Lactulose is a synthetic, non-absorbable disaccharide used primarily to manage complications associated with chronic liver disease. It is composed of fructose and galactose, but the human small intestine cannot break it down. This unique structure allows the substance to travel mostly unchanged through the upper digestive tract. Lactulose is used to prevent and treat conditions that arise when the liver cannot fully remove toxic substances from the bloodstream, focusing on neutralizing a specific gut-generated toxin before it affects the brain.
What is Lactulose and How Does it Work?
Lactulose is not digested or absorbed in the small intestine. It passes directly into the large intestine, where resident gut bacteria metabolize it. This breakdown produces smaller organic compounds, primarily lactic acid and short-chain fatty acids.
The resulting organic acids significantly lower the pH level inside the colon. This acidic environment facilitates the conversion of ammonia (\(\text{NH}_3\)) into the ammonium ion (\(\text{NH}_4^+\)). Ammonia is a neurotoxin produced by intestinal bacteria during protein breakdown, which a healthy liver normally processes.
This conversion process is called ion trapping. The highly absorbable, neutral ammonia gas is turned into the non-absorbable, positively charged ammonium ion. The electrical charge prevents the ammonium ion from passing through the intestinal lining and entering the bloodstream. The trapped ammonium is then expelled from the body through the stool.
Lactulose also acts as an osmotic laxative due to its metabolites. The short-chain fatty acids draw water into the colon, resulting in softer stool and increased bowel movement frequency. This cathartic action speeds up the physical elimination of the trapped ammonium and other nitrogenous waste products.
Treating Hepatic Encephalopathy
Lactulose is primarily used to treat Hepatic Encephalopathy (HE), a neurological disorder affecting people with advanced liver disease. HE results from the liver’s failure to adequately clear toxins, especially ammonia, from the blood. When the liver is damaged, ammonia bypasses it and enters the systemic circulation, reaching the brain where it causes neurotoxicity.
HE symptoms range from subtle cognitive impairment (minimal HE) to obvious signs like confusion, personality changes, and impaired motor skills. Severe, overt HE can progress to stupor and coma. Lactulose targets the root cause of these neurological symptoms by reducing the concentration of ammonia in the blood.
By trapping ammonia as ammonium in the colon and promoting rapid excretion, lactulose interrupts neurotoxin accumulation. Lactulose therapy can reduce blood ammonia levels by 25% to 50%, correlating with improved mental status. The goal is to reduce the severity of acute episodes and prevent recurrence, improving cognitive functions and overall quality of life.
Administration, Monitoring, and Side Effects
Lactulose is most commonly administered as an oral liquid syrup. It can also be given via a nasogastric tube or rectally in emergency situations. For acute HE episodes, a high dose is given frequently until a bowel movement occurs to rapidly clear trapped toxins. If a patient is comatose or at high risk of aspiration, a lactulose solution mixed with water can be administered as a retention enema.
Lactulose dosing is unique because it is titrated to a specific clinical outcome rather than a fixed amount. Healthcare providers adjust the dose to ensure the patient has approximately two to three soft bowel movements daily. This target frequency ensures efficient removal of ammonium ions without causing excessive diarrhea. Monitoring bowel movement frequency and consistency is an integral part of therapy.
Patients should be aware of potential side effects, especially during the initial treatment phase. Common adverse effects are gastrointestinal, including abdominal bloating, flatulence, and cramping caused by the fermentation of the sugar. Diarrhea is a frequent side effect; if severe, it indicates the dosage is too high and must be reduced. Excessive diarrhea can lead to fluid loss and electrolyte imbalances, such as low potassium levels.