Non-Infectious Causes of Elevated Lactic Acid
Elevated lactic acid levels can result from numerous non-infectious conditions that affect oxygen delivery, metabolism, or clearance of lactate. Understanding these causes is essential for proper diagnosis and management of patients with hyperlactatemia.
Cardiovascular Causes
- Shock states - including cardiogenic, hypovolemic, and obstructive shock lead to tissue hypoperfusion and increased lactate production 1
- Cardiac failure - decreased cardiac output reduces tissue perfusion 1
- Myocardial infarction - causes regional hypoperfusion and can trigger systemic inflammatory response 1
Medication-Related Causes
- Metformin - the most common drug-associated cause of lactic acidosis, especially in patients with renal impairment 2
- Metformin decreases liver uptake of lactate, increasing blood lactate levels
- Risk factors include: eGFR <45 mL/min/1.73m², age >65 years, hepatic impairment, and excessive alcohol intake 2
- Vasopressors - high-dose vasoactive drugs can cause non-occlusive mesenteric ischemia (NOMI) leading to lactic acidosis 1
Hepatic Causes
- Liver disease - impairs lactate clearance as the liver is responsible for up to 70% of lactate metabolism 1
- Hepatic impairment - reduces lactate clearance resulting in higher lactate blood levels 2
Metabolic Disorders
- Diabetic ketoacidosis (DKA) - often presents with elevated lactate levels alongside ketoacidosis 1
- Thiamine deficiency - impairs pyruvate metabolism, leading to lactate accumulation 1
Tissue Hypoxia/Ischemia
- Mesenteric ischemia - all forms (arterial embolism, arterial thrombosis, venous thrombosis, and non-occlusive) can cause elevated lactate 1
- Compartment syndrome - restricts blood flow to tissues 1
- Seizures - increased muscle activity and oxygen consumption 3
- Severe anemia - reduces oxygen-carrying capacity 3
Other Causes
- Labor and delivery - physiologic stress during childbirth can elevate lactate levels 1
- Malignancy - altered metabolism and increased glycolysis in cancer cells 3
- Excessive muscular activity - strenuous exercise increases lactate production 3
- Toxins and alcohol - disrupt normal cellular metabolism 2
- Abdominal compartment syndrome - impairs perfusion to abdominal organs 1
Clinical Pearls
- Normal lactate levels are typically below 2 mmol/L 1
- Lactate >5 mmol/L is considered abnormal, and levels >10 mmol/L indicate serious and potentially life-threatening conditions 1
- Elevated lactate is not always due to tissue hypoxia; consider other causes before attributing to sepsis 1
- D-dimer elevation often accompanies lactic acidosis in conditions like mesenteric ischemia 1
Common Pitfalls
- Misattribution to sepsis - not all elevated lactate indicates infection; consider non-infectious causes 1
- Overlooking medications - always review medication list, particularly metformin 2
- Delayed diagnosis - lactic acidosis in combination with abdominal pain should prompt consideration of mesenteric ischemia, even when the patient appears clinically stable 1
- Sample handling errors - lactate measurement requires standardized collection in prechilled fluoride-oxalate tubes, transported immediately on ice, and processed within 4 hours 1
Remember that elevated lactate is a marker of an underlying process rather than a disease itself, and treatment should be directed at the underlying cause.