What are the most common causes of lactic acidosis?

Most Common Causes of Lactic Acidosis

The most common causes of lactic acidosis are tissue hypoxia (type A) and impaired lactate clearance (type B), with tissue hypoxia from shock, sepsis, and cardiac failure being the predominant mechanisms in clinical practice. 1, 2

Classification and Major Causes

Type A Lactic Acidosis (Tissue Hypoxia)

• Shock states
  • Septic shock
  • Cardiogenic shock
  • Hypovolemic shock
  • Obstructive shock (e.g., pulmonary embolism)
• Severe hypoxemia
  • Respiratory failure
  • Severe anemia
• Regional tissue hypoperfusion
  • Mesenteric ischemia
  • Limb ischemia
  • Compartment syndrome

Type B Lactic Acidosis (Non-Hypoxic)

• Medication-induced
  • Metformin (especially with renal impairment) 3, 4
  • Nucleoside reverse transcriptase inhibitors
  • Propofol (with prolonged infusion)
• Impaired lactate clearance
  • Severe liver dysfunction
  • Renal failure
• Metabolic causes
  • Thiamine deficiency
  • Diabetic ketoacidosis
  • Alcoholic ketoacidosis
  • Inborn errors of metabolism
• Malignancy
  • Lymphoma
  • Leukemia
  • Solid tumors with high glycolytic rates

Metformin-Associated Lactic Acidosis (MALA)

While relatively rare, MALA deserves special attention as metformin is widely prescribed:

• Risk factors for MALA 5, 4:
  • Renal impairment (eGFR <45 mL/min/1.73m²)
  • Advanced age (especially >80 years)
  • Acute kidney injury
  • Liver dysfunction
  • Congestive heart failure
  • Hypoxic conditions
  • Excessive alcohol intake
  • Iodinated contrast procedures
  • Dehydration or volume depletion

The FDA and clinical guidelines recommend 3, 4:

• Avoiding metformin when eGFR <30 mL/min/1.73m²
• Reducing dose to 1000mg daily when eGFR is 30-44 mL/min/1.73m²
• Temporarily discontinuing during acute illness, especially with dehydration or hypotension

D-Lactic Acidosis

A special form of lactic acidosis occurs in patients with short bowel syndrome with preserved colon 3:

• Caused by bacterial fermentation of unabsorbed carbohydrates
• Presents with neurological symptoms and confusion
• Treatment includes restricting mono/oligosaccharides and antibiotics

Clinical Approach to Lactic Acidosis

1. Identify and treat the underlying cause:

   • Restore tissue perfusion in shock states
   • Improve oxygenation in respiratory failure
   • Discontinue offending medications
   • Treat underlying infection in sepsis

2. Laboratory evaluation:

   • Arterial blood gas
   • Serum lactate level
   • Complete metabolic panel
   • Toxicology screen when appropriate
   • Drug levels (e.g., metformin) when suspected

3. Management principles:

   • Focus on treating the underlying cause rather than the acidosis itself
   • Judicious fluid resuscitation in hypovolemic states
   • Vasopressors for persistent hypotension
   • Consider renal replacement therapy in severe cases of MALA 6
   • Sodium bicarbonate has limited value and may increase lactate production 2

Important Clinical Pearls

• Sepsis can cause lactic acidosis through multiple mechanisms beyond tissue hypoxia, including increased aerobic glycolysis and decreased lactate clearance 1
• Metformin-associated lactic acidosis can occur without other predisposing factors in patients with deteriorating renal function 7
• The mortality rate of severe lactic acidosis remains high, particularly when pH falls below 7.2
• Early recognition and treatment of the underlying cause is the cornerstone of management