Friday, June 3, 2016

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

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