What is hepatic encephalopathy?
Hepatic encephalopathy is a neurological manifestation of acute liver failure, often in patients with decompensated cirrhosis. It is associated with long-standing cognitive problems that worsen with each episode.
Pathophysiology
The pathophysiology is not fully understood, but in summary, ammonia (and other toxins) that are normally metabolized by the liver accumulate in the serum. When they reach the brain, they increase glutamine production, causing cerebral edema and encephalopathy. Cerebral edema and encephalopathy are worsened by inflammation, hemodynamic instability, and hypotension.
What are the precipitants of hepatic encephalopathy?
- Increased nitrogen: GI bleeding, infection.
- Decreased elimination of toxins: kidney failure, constipation, lack of adherence to medications.
- Alteration of neurotransmitters: alcohol, sedatives, hypoglycemia, hypoxemia.
What about dietary protein intake?
A high-protein diet can increase nitrogen levels that contribute to hepatic encephalopathy. However, the evidence for limiting protein in the diet is not strong and the review articles we consulted had different opinions on this practice. It is important to note that patients with cirrhosis may also be at risk for sarcopenia , so it is important to optimize nutritional status.
How do patients present?
Hepatic encephalopathy is classified on a scale, where a higher grade corresponds to a worse prognosis.
|
Key story points
Hepatic encephalopathy is a diagnosis of exclusion . Rule out other causes of altered mental status: medications, substances, withdrawal, sepsis, kidney failure, head trauma.
- Determine the probable etiology of liver disease.
- Ask about the patient’s baseline health and neurological status.
- Assess chronic management: most recent endoscopy, weight, medications, medication adherence, average number of bowel movements per day.
- Ask about previous complications: infections, varicose veins, encephalopathy.
Detection of a cause of decompensation : infectious symptoms, gastrointestinal bleeding, constipation, urinary symptoms, transjugular intrahepatic portosystemic shunt (TIPS) procedure .
How is asterixis evaluated ?
| Editor’s note : Asterixis or flapping tremor is the most characteristic neuromuscular disorder of hepatic encephalopathy, although it is not pathognomonic and may be absent in advanced stages of the disease. It consists of a fluttering tremor that appears mainly at the level of the wrists. |
Maneuver
You may ask the patient to extend their arms with wrists extended and fingers spread. They will be unable to maintain tone in their wrists, resulting in brief, involuntary, irregular, and asynchronous downward movements. This can be much more subtle than the dramatic “hand flapping” described in textbooks.
What about an ammonia level?
Ammonia levels are not indicated for the diagnosis of hepatic encephalopathy. Ammonia will normally be elevated in liver disease due to decreased clearance. Management in the emergency environment will not change.
Choosing Wisely Canada states: “Do not order serum ammonia to diagnose or manage hepatic encephalopathy (HE). “High blood ammonia levels alone do not add any diagnostic, staging, or prognostic value in HD patients known to have chronic liver disease . ”
What is the initial management of hepatic encephalopathy?
- As always, handle ABC. Altered mental status and hematemesis from variceal hemorrhage are important considerations.
- Assess for focal neurologic signs, signs of trauma, or other indications for head CT. Perform a detailed neurological examination, including the presence of asterixis .
- If ascites with drainable fluid collection is present, perform a paracentesis to rule out SBP.
- Consider whether antibiotics are required for prophylaxis of spontaneous bacterial peritonitis (SBP) or other infection.
- Consider empiric treatment of Wernicke encephalopathy: thiamine 500 mg IV.
- Begin specific treatment for suspected hepatic encephalopathy (discussed later).
Supportive care : Correct fluid, electrolyte, and glucose deficits. Potassium is particularly important. Even mild hypokalemia can decrease ammonia excretion, so correcting hypokalemia is thought to reduce ammonia levels in patients with hepatic encephalopathy.
Avoid long-acting sedative and deliriogenic medications.
Which is the treatment?
Lactulose is the first line for stimulating bowel movements (although more recent evidence suggests that PEG3350 may be superior). It is administered orally at a dose of 10 to 30 g (15 to 45 ml) every 1 to 2 hours until there is a bowel movement.
In patients who cannot tolerate oral medication, enemas are possible. After achieving a bowel movement, continue lactulose 2 to 4 times daily with the goal of achieving 3 to 4 bowel movements per day.
Rifaximin is a non - absorbable antibiotic. It is used as a second line or in combination with lactulose. Emerging evidence suggests that rifaximin monotherapy is superior to lactulose monotherapy. Currently this medication is used as maintenance therapy in patients with recurrent hepatic encephalopathy.
Neomycin has also been studied and is as effective as lactulose, but is rarely used due to its nephrotoxicity, ototoxicity, and neurotoxicity.
What are the complications to take into account?
Intracranial hypertension (ICH) can occur if cerebral edema is not treated. Signs of ICH are systolic hypertension, bradycardia, and irregular breathing. Similarly, seizures can be seen in these patients.
What is the prognosis?
Unfortunately, the prognosis for hepatic encephalopathy is very poor . After a first episode, the 1-year survival rate is only 35-45%.
Provision
Patients with grade 1 hepatic encephalopathy who respond to initial treatment and have support at home can be discharged with outpatient follow-up. However, most patients with grade 1 or 2 HE will require admission. Grade 3 or 4 patients require ICU level care.
