Lactulose is a synthetic sugar, a disaccharide of fructose and galactose, that the human body cannot digest or absorb in the small intestine. This allows it to pass into the colon largely unchanged. The primary medical purpose of this non-absorbable sugar is to manage elevated blood ammonia levels, a condition most commonly associated with severe liver disease. By changing the chemical environment of the gut, lactulose effectively targets the source of ammonia production and absorption, making it a standard treatment for a serious complication that affects brain function.
Understanding Excess Ammonia and Hepatic Encephalopathy
Ammonia (\(\text{NH}_3\)) is a neurotoxin continuously produced in the body, primarily in the gastrointestinal tract. This compound is a byproduct of protein and amino acid breakdown, largely facilitated by bacteria in the colon that possess the enzyme urease. Normally, the liver acts as the body’s detoxification center, converting this toxic ammonia into urea, which is then safely excreted by the kidneys.
When advanced liver disease, such as cirrhosis, severely impairs the liver’s function, this conversion process fails to keep pace with ammonia production. Blood may also bypass the liver entirely through alternative circulation pathways, allowing ammonia to accumulate in the systemic blood. Elevated ammonia levels are dangerous because the compound can cross the blood-brain barrier.
Once ammonia enters the brain, it disrupts normal neurotransmitter function and can cause brain swelling. This neurological syndrome is known as Hepatic Encephalopathy (HE). Symptoms of HE can range from mild confusion and subtle personality changes to severe disorientation, coma, and even death.
The Mechanism of Ammonia Reduction
Lactulose lowers ammonia through a coordinated, three-part mechanism that begins once the unabsorbed sugar reaches the large intestine. First, colonic bacteria ferment the lactulose, breaking it down into smaller, acidic compounds, primarily lactic acid and acetic acid. The production of these acids significantly lowers the pH of the colon’s contents.
This acidification triggers the second effect, known as “ion trapping.” In this low-pH environment, the toxic, uncharged ammonia (\(\text{NH}_3\)) readily accepts a proton (\(\text{H}^+\)) and converts into the charged ammonium ion (\(\text{NH}_4^+\)). Unlike ammonia, the ammonium ion cannot easily pass back through the intestinal wall and into the bloodstream, trapping it within the colon.
The resulting concentration gradient also encourages ammonia circulating in the blood to diffuse back into the colon, where it is similarly trapped. The third effect is the laxative action of lactulose, which is an osmotic agent that draws water into the colon. This speeds up the movement of intestinal contents through the gut. This accelerated transit ensures the rapid expulsion of the trapped ammonium ions via the feces, preventing their reabsorption.
Dosage and Treatment Monitoring
Lactulose is typically administered as an oral solution, but it can also be given rectally as an enema in cases of severe Hepatic Encephalopathy or when oral administration is not possible. Treatment is monitored by observing the patient’s clinical response and bowel movements, rather than blood ammonia levels. The desired therapeutic effect is achieved when the patient has two to three soft stools each day.
For an acute episode of Hepatic Encephalopathy, treatment begins with a high initial loading dose, often 30 to 45 milliliters every one to two hours, until the patient has at least two soft bowel movements. Once the acute phase resolves, the dose is titrated to achieve the maintenance target of two to three soft stools daily. This involves adjusting the amount and frequency of the syrup, typically 30 to 45 milliliters three to four times a day, to maintain the desired consistency and frequency.
Common and Serious Side Effects
The mechanism of action in the colon results in several common side effects, which are generally manageable and often diminish with continued use. These frequently include abdominal cramping, bloating, flatulence, and diarrhea. Diarrhea is an intended side effect, as it is the means of expelling the trapped ammonia.
However, if diarrhea becomes excessive or persistent, it can lead to serious complications requiring immediate medical attention. High-volume diarrhea increases the risk of significant dehydration, with signs including decreased urination or dark, concentrated urine. Prolonged fluid loss can also cause an imbalance in electrolytes, particularly low potassium levels (hypokalemia). Signs of a serious electrolyte disturbance include muscle cramps, weakness, or an irregular heartbeat.