Seizures in Hepatic Encephalopathy

• Seizures have traditionally been viewed as a rare event in hepatic encephalopathy
• Overall incidence of seizures in hepatic encephalopathy varies between 2% and 33%
• Seizure activity has been reported in previous clinical series of acute liver failure and is a well-recognized complication of acute hyperammonemia in urea-cycle disorders
• Non-convulsive status epilepticus may be particularly common in these patients

Treatment

• Absolute data for safety profile of drugs in liver disease is still not clear, as changes of pharmacokinetics make choice of drugs difficult.
• Free drug concentrations may be higher, making plasma concentration monitoring essential in such circumstances.
• A single seizure may not require therapy. However when started, antiepileptic drugs are usually discontinued early.
• Drugs with sedative effects are best avoided because of a risk of precipitating coma.
• Phenytoin and gabapentin are relatively preferred drugs; however, monitoring of drug levels is desirable.

Evidences

• the use of phenytoin was shown to significantly reduced seizure frequency and the development of increased ICP
• In a recent controlled trial, subclinical seizure activity was detected in 10 of 22 patients enrolled as controls in a trial of prophylactic phenytoin in ALF. At autopsy, patients in the nontreated group had greater evidence of cerebral edema

Safety of Phenytoin

• Is highly protein bound (90%), primarily binding to albumin
• Elimination occurs chiefly through hepatic microsomal biotransformation
• In hepatic insufficiency, presence of low albumin/reduced binding capacity may lead to higher drug levels and potential toxicity
• Nonlinear kinetics and difficulty in estimating hepatic metabolic capacity limits the ability to predict dose adjustment

Management of agitation

• includes physical restraint and medication.
• Benzodiazepines are best avoided.
• Haloperidol is a safer choice in the presence of liver disease

References:

1. http://www.medscape.com/viewarticle/463473_2
2. http://www.ncbi.nlm.nih.gov/pubmed/15025257
3. http://www.ncbi.nlm.nih.gov/pubmed/17190918
4. http://www.hindawi.com/journals/ijh/2011/841407/
5. Management of agitation and convulsions in hepatic encephalopathy. Indian society of Gastroenterology
6. Hepatic encephalopathy with status epileptics: A case report. World J Gastroenterol 2006 March 21; 12(11): 1793-1794