What are the causes and treatments of metabolic encephalopathy?

Metabolic Encephalopathy: Causes and Treatment

Causes of Metabolic Encephalopathy

Metabolic encephalopathy results from systemic disturbances that impair brain function through multiple mechanisms including accumulation of toxic metabolites, energy failure, cerebral edema, and altered neurotransmitter function. 1, 2

Primary Metabolic Derangements

Hepatic causes:

• Hepatic encephalopathy from cirrhosis is characterized by hyperammonemia and represents one of the most common metabolic encephalopathies 3, 4
• Acute liver failure with coagulopathy and synthetic dysfunction 3

Renal causes:

• Uremic encephalopathy from acute or chronic kidney failure 4, 5
• Dialysis-related encephalopathy from aluminum toxicity 5

Endocrine/metabolic disorders:

• Hypoglycemia and hyperglycemia (diabetic ketoacidosis, hyperosmolar hyperglycemic state) 3, 4
• Hypo- and hyperthyroidism 3, 4
• Hyponatremia (particularly <130 mmol/L) 3, 4
• Hypokalemia and hypomagnesemia 4, 6

Hypoxic-ischemic injury:

• Respiratory failure with hypercapnia 4, 6
• Cardiac arrest or severe hypotension 7

Toxic causes:

• Medication toxicity (benzodiazepines, opioids, anticholinergics) 3, 5
• Alcohol intoxication or withdrawal 3, 4
• Drug overdose (salicylates, methanol, ethylene glycol) 3

Precipitating Factors in Cirrhotic Patients

The following precipitants are present in approximately 50% of hepatic encephalopathy cases and their correction leads to symptom improvement in 90% of patients: 3

• Gastrointestinal bleeding 3
• Infections (spontaneous bacterial peritonitis, pneumonia, urinary tract infection) 3
• Dehydration from diuretics or gastrointestinal losses 3
• Constipation 3
• Proton pump inhibitor use (promotes small intestinal bacterial overgrowth and dysbiosis) 3
• Acute kidney injury 3

Nutritional Deficiencies

• Thiamine deficiency (Wernicke's encephalopathy) 3, 8
• Vitamin E deficiency 3

Treatment Approach

Step 1: Immediate Stabilization and Diagnosis

Airway protection is critical—patients with grade III/IV encephalopathy require intubation. 6

Essential diagnostic workup includes: 3, 4, 6

• Complete metabolic panel (electrolytes, glucose, renal function, liver function tests) 4, 5
• Complete blood count and inflammatory markers 3
• Arterial blood gas 3
• Ammonia level (especially if hepatic encephalopathy suspected) 4, 5
• Toxicology screen including alcohol level 6, 5
• Thyroid-stimulating hormone 3
• Brain imaging (MRI preferred over CT) to exclude structural lesions 3, 5
• Electroencephalogram to rule out non-convulsive status epilepticus 3, 5

Step 2: Identify and Correct the Underlying Cause

Correction of the precipitating factor is paramount and resolves nearly 90% of cases, particularly in hepatic encephalopathy. 6, 3

Specific interventions based on etiology:

For hepatic encephalopathy: 9

• Lactulose 30-45 mL (20-30 grams) orally three to four times daily, titrated to produce 2-3 soft bowel movements per day 9
• For rapid laxation in acute presentations, give lactulose 30-45 mL hourly until laxative effect achieved, then reduce to maintenance dosing 9
• Lactulose enema (300 mL lactulose mixed with 700 mL water/saline, retained 30-60 minutes, repeated every 4-6 hours) if oral route unavailable due to aspiration risk or coma 9
• Rifaximin as add-on therapy or alternative when lactulose not tolerated 6

For diabetic emergencies: 3

• Intravenous 10% dextrose/normal saline at 1.5-2.0 times maintenance rate to maintain normoglycemia 3
• Insulin therapy for diabetic ketoacidosis or hyperosmolar hyperglycemic state 3

For electrolyte disturbances: 6

• Correct hyponatremia cautiously (maintain sodium >130 mmol/L, ideally >135 mmol/L) 3
• Supplement phosphate, magnesium, and potassium as needed 6

For hypoglycemia:

• Continuous glucose infusions to maintain adequate levels 6

For thiamine deficiency:

• Thiamine supplementation before glucose administration 3

Step 3: Supportive Care

Positioning and monitoring: 6

• Elevate head of bed to 30 degrees to reduce intracranial pressure 6
• Manage patients with higher grades of encephalopathy in intensive care setting 6

Fluid management:

• Isotonic saline (0.9% NaCl) at 15-20 mL/kg/hour initially for volume expansion 3
• Maintain adequate intravascular volume 6

Seizure management:

• Phenytoin is preferred anticonvulsant in hepatic encephalopathy 6

Nutritional support: 6

• Start low-dose enteral nutrition once life-threatening metabolic derangements controlled 6
• Maintain protein intake at 1.5 g/kg/day—do not restrict protein in hepatic encephalopathy as this worsens catabolism 6

Step 4: Prevention of Recurrence

For hepatic encephalopathy prevention: 3

• Monitor blood sodium levels regularly in decompensated cirrhosis 3
• Limit proton pump inhibitors to strict validated indications only 3
• Contraindicate benzodiazepines in patients with decompensated cirrhosis 3
• Continue lactulose long-term to prevent recurrence 9

Advanced therapy:

• Recurrent intractable hepatic encephalopathy with liver failure is an indication for liver transplantation 6

Critical Pitfalls to Avoid

Multiple metabolic derangements often coexist and have synergistic effects—hyponatremia and sepsis can independently produce encephalopathy and precipitate hepatic encephalopathy. 3, 5

Do not assume metabolic encephalopathy without excluding: 3, 4

• Structural brain lesions (stroke, hemorrhage, subdural hematoma) 3
• Meningitis or encephalitis (perform lumbar puncture if infection cannot be excluded clinically, after ruling out increased intracranial pressure) 6
• Non-convulsive status epilepticus 3
• Intracranial bleeding 3
• Drug intoxication 3

Resolution of brain dysfunction may be protracted despite normalization of laboratory values—improvement may not begin for 48 hours or longer. 9, 2

Asterixis (flapping tremor) is strongly suggestive of metabolic encephalopathy and should prompt immediate evaluation. 4, 5