Is lactulose (a laxative) indicated for elevated ammonia levels (hyperammonemia)?

From the Guidelines

Lactulose is recommended for a patient with an elevated ammonia level of 79, with a standard dosing of 25 mL orally every 1-2 hours until at least two soft or loose bowel movements per day are produced, then titrated to maintain two to three bowel movements per day. The goal of lactulose therapy is to create an acidic environment in the colon that converts ammonia (NH3) to ammonium (NH4+), which cannot be reabsorbed and is excreted in stool, thereby reducing blood ammonia levels 1. It is essential to note that the dosing of lactulose should be titrated to achieve the desired effect, and overuse can lead to complications such as aspiration, dehydration, hypernatremia, and severe perianal skin irritation 1.

Some key points to consider when using lactulose include:

• The initial dosing should be 25 mL orally every 1-2 hours until at least two soft or loose bowel movements per day are produced 1
• The dosing should be titrated to maintain two to three bowel movements per day 1
• Patients should be monitored for dehydration and electrolyte imbalances, especially with higher doses 1
• Adequate fluid intake should be maintained while on lactulose therapy 1
• Rifaximin can be used as an add-on therapy to lactulose for prevention of overt hepatic encephalopathy (OHE) recurrence 1

According to the most recent guidelines, empiric therapy with lactulose should be started if no obvious alternative cause is immediately apparent, and the goal is to ensure improved mental status with careful monitoring of electrolytes to prevent dehydration and hypernatremia 1.

From the FDA Drug Label

Controlled studies have shown that lactulose solution therapy reduces the blood ammonia levels by 25 to 50%; this is generally paralleled by the improvement in the patients’ mental state and by an improvement in EEG patterns. Lactulose causes a decrease in blood ammonia concentration and reduces the degree of portal-systemic encephalopathy.

Lactulose may be effective in reducing blood ammonia levels.

• Reduction in ammonia levels: 25 to 50% reduction in blood ammonia levels has been observed in controlled studies 2.
• Clinical response: The clinical response has been observed in about 75% of patients 2. Since the patient's ammonia level is 79, lactulose may help reduce this level, but the exact reduction cannot be predicted. 2

From the Research

Lactulose for Ammonia Levels

• Lactulose is a nonabsorbable disaccharide used to treat hyperammonemia in patients with liver failure 3.
• It works by increasing the elimination and reducing the absorption of ammonia in the gut 4.
• The standard treatment for acute hepatic encephalopathy (HE) is lactulose, but the rate of recurrent HE on maintenance lactulose is high 4.

Efficacy of Lactulose

• Studies have shown that lactulose is effective in reducing ammonia levels and alleviating symptoms of HE 3, 4.
• However, one study found that ammonia levels do not guide clinical management of patients with HE, and lactulose dose is not correlated with ammonia level 5.
• Another study found that combination therapy of lactulose and rifaximin is more effective than lactulose alone in treating overt HE 6.

Comparison with Other Treatments

• Rifaximin is a poorly absorbed antibiotic that reduces ammonia production by eliminating ammonia-producing colonic bacteria 4.
• A study found that rifaximin plus lactulose is more effective than lactulose alone in reducing the risk of recurrent HE 4.
• However, another study found that lactulose only is more effective than lactulose and rifaximin in improving neurological status and reducing mortality 7.

Ammonia Level of 79

• There is no specific study that mentions an ammonia level of 79, but a study found that patients with elevated ammonia levels (>72 μmol/L) did not receive more aggressive lactulose therapy than patients with normal ammonia levels 5.