What causes severe lactic acidosis with elevated anion gap and high lactic acid levels?

Causes of Severe Lactic Acidosis with Elevated Anion Gap

A lactic acid level of 27 with an anion gap of 40 is most likely due to severe tissue hypoperfusion (shock), ethylene glycol poisoning, or metformin-associated lactic acidosis, with immediate treatment needed to address the underlying cause and correct the acidosis. 1, 2, 3

Common Causes of Severe Lactic Acidosis

Type A Lactic Acidosis (Tissue Hypoxia/Hypoperfusion)

• Circulatory shock (cardiogenic, septic, hypovolemic)
• Severe hypoxemia
• Carbon monoxide poisoning
• Severe anemia
• Seizures or excessive muscle activity

Type B Lactic Acidosis (Non-Hypoxic Causes)

• Medications/toxins:

  • Ethylene glycol poisoning (anion gap >27 mmol/L) 1
  • Metformin (especially with renal dysfunction)
  • Nucleoside reverse transcriptase inhibitors 1, 2
  • Alcoholic ketoacidosis (mixed picture) 1
  • Salicylates, methanol, paraldehyde 1

• Metabolic disorders:

  • Diabetic ketoacidosis (mixed picture with ketones) 1
  • Glycogen storage disease (can cause extreme lactate levels) 4
  • Thiamine deficiency
  • Liver failure (impaired lactate clearance)

Diagnostic Approach

Immediate Laboratory Assessment

• Arterial blood gases (to assess pH and bicarbonate)
• Complete blood count
• Comprehensive metabolic panel
• Serum ketones
• Serum osmolality (calculate osmolar gap)
• Toxicology screen
• Blood cultures if infection suspected

Critical Findings in This Case

• Lactic acid of 27 mmol/L (severely elevated; normal is ≤2 mmol/L) 2
• Anion gap of 40 mmol/L (severely elevated; normal is 8-12 mmol/L)
• These values suggest:
  • Critical tissue hypoperfusion/shock
  • Possible ethylene glycol poisoning (anion gap >27 strongly suggests this) 1
  • Possible severe metformin-associated lactic acidosis

Important Diagnostic Considerations

• Ethylene glycol poisoning should be strongly considered with anion gap >27 mmol/L 1
• Calculate osmolar gap - elevated gap (>10) with high anion gap suggests toxic alcohol ingestion 1
• Glycolate from ethylene glycol can falsely elevate lactate readings on some analyzers 1
• Anion gap alone has limited sensitivity (40-80% miss rate) for detecting lactic acidosis 5

Management

Immediate Interventions

1. Fluid resuscitation: 30 mL/kg IV crystalloid if signs of hypoperfusion 2
2. Vasopressor support: If hypotension persists despite fluid resuscitation 2
3. Sodium bicarbonate: For severe acidosis (pH <7.1) 3
   • Caution: May increase lactate production 6
4. Identify and treat underlying cause:
   • If ethylene glycol poisoning: Consider fomepizole and hemodialysis 1
   • If shock: Address underlying cause (antibiotics for sepsis, etc.)
   • If metformin-associated: Consider hemodialysis

Monitoring

• Serial lactate measurements every 4-6 hours to assess clearance 2
• Target lactate clearance of at least 10-20% 2
• Continuous hemodynamic monitoring
• Regular arterial blood gases to monitor pH and bicarbonate

Special Considerations

• Ethylene glycol poisoning: ECTR (extracorporeal treatment) is strongly recommended if anion gap >27 mmol/L in the context of ethylene glycol exposure 1
• Liver dysfunction: May require more aggressive intervention due to impaired lactate metabolism 2
• Metformin: Risk of lactic acidosis is higher in patients with severe renal or cardiac dysfunction 6
• Diabetic ketoacidosis: May present with mixed picture of ketoacidosis and lactic acidosis 1

Pitfalls to Avoid

• Don't rely solely on anion gap to detect lactic acidosis - direct lactate measurement is essential 5
• Don't delay treatment while waiting for a definitive diagnosis in severely acidotic patients
• Don't miss ethylene glycol poisoning - consider this diagnosis with very high anion gaps 1
• Don't overlook the possibility of mixed acid-base disorders

Remember that extremely high lactate levels (>20 mmol/L) with severely elevated anion gaps are life-threatening and require immediate, aggressive intervention to address both the underlying cause and the metabolic derangements.