What are the causes of elevated lactic acid levels other than sepsis?

Causes of Elevated Lactic Acid Other Than Sepsis

Elevated lactic acid levels can result from multiple pathophysiological processes beyond sepsis, including tissue hypoxia from various causes, medication effects, metabolic disorders, and specific disease states.

Primary Mechanisms of Lactic Acid Elevation

Tissue Hypoxia and Hypoperfusion

• Decreased oxygen delivery states:
  • Cardiogenic shock 1, 2
  • Hypovolemic shock 1
  • Obstructive shock 3
  • Severe hypoxemia 1, 4
  • Low cardiac output states 1

Medication-Induced

• Metformin: Decreases liver uptake of lactate, increasing blood levels and risk of lactic acidosis, especially in patients with renal impairment 5
• Drug interactions: Medications that impair renal function, cause hemodynamic changes, or interfere with acid-base balance 5

Metabolic Causes

• Diabetic ketoacidosis: Can cause lactic acidosis through multiple mechanisms 6
• Liver disease: Impaired lactate clearance due to hepatic dysfunction 5, 3
• Renal failure: Failure to excrete acid produced by normal metabolic processes 1
• D-lactic acidosis: Occurs in patients with short bowel and preserved colon due to bacterial degradation of carbohydrates 1

Other Significant Causes

• Malignancies: Particularly hematologic malignancies like acute lymphoblastic leukemia 7
• Excessive exercise: Metabolic acidosis occurs at peak exercise when oxygen delivery is insufficient to meet demand 1
• Alcohol abuse: May induce lactic acid under-use or increased production 6
• Seizures: Grand mal seizures can cause type B lactic acidosis 6
• Thiamine deficiency: Can lead to impaired pyruvate metabolism 6
• Congenital enzyme deficiencies: Affect normal lactate metabolism 6

Classification of Lactic Acidosis

Type A Lactic Acidosis

• Results from tissue hypoxia and inadequate oxygen delivery 8
• Most common form in critically ill patients 8
• Associated with conditions like shock, trauma, and severe hypoxemia 8

Type B Lactic Acidosis

• Occurs without evidence of tissue hypoperfusion or shock 8, 6
• Causes include:
  • Medications (metformin) 5
  • Liver failure 6
  • Malignancies 7
  • Congenital enzyme deficiencies 6
  • Thiamine deficiency 6
  • Diabetes mellitus 6

Clinical Implications and Assessment

• Blood lactate serves as a sensitive marker to estimate and monitor the extent of tissue hypoperfusion 1
• Lactate >4 mmol/L indicates significant tissue hypoperfusion, even in the absence of hypotension 4
• Serial lactate measurements provide early and objective evaluation of patient response to therapy 1
• Lactate levels may be particularly important in penetrating trauma where vital signs don't reliably reflect injury severity 1

Special Considerations

D-Lactic Acidosis

• Only occurs in patients with short bowel and preserved colon 1
• Caused by colonic bacteria degrading fermentable carbohydrates 1
• Can cause confusion and metabolic acidosis with large anion gap 1
• Treatment includes restricting mono/oligosaccharides, encouraging polysaccharide intake, thiamine supplements, and antibiotics 1

Metformin-Associated Lactic Acidosis

• Characterized by elevated blood lactate (>5 mmol/L), anion gap acidosis, and increased lactate:pyruvate ratio 5
• Risk factors include:
  • Renal impairment 5
  • Age >65 years 5
  • Hypoxic states (heart failure, MI, sepsis) 5
  • Excessive alcohol intake 5
  • Hepatic impairment 5
  • Radiologic studies with contrast 5

Clinical Pearls

• Persistently elevated lactate without evidence of inadequate oxygen delivery should prompt consideration of type B lactic acidosis 7
• Lactate formation during critical illness is not entirely related to tissue hypoxia or reversible by increasing oxygen delivery 8
• In patients with short bowel syndrome, consider D-lactic acidosis as a cause of confusion and acidosis 1
• Alcohol consumption may affect the reliability of lactate determination in traumatic injury 1

Remember that elevated lactate is a marker of physiological stress that requires prompt investigation of the underlying cause to guide appropriate management and improve outcomes.