactic acid production or decrease its clearance 5.
Clinical Significance
Elevated lactic acid levels can have significant clinical implications, including increased mortality and morbidity in critically ill patients 3, 4. It is essential to identify the underlying cause of elevated lactic acid levels to provide appropriate treatment and prevent poor clinical outcomes 3, 4.