What is the recommended treatment for seizure secondary to liver failure?

Management of Seizures Secondary to Liver Failure

Phenytoin is recommended as the primary anticonvulsant for controlling seizures in hepatic encephalopathy, while newer antiepileptic drugs with minimal hepatic metabolism such as levetiracetam should be considered as first-line therapy in patients with advanced liver disease. 1, 2

First-Line Treatment Options

• Phenytoin is recommended as the primary anticonvulsant for controlling seizures specifically in hepatic encephalopathy 3, 1
• For patients with advanced liver disease, newer antiepileptic drugs with minimal hepatic metabolism should be preferred 2:
  • Levetiracetam (available in IV form for acute management) 2, 4
  • Lacosamide (available in IV form for acute management) 2
  • Gabapentin 2
  • Pregabalin 2
  • Topiramate 2

Management of Underlying Hepatic Encephalopathy

• Treat the underlying hepatic encephalopathy simultaneously to address the root cause of seizures 1, 5
• Lactulose is FDA-approved for treatment of portal-systemic encephalopathy and reduces blood ammonia levels by 25-50%, which typically improves mental status 6
• N-acetylcysteine therapy is recommended for patients with acute liver failure regardless of etiology to improve morbidity and mortality 3

Medications to Avoid

• Avoid medications undergoing extensive hepatic metabolism when possible 2:
  • Valproic acid (should be used as a drug of last resort) 2
  • Felbamate (should be used as a drug of last resort) 2
• Use benzodiazepines only in minimal doses if absolutely necessary due to their delayed clearance in liver failure 3, 1
• Avoid metronidazole as it may reduce seizure threshold 7

Monitoring and Supportive Care

• Position patients with head elevated at 30 degrees to help reduce intracranial pressure 3, 1
• Monitor intracranial pressure in patients with grade III/IV encephalopathy who develop seizures 1
• Consider intubation for airway protection in patients with grade III/IV encephalopathy, especially during seizure activity 1
• Avoid patient stimulation and maneuvers that cause straining, as these may increase intracranial pressure 3

Evidence for Levetiracetam in Liver Disease

• Levetiracetam appears to be safe for critically ill patients when dosing is adjusted for renal function 4
• In a case series of 14 patients with epilepsy and liver disease treated with levetiracetam, 10 patients continued treatment with good tolerability for 12-38 months 8
• 93% of critically ill patients treated with levetiracetam for acute seizures had no subsequent seizures in one study 4
• Some patients with liver disease showed normalization or improvement in transaminase levels during levetiracetam treatment 8

Important Considerations and Pitfalls

• Seizures in hepatic encephalopathy can increase intracranial pressure and cause cerebral hypoxia, worsening outcomes if not promptly treated 3, 1
• Brain CT imaging should be performed to exclude other causes of decreased mental status, though it has limited utility in identifying early cerebral edema 1
• Hepatic encephalopathy should be considered in patients with previously well-controlled seizures that suddenly become refractory to anticonvulsant therapy 5
• Rare cases of fulminant liver failure have been reported with combined carbamazepine and levetiracetam treatment, suggesting caution with certain drug combinations 9