What is the initial management for seizures in patients with hepatic encephalopathy?

Initial Management of Seizures in Hepatic Encephalopathy

Seizures in patients with hepatic encephalopathy should be immediately controlled with phenytoin as the first-line treatment to prevent further elevation of intracranial pressure and cerebral hypoxia. 1

Assessment and Monitoring

• Seizures in hepatic encephalopathy may be a manifestation of the underlying process leading to hepatic coma and intracranial hypertension 1
• Brain CT imaging should be performed to exclude other causes of decreased mental status, though it has limited utility in identifying cerebral edema 1
• Electroencephalogram (EEG) may reveal irregular, diffuse delta/theta slowing consistent with encephalopathy and epileptiform activity 2, 3
• Monitor intracranial pressure in patients with grade III/IV encephalopathy who develop seizures 1

Pharmacological Management

First-Line Treatment

• Phenytoin is recommended as the primary anticonvulsant for controlling seizures in hepatic encephalopathy 1
• Avoid sedatives when possible as they interfere with neurological assessment and have delayed clearance in liver failure 1
• If benzodiazepines are absolutely necessary for uncontrolled seizures, use only minimal doses due to their delayed clearance by the failing liver 1, 4

Alternative Antiepileptic Options

• Newer antiepileptic drugs with minimal hepatic metabolism should be preferred after phenytoin 5:
  • Levetiracetam (available IV) is a good second-line option 5
  • Lacosamide (available IV) can be considered for status epilepticus 5
  • Gabapentin and topiramate have favorable profiles in liver disease 5
• Avoid valproic acid, which undergoes extensive hepatic metabolism and has known hepatotoxicity 5

Management of Underlying Hepatic Encephalopathy

• Simultaneously treat the underlying hepatic encephalopathy to address the root cause of seizures 3:
  • Initiate lactulose (25 mL every 12 hours, titrated to achieve 2-3 soft bowel movements daily) 6
  • Add rifaximin 550 mg twice daily, particularly for prevention of recurrence 6, 2
  • Identify and correct precipitating factors (infections, GI bleeding, electrolyte disturbances, medication non-compliance) 6

Special Considerations

• Seizures may be refractory to standard anticonvulsant therapy until the underlying hepatic encephalopathy is addressed 2, 3
• Non-convulsive status epilepticus should be considered in patients with hepatic encephalopathy and ruled out with EEG 4
• Patients with grade III/IV encephalopathy require intubation for airway protection, which may be especially important during seizure activity 1
• Position patients with head elevated at 30 degrees to reduce intracranial pressure 1

Pitfalls to Avoid

• Delaying seizure treatment can lead to increased intracranial pressure and cerebral hypoxia, worsening outcomes 1
• Overuse of sedative medications can precipitate or worsen hepatic encephalopathy 6, 4
• Failure to identify and treat precipitating factors of hepatic encephalopathy will lead to poor seizure control 6, 2
• Traditional anticonvulsant therapy alone may be ineffective without addressing the underlying liver dysfunction 2, 3

Follow-up Management

• Monitor drug levels of antiepileptic medications as free drug concentrations may be higher in liver disease 4
• Consider discontinuing antiepileptic drugs early once hepatic encephalopathy resolves 4
• Evaluate for liver transplantation in patients with recurrent intractable hepatic encephalopathy 6