Liver Encephalopathy - Treatment

Treatment of hepatic encephalopathy can be divided into three main points:

1. Identification and elimination of factors contributing to the development of hepatic encephalopathy.
2. Measures aimed at reducing the formation and absorption of ammonia and other toxins formed in the colon. These include reducing the amount and modification of dietary proteins, changing the intestinal microflora and the intestinal environment.

Treatment of hepatic precoma and coma

Acute hepatic encephalopathy:

1. Factors that contribute to the development of encephalopathy are identified.
2. Cleanse the intestines of nitrogen-containing substances:
   1. stop rotting
   2. do a phosphate enema
3. A protein-free diet is prescribed and, as the patient recovers, the protein content in the diet is slowly increased.
4. Prescribe lactulose or lactitol
5. Neomycin is prescribed orally at 1 g 4 times a day for 1 week.
6. Maintains caloric intake, fluid intake and electrolyte balance
7. Diuretics are discontinued and serum electrolyte levels are monitored.

Chronichepatic encephalopathy:

1. Avoid using nitrogen-containing drugs
2. They limit the protein content in food to the tolerable limits - about 50 g per day, recommending to consume mainly plant proteins
3. Ensure bowel movements at least twice a day
4. Prescribe lactulose or lactitol
5. If the condition worsens, they switch to treatment used for acute encephalopathy of the environment (antibiotics, lactulose or lactitol), stimulation of emptying of the colon (enemas, lactulose or lactitol).
6. Prescription of drugs that modify the ratio of neurotransmitters directly (bromocriptine, flumazemil) or indirectly (branched-chain amino acids). At present, these methods are rarely used in clinical practice.

The choice of treatment method depends on the clinical picture: subclinical, acute or persistent chronic encephalopathy

Diet

In acute hepatic encephalopathy, the amount of dietary proteins should be reduced to 20 g per day. The caloric content of food is maintained at 2000 kcal per day or higher when taken orally or by parenteral nutrition.

During recovery, the protein content is increased by 10 g every other day. If encephalopathy relapses, the previous level of protein in food is returned. In patients recovering from an acute episode of coma, the protein content in food is soon brought to normal. In chronic encephalopathy, patients must constantly limit the amount of dietary protein to avoid the development of psychopathological symptoms. The usual protein content in food is 40-60 g per day.

Vegetable proteins are better tolerated than animal proteins. They have a lower ammoniogenic effect and contain little methionine and aromatic amino acids. In addition, vegetable proteins have a more pronounced laxative effect, and their use increases the intake of dietary fiber; this leads to increased binding and excretion of nitrogen contained in the bacteria of the colon. Intake of plant foods may be difficult due to the development of flatulence, diarrhea, and bloating.

In acute cases, it is possible to completely exclude proteins from the diet for a period of several days to several weeks - this will not cause harm to the patient. Even in chronic encephalopathy, in patients whose consumption of dietary proteins has been limited for many months, clinical signs of protein deficiency are rarely encountered. Protein restriction is indicated only for patients with signs of encephalopathy. In other cases of liver disease, a high-protein diet can be successfully prescribed; this is achieved by the simultaneous use of lactulose or lactitol.

Antibiotics

Neomycin administered orally successfully reduces the formation of nitrogen compounds in the intestine. Although only a small amount of this drug is absorbed from the intestine, it can be detected in the blood of patients, so long-term use of neomycin can lead to hearing loss or deafness. It should be prescribed only in acute cases at 4-6 g / day in several doses for 5-7 days. However, it is difficult to associate the improvement in the clinical condition of patients with changes in fecal microflora.

Metronidazole 200 mg 4 times daily orally appears to be as effective as neomycin. It should not be used for long periods because of dose-dependent CNS toxicity. In acute hepatic coma, lactulose is given, and if its action is slow or incomplete, neomycin is added. The two drugs are synergistic, probably because they act on different groups of bacteria.

Lactulose and lactitol

The human intestinal mucosa does not contain enzymes that break down these synthetic disaccharides. When taken orally, lactulose reaches the cecum, where it is broken down by bacteria to form predominantly lactic acid; the pH of the stool decreases. This promotes the growth of lactose-splitting bacteria; the growth of ammoniogenic microorganisms such as bacteroides is inhibited. Lactulose can "detoxify" short-chain fatty acids formed in the presence of blood and proteins. In the presence of lactulose and blood, colonic bacteria primarily break down lactulose. This is of particular importance in hepatic encephalopathy caused by bleeding. When lactulose is administered, the osmotic pressure in the colon increases.

The mechanism of action of this drug is not precisely known. An acidic reaction of the feces may reduce the ionization and, therefore, the absorption of ammonia, as well as amines and other toxic nitrogen-containing compounds; however, the ammonia content in the feces does not increase. In the colon, lactulose more than doubles the formation of bacteria and soluble nitrogen compounds. As a result, nitrogen is not absorbed as ammonia and the formation of urea is reduced.

When prescribing lactulose, one should strive to form acidic feces without diarrhea in the patient. The drug is prescribed in a dose of 10-30 ml 3 times a day, which leads to a double bowel movement of semi-liquid feces.

Efficacy of lactitol compared to lactulose

• Similar action in the colon
• It is equally effective in hepatic encephalopathy.
• Acts faster
• More convenient to use (powdered)
• Less sweet
• Less likely to cause diarrhea and flatulence

Side effects include flatulence, diarrhea, and intestinal pain. Diarrhea can be so severe that the serum sodium level exceeds 145 mmol/l, the potassium level decreases, and alkalosis develops. The circulating blood volume decreases, resulting in impaired renal function. Such complications develop especially often if the daily dose of the drug exceeds 100 ml. Some side effects may be associated with the admixture of other sugars in lactulose syrup. Crystalline lactulose may be less toxic.

Lactitol (beta-galactosidic sorbitol) is a second-generation disaccharide. It is easily obtained in chemically pure crystalline form, from which powder can be prepared. This preparation is not inactivated or absorbed in the small intestine, but is broken down by bacteria in the colon. Powdered lactitol is more convenient to use than liquid lactulose and can be used as a sugar substitute. It tastes better and is less cloying. The daily dose is approximately 30 g.

Lactitol is as effective as lactulose in treating chronic and acute portosystemic encephalopathy. Lactitol acts faster than lactulose and causes less diarrhea and flatulence.

Lactulose and lactitol are used to treat subclinical hepatic encephalopathy. Their use improves the results of psychometric tests. At a dose of 0.3-0.5 g/kg per day, lactitol is well tolerated by patients and is quite effective.

Bowel cleansing with laxatives. Hepatic encephalopathy develops against the background of constipation, and remissions are associated with the resumption of normal bowel function. Therefore, in patients with hepatic encephalopathy, special attention should be paid to the role of enemas and bowel cleansing with magnesium sulfate. Enemas with lactulose and lactose can be used, and after them - with clean water. All enemas should be neutral or acidic to reduce the absorption of ammonia. Enemas with magnesium sulfate can lead to hypermagnesemia, which is dangerous for the patient. Phosphate enemas are safe.

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