What are the causes of metabolic encephalopathy?

Causes of Metabolic Encephalopathy

Metabolic encephalopathy is primarily caused by hepatic failure, renal dysfunction, electrolyte disorders (especially hyponatremia), diabetes, sepsis, and thiamine deficiency, with each requiring specific diagnostic workup and targeted management. 1, 2

Major Categories of Metabolic Encephalopathy

Hepatic Encephalopathy

• Type A: Resulting from acute liver failure
• Type B: Resulting from portosystemic bypass or shunting
• Type C: Resulting from cirrhosis 1

Other Common Causes

1. Diabetic Metabolic Disturbances:

   • Hypoglycemia
   • Diabetic ketoacidosis
   • Hyperosmolar state
   • Lactic acidosis 1

2. Electrolyte Disorders:

   • Hyponatremia (independent risk factor for encephalopathy development)
   • Hypercalcemia 1

3. Toxic-Metabolic Causes:

   • Alcohol (intoxication, withdrawal, Wernicke's encephalopathy)
   • Medications (benzodiazepines, neuroleptics, opioids)
   • Heavy metal toxicity 1, 2

4. Nutritional Deficiencies:

   • Thiamine deficiency (particularly in alcoholic liver disease)
   • Vitamin B12 deficiency
   • Folate deficiency 1, 2

5. Systemic Conditions:

   • Sepsis and systemic inflammatory response syndrome (SIRS)
   • Renal dysfunction
   • Severe medical stress with organ failure 1

6. Other Important Causes:

   • Pancreatic encephalopathy
   • Uremic encephalopathy
   • Central pontine myelinolysis (from rapid sodium correction)
   • Fat embolism syndrome 3, 4

Diagnostic Approach

Essential Laboratory Tests

• Complete blood count
• Comprehensive metabolic panel (including liver and kidney function)
• Ammonia levels (particularly for suspected hepatic encephalopathy)
• Thyroid function tests
• Toxicology screen
• Vitamin levels (B12, folate, thiamine) 2

Imaging

• Brain CT or MRI to rule out structural causes and assess for cerebral edema 2

Pathophysiological Mechanisms

Metabolic encephalopathy can develop through several mechanisms:

• Focal or global cerebral edema
• Alterations in neurotransmitter function
• Accumulation of uncleared toxic metabolites (e.g., ammonia in hepatic encephalopathy)
• Postcapillary venule vasogenic edema
• Energy failure at the cellular level 5

Important Clinical Considerations

Precipitating Factors for Hepatic Encephalopathy

• Gastrointestinal bleeding
• Infection/sepsis
• Constipation
• Excessive protein intake
• Dehydration or excessive diuresis
• Electrolyte abnormalities (especially hyponatremia and hypokalemia)
• Medication effects (benzodiazepines, opioids)
• Acute liver dysfunction 2

Common Pitfalls to Avoid

• Overlooking occult infection as a precipitating factor
• Excessive diuresis leading to hypovolemia and worsening renal function
• Rapid correction of hyponatremia (risk of central pontine myelinolysis)
• Administering sedatives or opioids that may worsen encephalopathy
• Relying solely on ammonia levels to guide management decisions 2

Management Principles

Management should focus on treating the underlying cause while providing supportive care:

1. For Hepatic Encephalopathy:

   • Lactulose as first-line therapy (reduces blood ammonia by 25-50%) 6
   • Rifaximin as add-on therapy for recurrent episodes 2
   • Avoid sedatives, especially benzodiazepines 2

2. For Nutritional Deficiencies:

   • Immediate IV thiamine administration before glucose in suspected Wernicke's encephalopathy 1
   • Adequate protein intake (0.8-1.2 g/kg/day) 2

3. For Sepsis-Related Encephalopathy:

   • Broad-spectrum antibiotics for suspected infection 2
   • Supportive care addressing organ dysfunction

4. For Electrolyte Disturbances:

   • Careful correction of electrolyte abnormalities, especially sodium (target 140-145 mmol/L) 2
   • Close monitoring of potassium levels, especially with diuretic therapy 2

Metabolic encephalopathy, while often considered reversible, is associated with increased mortality, prolonged hospital stays, and worse long-term cognitive outcomes, making prompt recognition and treatment essential 7.