What are the causes of hyperlactatemia?

Causes of High Lactate (Hyperlactatemia)

Hyperlactatemia is primarily caused by tissue hypoperfusion and hypoxia, but can also result from non-hypoxic mechanisms including medications, liver dysfunction, and increased metabolic demand. 1

Type A Hyperlactatemia (Hypoxic)

Shock States

• Septic shock: Most common cause of elevated lactate in critically ill patients (34% of severe hyperlactatemia cases) 2
• Cardiogenic shock: Second most common cause (19.3% of severe hyperlactatemia) 2
• Post-cardiac arrest: Following cardiopulmonary resuscitation (13.8% of severe cases) 2
• Hypovolemic shock: Due to hemorrhage or severe dehydration

Regional Tissue Hypoxia

• Mesenteric ischemia: Acute arterial embolism, thrombosis, or non-occlusive mesenteric ischemia 3
• Compartment syndromes: Limb ischemia
• Severe hypoxemia: Respiratory failure

Type B Hyperlactatemia (Non-Hypoxic)

Medication-Induced

• Metformin: Can cause lactic acidosis, especially with renal impairment, hepatic dysfunction, or excessive alcohol intake 4
• Nucleoside reverse transcriptase inhibitors (NRTIs): Can cause mitochondrial toxicity and lactic acidosis 3
• Epinephrine/albuterol: Most commonly identified medications causing hyperlactatemia through β2-adrenergic stimulation 5
• Other medications: Various drugs can cause hyperlactatemia through different mechanisms 5

Metabolic Causes

• Liver dysfunction: Impaired lactate clearance 4
• Diabetic ketoacidosis: Increased metabolic demand
• Glycogen storage diseases: Especially type I 3
• Thiamine deficiency: Impaired pyruvate metabolism
• Alcoholism: Altered redox state

Other Causes

• Seizures: Increased muscle activity
• Malignancy: Altered metabolism in tumor cells
• Severe exercise: Temporary increase in anaerobic metabolism
• Excessive work of breathing: Respiratory muscle fatigue

Diagnostic Approach

Laboratory Assessment

• Lactate levels:

  • Normal: ≤2 mmol/L
  • Moderate elevation: 2-4 mmol/L
  • Severe elevation: >4 mmol/L 1
  • Critical: >10 mmol/L (associated with 78.2% mortality) 2

• Lactate/pyruvate ratio:

  • 20 suggests hypoxic mechanism

  • <20 suggests non-hypoxic mechanism 6, 7

Clinical Correlation

• Sepsis indicators: Fever, tachycardia, hypotension, altered mental status 3
• Shock assessment: Blood pressure, heart rate, peripheral perfusion
• Medication review: Focus on metformin, epinephrine, albuterol, NRTIs 3, 4, 5

Prognostic Significance

• Lactate clearance: 12-hour lactate clearance <32.8% associated with 96.6% ICU mortality 2
• Timing of hyperlactatemia: Development after 24 hours in ICU has worse prognosis (89.1% mortality) than early hyperlactatemia (69.9% mortality) 2
• Normalization timeline: Lactate normalization within 24 hours associated with 100% survival, compared to 13.6% survival if normalization occurs beyond 48 hours 1

Management Considerations

• Identify and treat underlying cause: Most important step
• Fluid resuscitation: For hypovolemia and sepsis (30 mL/kg IV crystalloid within first 3 hours) 1
• Vasopressors: For persistent hypotension despite fluid resuscitation, targeting MAP ≥65 mmHg 1
• Antibiotics: Within first hour if infection is suspected 1
• Discontinue contributing medications: Especially metformin in patients with renal impairment 4
• Monitor lactate clearance: Target at least 10% reduction within 2-4 hours 1

Important Caveats

• Lactate elevation may not always indicate tissue hypoxia; stress-induced accelerated aerobic metabolism can cause hyperlactatemia without hypoperfusion 8
• Epinephrine-induced hyperlactatemia is common and may not require specific intervention 6
• Normal global oxygen delivery indices may exist despite regional tissue hypoperfusion 6
• Lactate measurement requires standardized collection techniques (prechilled tubes, immediate processing) 3
• Lactate-guided resuscitation is associated with significant mortality reduction compared to resuscitation without lactate monitoring 1