What types of metabolic encephalopathies can occur after cocaine-induced malignant hyperthermia or liver failure, both immediately and in the days to weeks following the event?

Metabolic Encephalopathies Following Cocaine-Induced Malignant Hyperthermia or Liver Failure

Patients who experience cocaine-induced malignant hyperthermia or liver failure can develop several types of metabolic encephalopathies both immediately after use and in the days to weeks following the event, with hepatic encephalopathy being the most significant concern for long-term morbidity and mortality.

Immediate Metabolic Encephalopathies (Hours to Days)

1. Hyperthermia-Related Encephalopathy

• Cocaine directly impairs thermoregulation by shifting the threshold for cutaneous vasodilation and sweating, preventing normal heat dissipation 1
• Presents with:
  • Altered mental status ranging from agitation to delirium
  • Seizures (potentially status epilepticus)
  • Hyperthermia (often >40°C)
  • Autonomic instability

2. Acute Ischemic Encephalopathy

• Results from cocaine-induced vasoconstriction and hypertensive crisis
• Cocaine blocks presynaptic reuptake of neurotransmitters (norepinephrine and dopamine), leading to sympathetic activation 2
• May present with:
  • Focal neurological deficits
  • Altered consciousness
  • Seizures

3. Rhabdomyolysis-Associated Encephalopathy

• Cocaine-induced hyperthermia frequently leads to rhabdomyolysis 3, 4, 5
• Metabolic derangements include:
  • Hyperkalemia
  • Hypocalcemia
  • Metabolic acidosis
  • Acute kidney injury with uremic encephalopathy

Delayed Metabolic Encephalopathies (Days to Weeks)

1. Hepatic Encephalopathy

• Most significant long-term concern following cocaine-induced liver injury

• Classified based on severity:

  • Covert HE: Subtle cognitive impairment detectable only on psychometric testing
  • Overt HE: Clinically apparent neuropsychiatric abnormalities including disorientation, asterixis, and altered consciousness 2

• Clinical presentation includes:

  • Progressive disorientation to time and space
  • Personality changes (apathy, irritability, disinhibition)
  • Sleep-wake cycle disturbances
  • Asterixis ("flapping tremor")
  • Extrapyramidal signs (hypomimia, bradykinesia, parkinsonian-like tremor)
  • In severe cases: stupor and coma 2

• Diagnosis requires:

  • Blood tests (ammonia levels, electrolytes, liver function)
  • Exclusion of other causes of encephalopathy
  • Hepatic Doppler ultrasound to assess portal hypertension 2

2. Uremic Encephalopathy

• May develop secondary to acute kidney injury from rhabdomyolysis
• Presents with:
  • Cognitive slowing
  • Asterixis (similar to HE)
  • Myoclonus
  • Seizures in severe cases

3. Electrolyte Disturbance Encephalopathies

• Hyponatremia-associated encephalopathy
  • Common in liver failure
  • Increases risk of developing HE 2
  • Presents with confusion, seizures, and altered consciousness

Differential Diagnosis and Workup

When evaluating encephalopathy in patients with history of cocaine use and liver injury, it's essential to consider several conditions that may mimic or coexist with metabolic encephalopathies:

1. Required investigations 2:

   • Blood analysis: PT/INR, factor V, glucose, arterial blood gases, lactate, ammonia
   • Hepatic Doppler ultrasound
   • Echocardiography
   • Toxicology screen (cocaine, amphetamines)
   • Serum electrolytes, renal function

2. Differential diagnoses to consider 2:

   • Wernicke's encephalopathy (thiamine deficiency, common in alcoholics)
   • Hypoglycemia
   • Septic encephalopathy
   • Intracranial hemorrhage
   • Seizures and post-ictal states
   • Withdrawal syndromes

Management Approach

1. Immediate management of cocaine-induced hyperthermia:

   • Aggressive cooling measures
   • Benzodiazepines for agitation and seizures
   • Avoid beta-blockers alone (can worsen cocaine-induced vasoconstriction)
   • Consider combined alpha and beta blockade (e.g., labetalol) only after vasodilator administration 2

2. Management of hepatic encephalopathy 2:

   • Systematic administration of N-acetylcysteine regardless of suspected etiology
   • Early contact with transplant unit for severe cases
   • Maintain serum sodium between 140-145 mmol/L
   • Tracheal intubation and sedation for progressive HE (Glasgow <8)
   • Avoid benzodiazepines and psychotropic drugs

3. What NOT to do 2:

   • Administer sedatives like benzodiazepines and psychotropic drugs
   • Use treatments to lower ammonia levels (lactulose, rifaximin) in acute setting
   • Use nephrotoxic drugs including NSAIDs
   • Routinely correct coagulation (restrict clotting factors unless active bleeding)

Long-term Considerations

Patients who survive acute cocaine-induced malignant hyperthermia or liver failure require close monitoring for persistent neurological sequelae:

• Hepatic myelopathy - characterized by severe motor abnormalities with relatively mild mental dysfunction 2
• Persistent extrapyramidal and pyramidal signs
• Cognitive impairment that may persist despite resolution of acute liver injury

The prognosis of acute liver failure has improved in recent years, with a 2-year survival rate of about 90% in the event of transplantation 2. However, patients with recurrent hepatic encephalopathy have a 40% cumulative risk of another recurrence within 6 months despite treatment 2.